management autoimmune health extravaganza reactivity...
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Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 1
Aristo Vojdani, PhD
Health Extravaganza 2013
Anaheim, CA
• Develop dietary protocols that promote healthy gut microbiota.
• Assess intestinal permeability to large molecules that activate immune responses.
• Use testing methods for predictive antibodies to identify target tissues of autoimmune reactivity.
• Implement strategies to manage/prevent autoimmune reactivity.
Patient with Multiple Sclerosis, Gluten Ataxia, Gut and Blood‐Brain
Barrier Permeability
Patient with Multiple Sclerosis, Gluten Ataxia, Gut and Blood‐Brain
Barrier Permeability
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A 42 year‐old man5’8” in height weighing 182 lbs. following
a 3‐week history of progressive neck,
back and muscle pain with weakness of
the limbs was referred to a neurologist.
On the day prior to referral, he
developed difficulty in passing urine with
tingling and sensory disturbance in his
trunk and legs to a degree where he was
unable to climb stairs.
A series of immunological profilesand neurological examinations wasinitiated.
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TESTS RESULTS TESTS RESULTS
Chemistry Normal Mycobacteria Negative
Hemoglobin 10.8 g/dl Borrelia Negative
ANA Normal CMV Negative
Rheumatoid factor Normal EBV Negative
Immune complexes Normal Herpes Type 6
Negative
Total Ig Normal HTLV‐1 and ‐2 Negative
Cardiolipidantibodies
Normal Syphilis Negative
Thyroid function Normal CSF protein 0.7 g/L
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Neurological examination revealed reduced
corrected visual acuity of 6/48 in the right eye and
6/36 in the left eye with normal eye movements.
The patient had pyramidal weakness in both legs
with mildly‐based gait. Pinprick examination
demonstrated hemisensory level below D10 on both
sides. An MRI scan of the brain showed mild white
matter abnormalities with mild generalized atrophy,
which has been observed in patients with MS.
However, to exclude the possibility of gluten
sensitivity, anti‐gliadin, transglutaminase, and GAD‐
65 antibody tests were performed.
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 2
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Gliadin tTg‐2 tTg‐6 GAD‐65
IgG, IgM and IgA antibody levels tested against different antigens in patients with multiple sclerosis (MS) expressed as index.
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Additionally, the following tests were also
performed: IgG, IgM and IgA antibody against LPS,
zonulin/occludin, intestinal ZOT receptor, cell junction
protein, MMP‐3, brain ZOT binding protein, brain ZOT
receptor, calprotectin, GFAP, α‐B crystallin, BBB protein,
and MBP. Results are summarized in the following figure.
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IgG, IgM and IgA antibody levels tested against different antigens in patients with multiple sclerosis (MS) expressed as index. They show a significant elevation in antibody levels against MBP and GFAP, confirming the abnormal MRI findings and a diagnosis of MS. Furthermore, a significant elevation of antibodies against zonulin/occludin, calprotectin and BBB protein indicated involvement of the GI tract with enhanced gut and BBB permeability in this patient.
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Taken all together, the results of the neurological examination, highly abnormal zonulin/occludin and calprotectin results, the significant elevations in antibody levels against gliadin, tTg‐6, GAD‐65, MBP, GFAP, and BBB protein support the diagnosis of gluten ataxia.
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Based on these test results, the
patient was put on a gluten‐free diet and
given 1 g intravenous methylprednisolone
for five days with some resultant clinical
improvement. At this point the patient
was put on β‐seron, showing significant
improvement fifteen days later.
Furthermore, 200 mg of minocycline
IV glutathione, plus probiotics glutamine,
N‐acetylcysteine, EPA/DHA, vitamin D,
lactoferrin, xylitol, and boswellic acid
were given for repairing the damaged
BBB and gut barriers. Three months after
this regimen the patient’s overall health
had improved significantly.
Gut Inflammatory Diseases
Food Allergies, Celiac Diseaseand Autoimmunities
Enhanced Gut Permeability
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THE ROOT CAUSE OF AUTOIMMUNITYTHE ROOT CAUSE OF AUTOIMMUNITY
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 3
MUCOSAL IMMUNE ABNORMALITIES
IMBALANCED GUT FLORA
INTESTINAL BARRIER DYSFUNCTION
SYSTEMIC INFLAMMATION
NEUROINFLAMMATION
NEUROINVASION
NEURODEGENERATION
From mucosal immune abnormalities to neuroinflammation and neurodegeneration.13
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THE PROPER ENVIRONMENT FOR PROPER GROWTH
Like all living things, bacteria need the appropriate nurturing environment in order to achieve maximum growth potential. Different kinds of bacteria thrive or fail according to the kinds of nutrients in the media that constitute their environment. 16
A culture medium is a special medium used in microbiological laboratories to grow different kinds of microorganisms. A growth or a culture medium is composed of agar plus different nutrients, such as blood, heart, brain, chocolate, soy, egg, rice, sugar, salt, yeast, etc. that are essential for a microbial growth.
