top stories 3 and clinical trials 7 awarded 13 grant news ...ly, obstructive mgd is due to terminal...

SSF Medical and Scientific Advisory Board

ChairElaine Alexander, MD, PhD, FACR*

MembersRichard Brasington, MD, FACRSteven E. Carsons, MD*Troy Daniels, DDS, MS*H. Kenneth Fisher, MD, FACP, FCCPGary Foulks, MD, FACSPhilip C. Fox, DDS*Tara Mardigan, MS, MPH, RDAustin Mircheff, PhDJohn Daniel Nelson, MD, FACSKelly Nichols, ODAthena Papas, DMD, PhDAnn Parke, MDAndres Pinto, DMDNelson Rhodus, DMD, MPHDaniel Small, MD, FACPNeil Stahl, MDPamela Stratton, MDFrederick B. Vivino, MD, FACR

Associate MembersSimon J. Bowman, PhD, FCRPRobert I. Fox, MD, PhD, FACP*Arthur Grayzel, MD, FACR*Roland Jonsson, DMD, PhDStuart S. Kassan, MD, FACP*Robert Lebovics, MDMichael Lemp, MD*Xavier Mariette, MDHaralampos M. Moutsopoulos, MD*James J. Sciubba, DMD, PhD*Janine A. Smith, MDHarry Spiera, MD*Leo Sreebny, DDS, MS, PhD*Norman Talal, MD*Athanasios G. Tzioufas, MDIra J. Udell, MD*Claudio Vitali, MDDaniel J. Wallace, MDPierre Youinou, MD, Dsc

*Counselor

Sjögren’sQuarterly

Sjögren’s Syndrome Foundation6707 Democracy Blvd., Ste 325Bethesda, MD 20817(301) 530-4420

www.sjogrens.org©2011 Sjögren’s Syndrome Foundation

Vol. 6, Issue 4 – Fall 2011 The Professionals’ Resource on Sjögren’s Syndrome

Research in Type 1 Diabetes Points to Potential for New Sjögren’s Treatment

Top Stories 3GrantNewsinGenetics andClinicalTrials

7SSFResearchGrants Awarded

13OralHealthand EducationNews

15PatientEducation– MuscleandJointPain

Continued on page 2 t

Denise L. Faustman, MD, PhD

treating Patients with Meibomian Gland Dysfunction — Progress toward a Better understandingby Kelly K. Nichols, OD, MPH, PhD, FERV Professor (Foundation for Education and Research in Vision), University of Houston, College of Optometry, Houston, Texas

Meibomian Gland Dysfunction (MGD) is an extremely important condition, conceivably underesti-

mated and very likely the most frequent cause of dry eye disease. MGD may be the most common cause of evaporative dry eye and also have an association with aqueous-deficient dry eye, both conditions of which are associated with Sjögren’s syndrome. This article will dis-cuss the most up-to-date information on MGD and how clinicians should approach diagnosis and management of this common problem.

As reported in the Spring 2011 issue of the Sjögren’s Quarterly by Dr. Nichols and Gary Foulks, MD, FACS, the long-awaited Meibo-mian Gland Report was released and published this spring.1,2 Based on a workshop supported by the Tear Film and Ocular Surface Society (TFOS), this major report follows on the heels of the 2007 Report of the International Dry Eye

In type 1 diabetes, the low-cost, generic drug Ba-cillus Calmette-Guérin, most commonly known as BCG, is currently being developed as a poten-

tial disease-reversal treatment at Massachusetts Gen-eral Hospital (MGH) and Harvard Medical School. In the Phase I human clinical trial, BCG vaccination – which is known to be safe and is commonly used around the world in the prevention of tuberculo-sis – was shown to eliminate the autoreactive T cells responsible for the attack on the pancreas. It also temporarily restored insulin production in the trial participants, strongly suggesting regeneration of the pancreas – at least while the autoimmune attack was held in check by the vaccination.

by Denise L. Faustman, MD, PhD, Associate Professor of Medicine, Harvard Medical School, Charlestown, Massachusetts


EditorKatherine M. Hammitt, MA

Medical & Scientific EditorSteven Carsons, MD

Co-Medical & Scientific EditorsPhilip C. Fox, DDS

Austin Mircheff, PhD

At-Large Medical & Scientific ReviewersElaine Alexander, MD, PhD, FACRRichard Brasington, MD, FACP

Nancy Carteron, MD, FACRStuart Kassan, MD, FACP

Frederick B. Vivino, MD, FACR

SSF CEOSteven Taylor

e-mail: [email protected]

The Sjögren’s Quarterly® newsletter is published by the Sjögren’s Syndrome Foundation Inc.,

6707 Democracy Blvd., Ste 325, Bethesda, MD 20817. Copyright ©2011 Sjögren’s Syndrome

Foundation Inc. ISSN 0899-637.

DISCLAIMER: The Sjögren’s Syndrome Foundation Inc. in no way endorses any of the medications, treatments, or products mentioned in advertisements or articles.

“Clinician’s Corner” Continued from page 1 t


Workshop (DEWS), also sponsored by TFOS. These two reports together mark major advances in awareness, understanding, diagnosis and treat-ment of dry eye and the MGD which can accompany dry eye in Sjögren’s patients. More than 50 experts par-ticipated in the International Work-shop on Meibomian Gland Dysfunc-tion over a two-year period.

Definition and terminology The committee proposed the following definition of MGD: “Meibo-

mian gland dysfunction is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation and ocular surface disease.”3

Part of the challenge with previous clinical research and publications in this area has been inconsistency in terminology. To unify the field, the work-shop had to review and agree upon its terminology. First, the term “dysfunc-tion” was used because the overall function of meibomian glands is altered. The term “diffuse” was chosen because the disorder involves most of the meibomian glands rather than isolated glands (e.g. hordeola or chalaziia).

Obstruction of the meibomian gland orifices and terminal ducts and qualitative and/or quantitative changes in meibomian gland secretions were identified as the most prominent aspects of MGD. In addition, sub-jective symptoms of eye irritation were included in the definition because the symptoms are of greatest concern to the patient and often the clinician. Improvement in patient symptoms is the major goal of MGD treatment.

Additional terms warranting discussion include “posterior blepharitis”— often referred to as synonymous with MGD. Posterior blepharitis is a term

used to describe inflammatory conditions of the posterior lid margin, of which MGD is only one cause. In its earliest stages, MGD may not be associated with clinical signs characteris-tic of posterior blepharitis. The role of inflammation in the etiology of MGD is controver-sial and uncertain.

In early stages of MGD, patients may be symptomatic, but alternatively they may be asymptomatic and termed

subclinical. As MGD progresses, additional symptoms develop as well as lid margin signs, such as changes in meibum expressibility and quality, and lid margin redness/edema. At this point, MGD-related posterior blepharitis is said to be present. Ultimately, MGD can lead to alterations of the tear film, symptoms of eye irritation, inflammation and dry eye.

Diagnosis Of greatest interest to the clinician is the diagnosis and management of

MGD. The diagnosis of MGD—whether in isolation or associated with ocu-lar surface damage or dry eye—should be viewed in the context of diagnosing any ocular surface disease in a medically-oriented ocular surface examination.

Diagnostic tests include gland expression to evaluate the quality and quan-tity (availability) of meibomian gland secretions. Digital pressure on the lower lid for approximately 15 seconds in duration with a slight rolling upward of the cotton swab or finger tip usually results in expression of meibomian gland

Kelly K. Nichols, OD, MPH, PhD

A complete dry eye examination should include symptom evalu-ation, clinical assessment of the meibomian glands, meibomian gland expressibility and evalua-tion of the quality of meibomian gland secretions. Co-existing dry eye should be evaluated through assessment of tear film instability and ocular surface staining.

2 Sjögren’s Quarterly

OMrF receives Major NIH Grant to Create research Center for Sjögren’s

The Oklahoma Medical Research Foundation (OMRF) has received a five-year $7.8 million grant from the National Institute of Arthritis and Muscu-loskeletal and Skin Diseases (NIAMS) at the National Institutes of Health. The funds will be used to create the Oklahoma Sjögren’s Syndrome Center of Research Translation which will focus on developing new ways to diagnose and treat Sjögren’s. The center will be headed by SSF Research Grantee Kathy Moser, PhD.

The grant will fund three key research initiatives:

Kathy Moser, PhD will use state-of-the-art DNA scan-ning technology to pinpoint the genes associated with Sjögren’s.

Darise Farris, PhD will study how interfering with the regulation of T cells in the immune system leads to the development of Sjögren’s.

Hal Scofield, MD will char-acterize how B cells in the salivary glands play a role in disrupting moisture-produc-ing mechanisms.

“OMRF is already a world leader in Sjögren’s research, and this grant allows us to continue important work on finding the causes and potential treatments for the disease,” says Dr. Moser, who serves as primary investigator on the grant and director of the OMRF Sjogren’s Research Center. “We’ll be using new technology to make inroads on questions that have been asked about this disease for

decades.”It takes an average of almost 10 years for patients with

Sjögren’s syndrome to be diagnosed because of a lack of awareness and good diagnostic tests for the disease, said Moser. “The better we understand Sjögren’s, the better we can diagnose it and the faster we can start treating pa-tients.” n

two additional u.K. Centers launch Clinical trials for rituximab in Sjögren’s

Medical centers in Cambridge and London have joined Birmingham in the United Kingdom in con-ducting clinical trials in Sjögren’s using the chimeric anti-CD20 monoclonal antibody rituximab (Rituxan®). In the Winter 2011 issue of the Sjögren’s Quarterly, we reported that Simon Bowman, PhD, FCRP had received a £1 million grant from a medical research charity to launch a Phase 3 trial in Sjögren’s. That charity, Arthri-tis Research UK, has now awarded a £43,000 grant to two additional centers to expand the investigation into rituximab as a potential therapy for Sjögren’s patients.

The latest 2-year grant goes to Dr. Frances Hall, lec-turer in rheumatology at the University of Cambridge and consultant at Addenbrooke’s Hospital, Cambridge, and her colleagues, senior researchers Dr. Paul Lyons and Dr. Robert Busch, and Dr. Michele Bombardieri, senior lecturer and consultant at Queen Mary, Univer-sity of London. Dr. Hall will compare patients’ T cells before and after treatment with rituximab to determine how the T cells react to the depletion of B cells and whether the T cell reaction helps the mechanism of the treatment. She also will look at the activity of genes in patients’ T cells which could lead to the identification of novel biomarkers.

Dr. Bowman already has launched a multi-trial center in collaboration with Dr. Paul Emery at Leeds University and Dr. Costantino Pitzalis of Queen Mary, University of London. Many of the patients also come from a register funded by the Medical Research Council and set up by colleague Dr. Wan-Fai Ng in Newcastle. n

Grant News in Genetics and Clinical trials

Hal Scofield, MD

Kathy Moser, PhD

Darise Farris, PhD

Sjögren’s Quarterly 3

ly, obstructive MGD is due to terminal duct obstruction. In the cicatricial form, the duct orifices are dragged pos-teriorly into the mucosa, whereas these orifices remain in their normal position in non-cicatricial MGD.

anatomy, Physiology and Pathophysiology The meibomian glands are large sebaceous glands

located in the tarsal plates of the eyelids, and their job is to secrete the lipids critical to maintaining the stabil-ity of the tear film. Each meibomian gland consists of multiple secretory acini containing meibocytes, lateral ductules, a central duct and a terminal excretory duct that opens at the posterior lid margin. There are more glands in the upper lid; the relative functional contribu-tion of the upper and lower lid glands to the tear film and the method of lipid delivery to the tear film remain to be determined.7

The glands are regulated by androgens, estrogens, progestins, retinoic acid and growth factors, and pos-sibly by neurotransmitters. The exact components of meibum include a complex mixture of various polar and non-polar lipids containing cholesterol and wax esters, diesters, triacylglycerol, free cholesterol, free fatty acids and phospholipids, yet some of the differences in meibum between normal and MGD patients have yet to be fully characterized on a molecular level.

In contrast to the overall thickness of the tear film (roughly 3µm to 40µm), the tear lipid layer thickness is 15nm to 160nm. Tear film lipids also appear to be es-sential for ease and comfort in contact lens wear, despite forming deposits on lenses. Contact lens wear itself may disrupt the meibomian glands and/or lipid layer and lead to tear film evaporation and ocular surface discomfort.8

The primary cause of MGD is terminal duct obstruc-tion with thickened opaque meibum containing kera-tinized cell material. This obstruction is due to hyper-keratinization of the ductal epithelium and increased meibum viscosity. The obstruction may lead to pressure within the gland, meibocyte atrophy, gland dropout and low secretion.