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Examples of differential media
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Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 4
S. aureus onTryptic Soy Agar
C. albicans onRice Agar
S. enteritidis onMacConkey Agar
K. pneumoniae onEosin‐methylene Blue Agar
Legionella onBuffered Charcoal Yeast Extract Agar
Salmonella onTriple Sugar Iron Agar
Xanthomonas onAcidified Potato Dextrose Agar
Examples of culture media
S. typhimurium onHektoen Enteric Agar
Gamma Hemolysis onBlood Agar
H. influenzae onChocolate Agar
S. epidermis onMannitol Salt Agar
Chaetomium onCorn Meal Agar
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• Tight Junction Proteins
• Actomyosin Network
• Gut Bacteria
• Large Molecules
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ALTERNATIVE THERAPIES, 2013, 19(1):12-24)
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The permeability of the epithelium to very small sugar molecules such as lactulose/mannitol—used for the past 50 years to gauge intestinal permeability—does not necessarily correlate with epithelial permeability to macromolecules…the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders.
The permeability of the epithelium to very small sugar molecules such as lactulose/mannitol—used for the past 50 years to gauge intestinal permeability—does not necessarily correlate with epithelial permeability to macromolecules…the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders.
Bacterial Endotoxin(LPS)
IgG, IgM, IgA
ActomyosinNetwork
IgA
Occludin / ZonulinIgG, IgM, IgA
The triggers and mechanisms involved in enhanced (exacerbated) intestinal permeability and how to use the next generation of testing for Intestinal Permeability Identification (IPI).
Permeability/Dysbiosis Epithelial Cell Damage Tight Junction Damage
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LPS
Occludin/
Zonulin
Acto‐
myosin
Clinical Indication Clinical Approach
+ ‐ ‐ Gut flora dysbiosis; low‐grade inflammation; metabolic
disorder
Pre‐ and probiotics
+ + ‐Breakdown in intestinal barrier integrity by bacterial
antigens through paracellular pathway; low‐grade
inflammation; metabolic disorder
Pre‐ and probiotics
Heal the gut
‐ + ‐Breakdown in intestinal barrier integrity by factors other
than bacterial antigens, through paracellular pathway
Reduce stress
Heal the gut
+ ‐ +Breakdown in intestinal barrier integrity by bacterial
antigens through transcellular pathway; low‐grade
inflammation; metabolic disorder
Pre‐ and probiotics
Heal the gut
‐ ‐ +Autoimmunity (such as Celiac Disease) against mucosal
epithelium and other tissue cell cytoskeleton
Anti‐inflammatories.
‐ + +
Breakdown in tight junction integrity by factors other
than bacterial antigens and autoimmunity against
mucosal epithelium.
Reduce stress
Anti‐inflammatories
Heal the gut
+ + +
Breakdown of intestinal barrier integrity through
transcellular and paracellular pathways and gut flora
dysbiosis; low‐grade inflammation; metabolic disorder
Pre‐ and probiotics
Anti‐inflammatories
Heal the gut
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 5
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CASE REPORTS
• 60 y.o. Male• problems with stiffness started in the neck 15 years ago and gradually progressed to the whole body. Accompanied by muscle weakness. Stiff‐person syndrome.
• Severe swelling of hands and knees. Knee swelling is so bad he is unable to exercise. Was an gymnast and active most of his life and this bothers him. Drinking Coors Light causes a rhinorrhea (nasal discharge and congestion).
• X Rays reveal no radiological evidence of arthritis. ESR mildly elevated at 27.