The end result of MGD is reduced availability of meibum to the lid margin and tear film, and the resul-tant instability of the tear film, possibly potentiating bacterial growth on the lid margin, evaporative dry eye, ocular surface inflammation, damage and symptoms.8

epidemiology and associated risk Factors Epidemiology: The reported prevalence of MGD varies

widely, and studies specific to MGD are lacking. In the existing studies, a striking observation is that the preva-lence of MGD appears to be much higher in Asian popu-lations (approaching 65% depending on the method of classification).5 Further studies of prevalence, incidence, natural history and impact on quality of life are needed.

secretions. The glands can then be evaluated for ex-pressibility and meibum quality.4 A diagnosis of MGD may require that the patient be further assessed for symptoms, lid morphologic signs and ocular surface damage (staining). The MGD Workshop has proposed a staging of disease, from asymptomatic to severe.

Management and therapyTreatment of MGD varies greatly among eye care

providers, and data to support any one treatment over the other is limited. In fact, while the most commonly used clinical manuals (The Moorfields Manual of Oph-thalmology and The Wills Eye Manual) cite the same tools for management, the frequency and length of time for a treatment method often varies. A table showing the comparisons between recommended treatments in the manuals is included in the workshop report as well as a Treatment Algorithm based on the graded severity of MGD for reference.

Current standard of care includes:

• Patient education about MGD and its chronic nature

• Cleansing of the lid margins with mild baby shampoo and/or cotton buds

• Warm compress therapy

• Consideration of omega fatty acid supplements (Omega-3), which may be protective5

• Topical azithromycin

• Artificial lubricants (preferred non-preserved for frequent use)

• Topical emollient lubricant or liposomal spray

• Oral tetracyclines

• Meibomain gland therapeutic expression

• Topical cyclosporine for cases with concurrent signifi-cant corneal staining/aqueous dry eye6

A clinician’s complete dry eye examination should include a symptom evaluation, clinical assessment of the meibomian glands, meibomian gland expressibility and evaluation of the quality of meibomian gland secretions. Co-existing dry eye should be evaluated through assess-ment of tear film instability and ocular surface staining.

ClassificationThe workshop proposed that MGD should be clas-

sified into two major categories based on meibomian gland secretion: low delivery states and high delivery states. Low delivery states are further classified as hy-posecretory and obstructive, with cicatricial and non-cicatricial subcategories.

Hyposecretory MGD describes the condition of de-creased meibum delivery due to abnormalities in meibo-mian glands without remarkable obstruction. Important-




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• Cevimeline HCl can potentially alter cardiac conductionand heart rate and produce transient changes inhemodynamics. Cevimeline HCl should be administeredwith caution and under close medical supervision topatients with a history of cardiac disease, controlledasthma, chronic bronchitis, or chronic obstructivepulmonary disease

• Cevimeline HCl should be administered with caution topatients taking beta-adrenergic antagonists because ofthe possibility of conduction disturbances and to patientswith a history of nephrolithiasis or cholelithiasis

• If a patient sweats excessively while taking cevimeline HCl,dehydration may develop

• Caution should be advised while driving at night orperforming hazardous activities in reduced lighting

• Safety and effectiveness in pediatric patients have notbeen established

• Cevimeline HCl is metabolized by the P-450 isozymesCYP2D6 and CYP3A3/4. Thus, there may be potential forinteraction between cevimeline HCl and other compounds

• Special care should be exercised when cevimeline HClis taken by geriatric patients, considering the greaterfrequency of decreased hepatic, renal, or cardiac function

• The most frequently reported adverse events associatedwith the pharmacologic action of a muscarinic agonist(>10% incidence) in clinical trials of cevimeline HCl were:excessive sweating, nausea, rhinitis, and diarrhea. Consultthe full Prescribing Information for other adverse events

Please see next page for brief summary of thefull Prescribing Information about EVOXAC.

References: 1. Fife RS, Chase WF, Dore RK, et al. Cevimeline for the treatment of xerostomia in patients withSjögren syndrome: a randomized trial. Arch Intern Med. 2002;162(11):1293-1300. 2. Petrone D, Condemi JJ,Fife R, Gluck O, Cohen S, Dalgin P. A double-blind, randomized, placebo-controlled study of cevimelinein Sjögren’s syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum.2002;46(3):748-754. 3. EVOXAC [package insert]. Edison, NJ: Daiichi Sankyo, Inc.; November 2006.

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appointment with the pharmacology department at the University of Virginia, Charlottesville, Virginia, which has helped catalyze his interest in Sjögren’s and drug development; presented at the 2010 American College of Rheumatology Sjögren’s Study Group; and authored a lead article for the summer 2011 issue of the Sjögren’s Quarterly. “This is exactly what we like to see happen with all of our foundation grants and especially our In-novative Concept Grants,” says Denise Faustman, MD, PhD and Chair of the SSF Research Review Committee. “In fact, following our continual examination of the best use of SSF funds to support and promote research in Sjögren’s, we will be making all future grants contin-gent on innovation and the Innovative Concept Grant guidelines. It is critical that we bring in new and prom-ising researchers and provide the seed money for novel ideas which often are not fundable from other sources.”

Changes in the 2012 SSF research ProgramIn 2012, the Sjögren’s Syndrome Foundation will

change its grants program to solely focus on funding innovative concepts. As a result, all research grants will be Innovative Concept Grants. The SSF wants to ensure that the limited funding it has to give researchers is used to encourage new investigators to explore novel concepts and provide the data necessary for obtaining additional and major funding from government agen-cies or other funding sources.

Grants will be awarded at $35,000 a year for two years, depending on satisfactory progress, and a human study that reviewers deem to be the most innovative project will be eligible for a $50,000 grant.

2011 Research GranteesSSF Innovative Concept Grant

Gene Therapy for Targeting Salivary Gland Treatment

Michael J. Passineau, PhD, Allegheny-Singer Research Institute, West Penn Allegheny Health System Pittsburgh, Pennsylvania

“Ultrasound-assisted gene transfer of IL17R:Fc to the salivary glands as a gene therapy for Sjögren’s syndrome”

Supported by the Leach Family

The Sjögren’s Syndrome Foundation (SSF) has awarded seven research grants for FY 2011. New projects include a focus on us-

ing a novel approach to making the concept of gene therapy potentially viable; development of a molecu-lar diagnostic test for early Sjögren’s; and examina-tion of potential novel molecular/cellular pathways involved in the etiology of Sjögren’s. All of these projects could lead to new therapeutics in Sjögren’s.

The SSF Innovative Concept Grant was awarded this year for the third time in SSF history. This special grant is not awarded every research grant cycle but is reserved solely for those projects that the SSF Research Review Committee deems highly innovative and will test new hypotheses in the hope that promising data is gathered, will be used to obtain additional funding from other sources for continuation of the project and ultimately will lead to new knowledge about Sjögren’s and poten-tially new therapeutics. This grant also is reserved for in-vestigators early in their career to encourage top-notch researchers to focus on Sjögren’s for years to come.

This year’s Innovative Concept Grant winner was made possible by the Leach Family. This family returns for a second time of funding an Innovative Concept Grant and believes in the premise that we will not accomplish a major breakthrough in treatment of Sjögren’s unless we support the investigators of tomor-row who will think outside the traditional concepts in Sjögren’s research. In addition, the Galewood Founda-tion continued its support this year to assure expansion of the SSF Research Program and funding for top ap-plicants. “The Sjögren’s Syndrome Foundation applauds the Leach Family and the Galewood Foundation for their vision and willingness to support these special investigators,” says SSF CEO Steven Taylor. “Both have made significant contributions to make a difference and promote research into Sjögren’s.”

The Leach Family first supported an Innovative Concept Grantee in 2008 and 2009, Umesh Deshmukh, PhD, who has since successfully pursued research in Sjögren’s. Since the completion of his SSF research grant in 2009, Dr. Deshmukh has received an R21 grant from the National Institutes of Health (NIH); added a second

the SSF announces the 2011 research Grant recipients and Future Changes in award Guidelines



SSF Research Review Committee members stated that Dr. Passineau’s project was a unique, innovative and classic high risk-high reward proposal with the potential for moving a gene therapeutic approach closer to reality for Sjögren’s. The proposal provides a critical proof-of-concept trial.

Scientific AbstractThis research project builds upon several promising

prior studies which have utilized gene therapy as a ther-apeutic strategy for Sjögren’s Syndrome. Gene therapy is a particularly exciting approach to this difficult disease because it can directly target the salivary gland with a gene drug, avoiding the systemic toxicity often seen with traditional pharmaceuticals. The major innova-tion embodied in this project is the application of a new ultrasound-assisted method of gene drug delivery. Prior instances of salivary gland gene therapy, including the first-in-man human clinical trial, have used viral vec-tors as the gene delivery vehicle. These vectors are ideal for proof-of-principle studies but are not practical for long-term therapy. Our ultrasound approach overcomes the drawbacks of viral vectors, and it is hoped that this project will provide a strong rationale for translating this promising technology to higher mammals and ultimately humans.

Adenoviral-mediated gene therapy has shown proof-of-principle efficacy in several animal models of SS, notably a recent study that showed functional and im-munological improvement of SS-prone C57BL/6.NOD-Aec1Aec2 mice using an IL-17R:Fc fusion protein as the therapeutic transgene. In order to make these promising demonstrations practical for SS therapy, a gene delivery method that allows repeated serial re-dosing over the lifetime of the individual is absolutely essential, and currently-available viral vectors (Adeno and AAV) can-not meet this critical criterion. This project proposes to apply ultrasound-assisted gene therapy to deliver the IL-17R:Fc transgene C57BL/6.NODAec1Aec2 and precisely mimic the therapeutic metrics of Nguyen et al. (Editor’s Note: Cuong Nguyen, PhD, is a current SSF re-search grantee whose grant has been renewed for a second year in 2011 and project is included in this article.)

UAGT meets all of the criteria for a practicable, re-dosable gene delivery strategy for chronic salivary gland gene therapy. The studied outlined in this proposal, if successful, will provide a strong rationale for translat-ing this enabling technology to higher mammals and eventually human SS patients.

SSF research Grant

Novel Molecular Mechanisms Underlying SS Pathogenesis

Shen S. Hu, PhD UCLA School of Dentistry, Los Angeles, California

“Interferon-Y induces immunoproteasome in human

salivary gland cells”

SSF reviewer comments included highlighting the critical importance of this area for Sjögren’s research and its clear extension of highly innovative work ac-complished previously by others in the field. Reviewers emphasized the solid and excellent environment, the SSF goal of encouraging another excellent investigator in the early stages of his career to focus on Sjögren’s and the importance of doing human studies in Sjögren’s.

Scientific AbstractDespite its high prevalence, the etiology and patho-

genic mechanisms of Sjögren’s syndrome (SS) remain elusive, suggesting the importance of studying the mo-lecular and cellular mechanisms of the disease. In this project, we aim to understand the role of interferon-gamma and immunoproteasome in primary SS. Our project may facilitate the development of new therapeu-tic strategies for the disease patients.

We recently demonstrated that interferon-gamma (IFN-g) induces immunoproteasome in cultured hu-man salivary gland cells and over-presentation of MHC I-associated peptide on the cell surface. Meanwhile, beta-2-microglobulin was found to be over-expressed in patients with primary SS. Based on these findings, we hypothesize that immunoproteasome is induced by IFN-g in the salivary gland cells of SS patients, leading to over-presentation of MHC-I associated peptides on the cell surface. Salivary gland CD8+ T lymphocytes then recognize the MHC I peptide-presenting cells and cause their death or lysis. This hypothesis will be tested in primary cultured parotid gland cells, and the unique peptides presented on the salivary gland cells of SS will be identified using a mass spectrometry-based approach. We will also investigate if CD8+ T cells cause severe cytotoxicity to MHC I peptidepresenting gland cells. This innovative project may reveal a novel molecu-lar mechanism underlying SS pathogenesis.

SSF research Grant

Identifying an Early Diagnostic Marker in Early Stage Sjögren’s

Melinda Larsen, PhD The Research Foundation of SUNY, University at Albany Department of Biological Sciences, Albany, New York

“Application of Multiplexing Technology to the Study of Sjögren’s Syndrome”

“Research Grants” Continued from page 7 t


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corneal neo-lymphatic vessels which facilitate traffick-ing of mature corneal APC toward the draining lymph nodes. To validate his group’s hypothesis, he proposed three specific aims – Aims 1 and 2 involved confirma-tion and determination of cellular and molecular factors that contribute to lymphangiogenesis in DED cornea, and Aim 3 would test the efficacy of in-vivo blockade of select pro-lymphangiogenic molecules on DED. These studies will assist in identifying potentially important therapeutic targets in the ocular surface disease associ-ated with Sjögren’s.

Second-Year Goals:During the first year of his Grant, Dr. Chauhan

obtained interesting data on cellular and molecular fac-tors in the induction of corneal lymphangiogenesis and

Reviewers were highly enthusiastic about Dr. Larsen’s grant proposal and cited her excellent training, the pro-ductive lab environment and her dedication as a young tenure-track Assistant Professor trying to move forward in Sjögren’s.

Scientific AbstractNo diagnostic test currently exists for early stage

disease in Sjögren’s. Several protein targets have been identified that change early in disease development, but the cell types that produce these targets and how they cause disease have not been examined. We propose to identify the cell types that produce SS target proteins in the mouse model and test the hypothesis that changes in protein localization precede development of autoimmu-nity. Finally, we will examine patient tissues to deter-mine if these changes also occur in the human disease as a first step towards the development of a molecular diagnostic test for early stages of SS.

Recent SS animal model studies revealed an epithelial homeostasis defect in gland moisture production that precedes the autoimmune response. Microarray profil-ing of an SS mouse model (C57BL/6.NOD-Aec1Aec2) vs. control mice at an early disease stage showed the rac- GAP chimerin1 to be the most highly upregulated mRNA. We hypothesize that misregulation of Rac-1 activity may be an early event in disease initiation.

To test this, we will use the SS mouse model to validate the mRNA data at the protein level and identify the cell type-specific expression and activation of rac1 and chimerin1. Then we will examine the correlation between rac1 and chimerin1 expression and activation and SS in patients. These results may identify an early diagnostic marker for SS, and the novel multiplexing technology will be used to examine other potential diagnostic targets.

research Grant

Mechanisms in Developing Dry Eye

Sunil Chauhan, DVM, PhD Schepens Eye Research Institute, Boston, Massachusetts

“Mechanism and Functional Relevance of Corneal Lymphangiogenesis in Dry Eye Disease”

Dr. Chauhan was awarded a second-year renewal grant in 2011.

First-Year Grant:Dr. Chauhan hypothesized and provided prelimi-

nary data that immunopathogenesis of dry eye disease (DED) is associated with the selective induction of




facilitation of growth of lymphatic vessels. Dr. Chauhan now will focus on Aim 3 and determine the functional relevance of corneal lymphangiogenesis in the patho-genesis of DED. A manuscript is in preparation for publication on the initial findings.

research Grant

Epigenetics

Lindsey Criswell, MD, MPH, Dsc University of California, San Francisco San Francisco, California

“Epigenetic Profiling of Multiple Cell and Tissue Types in Sjögren’s Syndrome”

Dr. Criswell was awarded a second year in 2011 for her grant project.

First-year Grant:Epigenetic modifications such as DNA methylation

do not affect the genetic sequence; however, they do play a critical role in transcriptional regulation of genes and subsequent gene expression. Methylation of DNA can be detected on a large scale basis using recently devel-oped high-throughput technologies. The identification of unique epigenetic profiles in Sjögren’s will signifi-cantly transform our understanding of disease etiology and may lead to more effective approaches to preven-tion, diagnosis and treatment.

Dr. Criswell proposed to perform a comprehensive screen of 27,578 highly informative CpG sites spanning 14,495 genes across the genome using DNA derived from peripheral blood mononuclear cells (PBMCs), saliva and labial salivary gland biopsy tissue from 30 Sjögren’s cases and 30 controls to identify epigenetic profiles associated with disease susceptibility (Aim 1). We also proposed the collection of fresh blood samples to perform epigen-etic studies in specific cell types following utilization of sophisticated cell sorting techniques (Aim 2).

Dr. Criswell participated in the panel on genetics during the SSF annual program during ACR in 2010.

Second-year Goals:Dr. Criswell’s group determined the minimum vol-

ume of saliva needed for DNA extraction, established the cell sorting protocol for the project and tested the viability of the proposed process for storing blood sam-ples. During the second year of her grant, Dr. Criswell will collect the fresh blood samples from SS cases and controls. She also added a new goal of pursuing CD19+ B cells and CD4+ T cells as well as CD14+ monocytes (as described in the original proposal).

Dr. Criswell spoke on her progress in epigenetic pro-filing during the International Symposium on Sjögren’s Syndrome in Athens in October 2011.

research Grant

Genetics

Kathy L. Moser, PhD Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma

“The Genetic Basis of Human Sjögren’s Syndrome”

Dr. Moser was awarded a second year grant in 2011.

First-year Grant:During the first year of her grant, Dr. Moser focused

on increasing her group’s statistical power to identify genetic effects through additional genotyping of cases in the OMRF genome wide association study (GWAS). In addition to the controls that were genotyped, her analyses included “out of study” control data obtained from collaborators and from the NIH dbGAP resource for a total of 1,754. This GWAS dataset of 424 cases and 1,754 controls has undergone extensive quality control procedures and been analyzed for genetic associations.

Evaluations to determine which candidate associa-tions identified in GWAS could be replicated were carried out using additional independent datasets, and a large number of SNPs previously associated with other autoimmune diseases were assessed. Dr. Moser’s group also performed fine mapping for several loci. For her replication studies, she has genotyped over 192,000 markers in over 1000 cases and over 1600 controls, all independent of the subjects included in the GWAS.

Presentations:Lessard CJ and Moser KL. Recent advances towards understanding the

genetic basis of Sjögren’s syndrome. International Conference on the Tear Film and Ocular Surface, Florence, Italy, 2010.

Moser KL. Panel on genetics during the SSF annual program during ACR in 2010.

Lessard CJ and Moser KL. The Genetic Dissection of the Autoimmune Diseases Systemic Lupus Erythematosus and Sjögren’s Syndrome. Pre-sented: Center for Autoimmune Diseases Research (CREA), Universi-dad Del Rosario, Bogotá, Colombia, 2011.

Lessard CJ and Moser KL. What’s Next after Candidate Gene and Genome-wide Association studies in Autoimmunity? 2nd Colombian Sympo-sium on Autoimmunity, Bogotá, Colombia 2011.

Abstracts:Lessard CJ, Adrianto I, Kaufman K, Jonsson R, Illei G, Rischmueller M,

Nordmark G, Mariette X, Miceli-Richard C, Wahren-Herlenius M, Witte T, Brennan M, Omdal R, Ng F, Rhodus N, Segal B, Scofield RH, Rybicki B for ACCESS, Montgomery CG, Anaya J-M, Harley JB, Moser KL. A high-density genome-wide association study by the Sjögren’s Genetics Network (SGENE) identifies both novel susceptibility loci for primary Sjögren’s syndrome and overlapping effects with other autoimmune disorders. Arthritis Rheum 62(10): S1579, 2010.

Second-year Goals:Dr. Moser’s work over the second year will include ad-

ditional genotyping to further expand her group’s sample sizes. This should further increase the significance levels

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of true associations so they surpass genome-wide thresh-olds. She also will be performing additional analyses of existing data to explore genetic associations with clinical subphenotypes and integrate gene expression data with the genetic data collected through this project. Overall, these studies represent the largest genetic studies per-formed to date in SS and will firmly establish robust associations within the HLA region, IRF5 and BLK and provide a wealth of new candidate loci which warrant further study.

Two articles have been submitted for publication during the second year of the grant. Three presentations and one abstract already have been made by Dr. Moser and her group during the October 2011 International Symposium on Sjögren’s Syndrome in Athens, and the group also will present during the November 2011 American College of Rheumatology meeting.

research Grant

Immunology, Lymphocytic Infiltration and Gene Therapy

Cuong Nguyen, PhD University of Florida, Gainesville, Gainesville, Florida

“Suppression of TH17 cells using IL-27 gene therapy: A potential therapeutic approach for the treatment of Sjögren’s syndrome patients”

Supported by the Galewood FoundationDr. Nguyen’s grant was renewed for a second year in 2011.

First-year Grant:In the first year of his grant, Dr. Nguyen proposed

addressing the question of whether TH17 cells are responsible for glandular destruction; characterizing the different cell populations within lymphocytic foci (LF) of Sjögren’s patients; and examining the efficacy of gene therapy to down-regulate CD4+TH17 cell activity and possibly disease in salivary glands of a murine SS model using an IL-27-expressing rAAV2-viral vector.

Studies on the characterization of IL-17-producing CD4+TH17 cells and those relating IL-22 to disease parameters in human SS patients are completed and published. Dr. Nguyen authored numerous publica-tions and abstracts during the first year of his grant:

Publications: Nguyen CQ, Yin H, Peck AB, Chiorini JA. IL-17: Potential therapeutic

target in Sjögren’s Syndrome using adenovirus-mediated gene transfer. Lab Invest. 2011 Jan;91(1):54-62.

Nguyen CQ and Peck AB. Inflammation in dry eye diseases culminating in loss of ocular homeostasis. Exp Rev Ophthalmology 5:663-679, 2010.

Nguyen CQ, Yin H, Lee BH, Carcamo WC, Chiorini JA, Peck AB. Pathogen-ic effect of IL-17 in induction of Syndrome-like disease using adenovi-rus-mediated gene transfer. Arthritis Res Ther. 2010 Dec 23;12(6):R220.

Tegan N. Lavoie, ByungHa Lee, Cuong Q. Nguyen. Current Concepts: Mouse Models of Sjögren’s Syndrome (invited review). J Biomed Bio-technol. 2011;2011:549107.

Daniel Perry, Ammon B. Peck, Wendy C. Carcamo, Laurence Morel, Cuong Q. Nguyen. The new frontiers of TH17 cells in systemic lupus erythema-tosus. Arthritis. Volume 2011 (2011), Article ID 810649.

Nicolas Delaleu, Cuong Q. Nguyen, Ammon B. Peck, Roland Jonsson. Sjögren’s syndrome: studying the disease in mice. Arthritis Res Ther. 2011, 13:21.

Ammon B. Peck, Cuong Q. Nguyen, Ashok Sharma, Richard A. McIndoe, Jin-Xiong She. The interferon-signature of Sjögren’s syndrome: What does it say about the etiopathology of autoimmunity. J Clin Rheum & Musculoskeletal Med. 2011; 2: 1-17.

Ammon B. Peck, Benjamin T. Saylor, Ashok Sharma, Linh Nguyen, Jin-Xiong She, Richard A. McIndoe, Cuong Q. Nguyen. Differential gene expression profiles during early phase Sjögren’s syndrome in C57BL/6.NOD-Aec1Aec2 mice identifies focal adhesion maturation preceding development of autoimmunity in the lacrimal glands. Invest Ophthalmol Vis Sci. 2011 Jun 10.

Tegan N. Lavoie, Carol M. Stewart, Kathleen M. Berg, Yi Li, Cuong Q. Nguyen. Expression of interleukin-22 in Sjögren’s Syndrome: Signifi-cant correlation with disease parameters. Scand J Immunol. 2011 Jun 6. doi: 10.1111/j.1365-3083.2011.02583.x.

Abstracts:Delaleu Nicolas, Nguyen Cuong Q., Jonsson Roland, Peck Ammon B. Using

systems biology and network analyses to define the altered salivary gland tissue homeostasis prior to the onset of Sjögren’s syndrome. World Im-mune Regulation Meeting-V: Innate and Adaptive Immune Responses & Role of Tissues in Immune Regulation. Davos, Switzerland 24-27 March 2011.

Lee BH, Nguyen CQ, Peck AB. Defective IL-27 signaling: a possible underlying cause of the sexual dimorphism in autoimmune-mediated Sjögren’s syndrome. Keystone Symposia: Immunoregulatory Networks. Beaver Run Resort, Breckenridge, Colorado. April 1 - April 6, 2011.

Hongen Yin, Cuong Nguyen, Yuval Samani, Toshimitsu Uede, Ammon Peck and John Chiorini. Prevention of murine sjögren’s syndrome by local delivery of adeno-associated virus mediated cytotoxic T-Lymphocyte antigen 4- immunoglobulin G fusion protein. Immunology 2011, 98th Annual Meeting. The American Association of Immunologists. San Francisco CA May 13-17, 2011.



Risk Factors: Multiple associated factors have been identified, including Sjögren’s, anterior blepharitis, contact lens wear, Demodex mites, androgen deficiency, menopause, aging, higher cholesterol levels, psoriasis, atopy, rosacea, hypertension and benign prostatic hy-perplasia (BPH). In addition, medications used to treat BPH, antiandrogens, postmenopausal hormone therapy (e.g., estrogens and progestins), antihistamines, antide-pressants and retinoids have also been identified.

So is MGD dry eye?This question was one of the more controversial

discussion topics across all subcommittees (see the Introduction to the Report). In the end, while most believe MGD contributes significantly to evaporative dry eye, the largest subcategory of dry eye disease, the question remains unanswered. I believe that not a day goes by in clinical eye care in which a patient with MGD is not sitting in every office. It may be a patient awaiting cataract surgery, a symptomatic contact lens wearer, a postmenopausal woman, a patient on glaucoma medi-cations or the student on accutane therapy—or the family member of the previously described patient. It is our choice how to diagnose and manage these patients, our job to sort through their ocular surface disease. Continued clinical experience will provide the impetus to design studies to answer that critical question.

references1. Nichols KK. The International Workshop on Meibomian Gland Dysfunc-

tion: Introduction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1917-21.

2. Nichols KK, Foulks GN, Bron AJ, et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1922-9.

3. Nelson JD, Shimazaki J, Benitez-del-Castillo J, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Definition and Classification Subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7.

4. Tomlinson A, Bron A, Korb D, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Diagnosis Subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 2006-49.

5. Schaumberg D, Nichols J, Papas E, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommitee on the Epi-demiology of, and Associated Risk Factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 1994-2005.

6. Geerling G, Tauber J, Baudouin C, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dsyfunction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 2050-64.

7. Knop E, Knop N, Millar T, et al. The International Workshop on Mei-bomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology and Pathophysiology of the Meibomian Gland. Invest Oph-thalmol Vis Sci. 2011 Mar 30;52(4):1938-78.

8. Green-Church K, Butovich I, Willcox M, et al. The International Workshop on Meibomian Gland Dysfunction: Report on the Subcom-mittee on Tear Film Lipids and Lipid-Protein Interactions in Health and Disease. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 1979-93.

Editor’s Note: Dr. Nichols is a professor at the University of Houston College of Optometry. She lectures and writes on ocular surface disease and currently chairs the International Meibo-mian Gland Workshop sponsored by the Tear Film and Ocular Surface Society. She is a paid consultant to Allergan, Alcon, Celtic, Eleven Biotherapeutics, Ista, SARcore Biotherapeutics, TearLab, and Pfizer, and has NIH funding to study dry eye in postmenopausal women.


Can we similarly develop an inexpensive drug to reverse Sjögren’s syndrome? The existing evidence sug-gests that the answer is “yes.”

The rationale for using BCG in type 1 diabetes is that the drug temporarily boosts the body’s own produc-tion of tumor necrosis factor, or TNF, a molecule that is involved in the inflammatory process. We have shown in mice and humans that the autoreactive cells—that is, the cells responsible for the attack on the body’s healthy organs in people with autoimmune diseases—have a cellular defect that appears to make them uniquely susceptible to death in the presence of elevated TNF (Hayashi and Faustman, Mol Cell Biol. 1999; Ban et al. Proc Natl Acad Sci USA. 2008). This defect is a dys-regulation in NFkB—specifically, a lack of the LMP2 protein—which has also been identified in humans with Sjögren’s syndrome. In fact, a group from Germany has shown that expression of the LMP2 protein is lacking in 100% of people with primary Sjögren’s syndrome (Krause et al. Ann Rheum Dis. 2006).

Moving beyond this rationale, promising preclini-cal evidence also supports moving BCG forward as a potential treatment for Sjögren’s syndrome. Using an approach developed by our lab to successfully reverse advanced type 1 diabetes in mice (Ryu et al. J Clin Oncol. 2001; Kodama et al. Science. 2003)—part of which is the basis for the current clinical trials testing BCG in human type 1 diabetes—Tran et al. observed the regeneration of the salivary glands and pancreas in NOD mice, which exhibit both type 1 diabetes and Sjögren’s-like disease (Ann Rheum Dis. 2007). In my own lab, in tissue culture studies we have seen that elevating TNF can specifically eliminate the autoimmune cells found in the blood of patients with autoimmune diseases, including Sjögren’s syndrome (Ban et al. Proc Natl Acad Sci USA. 2008).

This evidence, taken together with the recent success of BCG in the Phase I diabetes trial, makes Sjögren’s syndrome an excellent candidate for clinical trials testing BCG. As with the human type 1 diabetes trials, this next set of clinical studies will likely rely on phil-anthropic dollars, since the testing and development of a generic drug lacks the financial incentives that are often required to gain the interest of pharmaceutical companies. Despite this challenge, the success of BCG vaccination in early human clinical trials paves the way for human trials in Sjögren’s syndrome—all using a low-cost drug that, if successful, would be affordable for patients everywhere and aimed at restoring salivary and eye gland secretions.

“Diabetes Research” Continued from page 1 t


Oral HealtH aND eDuCatION NeWS


Lawsuit Challenges Medicare Reimbursement for Dental Treatment in Sjögren’s

Sjögren’s patients often face extensive dental treatment, and, tradi-tionally, Medicare has not covered these costs. A lawsuit pending in U.S. federal court challenges this. While the original suit, Fournier v. Leavitt, was filed in 2008, it was recently amended by the Center for Medicare Advocacy in the U.S. District Court for the District of Arizona to include three Medicare patient plaintiffs, one of whom has Sjögren’s.

Medicare will cover dental work if the oral problems were caused by medical conditions specifically listed under their coverage. However, cov-

erage is not available for loss of salivary gland function due to Sjögren’s or radiation treatment for head and neck cancer, for example. The lawsuit states:

Issue: Whether the Secretary’s exclusion of coverage for dental care in extraordinary circum-stances where the care is necessary to treat a medical condition violates the Medicare statute and policy provisions, and the Equal Protection Clause.

Relief Sought: Declaratory judgment that the policy is invalid, and a preliminary and perma-nent injunction against the application of the policy to an individual beneficiary.

It was updated July 20, 2011.For more information, visit the Center for Medicare Advocacy website at

www.medicareadvocacy.org.

Awareness Initiative Launched for Dry Mouth Due to MedicationsFour leading dental and pharmacy organizations are partnering on an initiative to increase

awareness of the impact of medications on xerostomia. The American Dental Association, Academy of General Dentistry, American Academy of Periodontology and the American Phar-macists Association have teamed up to ensure the public knows that dry mouth is a common side effect of more than 500 medications and can lead to major oral health problems. Because Sjögren’s causes xerostomia, the addition of such a medication can exacerbate the dryness patients already experience, and clinicians need to be aware of medications that can increase dryness in their Sjögren’s patients.

CODA Will Set Accreditation Standards for Dental Therapy Education Programs

The Commission on Dental Accreditation (CODA) has agreed to establish accreditation standards for dental therapy education programs. The decision came in response to a request from the University of Minnesota School of Dentistry that accreditation standards be set. CODA will appoint a Task Force to develop standards, a process that is expected to take at least two years. The Task Force will report on its progress to the full Commission in August 2012 and will accept comments from communities of interest throughout the process.

CODA’s mission is to “serve the public by establishing, maintaining and applying standards that ensure the quality and continuous improvement of dental and dental-related education and reflect the evolving practice of dentistry. Visit www.ada.org/117 for more information.

Cuong Q. Nguyen, Adebola O. Ogunniyi and Christopher J. Love. Charac-terization of B cell repertoires in Sjögren’s syndrome by microengraving. Immunology 2011, 98th Annual Meeting. The American Association of Immunologists. San Francisco CA May 13-17, 2011.

Cuong Q. Nguyen and Adebola O. Ogunniyi. Single cell analysis revealed autoimmune B cell repertoires in Sjögren’s syndrome. Cold Spring Har-bor Laboratory. Workshop on Single Cell Analysis Cold Spring Harbor, NY, July 22 - 24, 2011.

Second-year Goals:During the second year of his research grant, Dr.

Nguyen will continue to solicit human SS biospecimens to further his research into the cell populations within LF and their pathogenic role in SS as well as explore the capability of suppressing SS disease progression utilizing gene therapy. Dr. Nguyen is investigating his hypotheses that exogenous IL-27 can inhibit the differentiation and proliferation of CD4+ TH17 cells from SS patients and, second, that gene therapy treatment with an IL-27-expressing rAAV2 viral vector can prevent, and possibly reverse, development and onset of SS in his lab’s animal

“Research Grants” Continued from page 11 t model of primary SS. To complement data from the group’s in vitro studies, he has initiated studies to see if IL-27 can suppress TH17 cell activity in-vivo. It is now anticipated that the results of this pilot study will lead to a follow-up study to investigate further the role of IL-27 at the molecular level.

Two publications, including an additional manuscript focusing primarily on the biological and immunological roles of IL-22 and another showing gender-dependent activity for IL-27 in regulating IL-17, are in progress and will be noted in the Quarterly upon publication.

The SSF thanks its Research Review Committee for its leader-ship in directing the SSF Research Program: Chair, Denise Faustman, MD, PhD; Elaine Alexander, MD, PhD; Philip C. Fox, DDS; and Austin Mircheff, PhD. Additional reviewers for Student Fellowships and Outstanding Abstract Awards who give of their time and expertise include: Steven E. Carsons, MD; Nancy Carteron, MD; Philip L. Cohen, MD; Michael A. Lemp, MD; Vidya Sankar, DMD, MHS; Daniel J. Wallace, MD. n

NEW, NEW, NEW!The Sjögren’s Book – Fourth Edition Edited by Daniel J. Wallace, MD

The NEW 2011 Edition of the Sjögren’s handbook has been completely revised and expanded with All NEW chapters and the latest information on Sjögren’s!

This book can be purchased online at www.sjogrens.org/ssfstore or by contacting the Sjögren’s Syndrome Foundation office at 800-475-6473.

For more information on Sjögren’s syndrome contact the Sjögren’s Syndrome Foundation at: 6707 Democracy Blvd, Suite 325, Bethesda, MD 20817 • 800-475-6473 • www.sjogrens.org • [email protected].

Patient Education SheetMuscle and Joint Pain in Sjögren’s

The SSF thanks Alan Baer, MD for authoring this Patient Education Sheet. Dr. Baer is an Associate Professor of Medicine, Director, Jerome L. Green

Sjogren’s Center, Johns Hopkins University School of Medicine.

Clinicians: Please make multiple copies of this Patient Education Sheet and distribute to your patients.

Joint and muscle pain in Sjogren’s syndrome may result from a variety of causes including inflammation, fibromyalgia, age-related osteoarthritis, vitamin D deficiency, hypothyroidism etc. Work with your rheumatologist to identify the specific cause(s) of your pain and find the best treatment regimen for you. Maintain a positive attitude and be an active partner in the management of your pain. The tips below will also help.

Become knowledgeable about your medications.

Get a good night’s sleep.• Maintain a regular sleep schedule.

• Set aside an hour before bedtime for relaxation. Listen to soothing music. Consider taking a warm bath before going to bed.

• Make your bedroom as quiet and comfortable as possible.

• Avoid caffeine and alcohol late in the day.

• Avoid long naps during the day.

Exercise regularly with the goals of improving your overall fitness and keeping your joints moving, the muscles around your joints strong and your bones strong and healthy.

• A physical therapist, occupational therapist, or your health-care provider can prescribe an exercise regimen appropriate for your joint or muscle problem.

• Start with a few exercises and slowly add more.

• Make your exercise program enjoyable. Do it with your spouse or a friend. Include recreational activities, such as dancing, walking, and miniature golf.

• Try different forms of exercise, such as Tai chi, yoga and water aerobics.

Balance rest and activity.• Pace yourself during the day, alternating heavy and light activities

and taking short breaks to rest.

Control your weight.

Protect your joints and muscles.• Use proper methods for bending, lifting, and reaching.

• Use assistive devices, such as jar openers, reach extenders and kitchen and garden tools with large rubber grips that put less stress on affected joints.

Use various therapeutic modalities that can relieve joint and muscle pain.• Use heat (heating pads, warm shower or bath, paraffin wax) to relax your muscles

and relieve joint stiffness.

• Use cold packs to numb sore joints and muscles and reduce inflammation and swelling of a joint

• Consider massage therapy.

• Practice relaxation techniques, such as guided imagery, prayer, and self-hypnosis.

Sjögren’s QuarterlySjögren’s Syndrome Foundation Inc.6707 Democracy Blvd., Ste 325

Bethesda, MD 20817

New Product for Dry Mouth and Sjögren’s

A new dry mouth product is available for your Sjögren’s patients! Aquoral™ Artificial Saliva is a prescription spray indicated for xerostomia. Up to 70% of those using the product in clinical trials demonstrated positive results in their mouth dryness, burning sensation, viscous saliva and cracked lips. In addition, patients exhibited improved chewing, swallowing, speaking and taste. No adverse effects were reported. Aquoral™ comes in a 40 ml (1.4 fl oz) pump spray canister. Patients are advised to spray the mouth 3-4 times a day, two sprays per dose. It is covered under most health care plans. For more information, visit www.aquoral.com.

JOIN THE SSF AT ACR!SSF EXHIBIT BOOTH - #235Hall F1, McCormick Place, West

Sunday, November 6, 2011, 10:00 AM - 5:00 PMMonday, November 7, 2011, 10:00 AM - 7:00 PMTuesday, November 8, 2011, 10:00 AM - 5:00 PM

Visit us at the SSF Booth to obtain a copy of The Sjögren’s Book, 4th Edition! We will also have the latest information on Sjögren’s events, copies of our educational materials and information on our

research program. We are on a corner at Booth #235.

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