• Current Medical History: Psoriasis (7‐8 Years), Sleep Apnea (using CPAP of 7)
• Environmental History: Used a product called ‘Roundup’ about 15 years ago
• Been evaluated by numerous physicians. Also has had numerous cleanses through the years
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Wheat IgG
Wheat IgA
WGA IgG
WGA IgA
Gli‐33 IgG
Gli‐33 IgA
Gli‐17 IgG
Gli‐17 IgA
Gli‐15 IgG
Gli‐15 IgA
Gli‐17 IgG
Gli‐17 IgA
Glutenin‐21 IgG
Glutenin‐21 IgA
Glute+P
ro IgG
Glute+P
ro IgA
Gliadin‐tTG
IgG
Gliadin‐tTG
IgA
tTG‐2 IgG
tTG‐2 IgA
tTG‐3 IgG
tTG‐3 IgA
tTG 6 IgG
tTG‐6 IgA
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 6
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0.5
1
1.5
2
2.5
Gluten Grains
Cow's M
ilk
Casein
Casomorphin
Milk Butyrophilin
Whey Protein
Chocolate (milk)
Oats
Yeast
Coffee
Sesame
Buckwheat
Sorghum
Millet
Hemp
Amaranth
Quinoa
Tapioca
Teff
Soy
Egg
Corn
Rice
Potato
• Lab Tests:
– IgG antibodies to gluten, gliadin strongly positive
– Also positive for IgG, IgA to dairy
– Initiated GFD and abstinence from all other food sensitivities including dairy
– Also ordered testing for heavy metal toxicity
• 3 Month Follow Up:
– Joint swelling of knees and ankles completely disappeared and now is significantly more active
– Sleep Apnea significantly better because less swelling in throat
– 20% improvement in stiffness
– Minimal improvement in fatigue
• 34 y.o. male
• Clinical Complaints– Changes in health in last 2 years
– Brain fog
– Fatigue
– Daily low‐grade headaches
– Irritability
– Digestive issues
– Inconsistent and occasional bloody stools
– Acne
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 7
• Family History
– Father and Aunt with lupus
– Brother with Celiac
• Gluten‐free diet was implemented
– Symptoms continued
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ActomyosinIgA
0
0.5
1
1.5
2
2.5
Range
Result
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0.5
1
1.5
2
2.5
3
3.5
4
4.5
Wheat IgG
Wheat IgA
WGA IgG
WGA IgA
Gli‐33 IgG
Gli‐33 IgA
Gli‐17 IgG
Gli‐17 IgA
Gli‐15 IgG
Gli‐15 IgA
Gli‐17 IgG
Gli‐17 IgA
Glutenin‐21 IgG
Glutenin‐21 IgA
Gluteom+P
rodyn…
Gluteom+P
rodyn…
Gliadin‐tTG
…
Gliadin‐tTG
…
Transglutaminase…
Transglutaminase…
Transglutaminase…
Transglutaminase…
Transglutaminase…
Transglutaminase…
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 8
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0.5
1
1.5
2
2.5
Gluten Grains
Cow's M
ilk
Casein
Casomorphin
Milk But
Whey Protein
Chocolate (milk)
Oats
Yeast
Coffee
Sesame
Buckwheat
Sorghum
Millet
Hemp
Amaranth
Quinoa
Tapioca
Teff
Soy
Egg
Corn
Rice
Potato
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0
1
2
3
4
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Parietal + ATPase
Intrinsic Factor
ASCA+A
NCA
Tropomyosin
Thyroglobulin
TPO
21 Hydroxylase
Myocardial
Myosin ‐ a
Phospholipid
Platelet Glyco
Ovary or Testis
Fibulin
Collagen
Arthritic Peptide
Osteocyte
Cytochrome P450
Insulin+Islet Cell
GAD65
MBP
Ganglioside
Tubulin
Cereb
ellar
Synapsin
• After treatment with elimination diet and gut healing protocols
– Sleep 3 hours less per night
– Headaches are gone
– No brain fog
– No irritability
– Consistent stools
– Acne cleared
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 9
• 68 y.o. Female
• Clinical Complaints Jan 2011
– Poorly controlled, labile hypertension
– Multiple food allergies
• Medical History– Age 38 life‐‐threatening episode of Toxic Shock Syndrome Received Prolonged ABX therapy.
– Age 40 Diagnosed with Celiac Disease. Had Been following a strict GFD since. Father was also diagnosed with celiac.
– Early forties. • Exercise & allergy induced adult onset asthma• Hashimoto’s Thyroiditis. Managed with Levothyroxine 75mcg.
– Age 45 Uncomplicated Cholecystectomy.– Age 58 worsening peripheral neuropathy–affects walking.– Age 64 had A dissecting aortic rupture. Surgically repaired. Was given 3% survival chance.
• Medications:
– Carvedilol
– Levothyroxine 75mcg qd
– Acyclovir
• Supplements:
– EPA‐‐DHA, CoQ10, Magnesium, Calcium, TMG, Sylimarin, Red Rice Yeast extract, Zyflamend, B12, DHEA, Vit D3, Venaplex, Glutagenics, Probiotics, Chinese Herbal formulas
February 2011
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ActomyosinIgA
0
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Range
Result
February 2011 February 2011
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 10
ARRAY 2 FEB 2011
OCT 2011
AUG 2012
Actomyosin 23.52 28.56 41.36
O/Z IgG 8.3 1.64 7.2
O/Z IgA 0.96 0.99 2.18
O/Z IgM 0.85 2.33 1.57
LPS IgG 7.49 5 2.63
LPS IgA 1.42 1.77 4.48
LPS IgM 0.4 0.4 0.33
ARRAY 4 FEB 2011
OCT 2011
AUG 2012
Cow's Milk +
Casein +
Casomorphin + +
Milk Butyrophil + + +
American Chz + +
Chocolate (milk) +
Sesame + + +
Hemp + + +
Rye + +
Barley + +
Polish Wheat + +
Buckwheat + + +
ARRAY 4 FEB 2011
OCT 2011
AUG 2012
Sorghum + + +
Millet + +
Spelt +
Amaranth + +
Quinoa + + +
Yeast + +
Tapioca + + +
Oats +
Coffee + + +
Corn + + +
Rice + +
Potato + + +
August 2012 positive to: Teff, Soy, Egg
• Other Significant Lab Results (7/10/12):
– Homocysteine 30.9
– CRP 20.14
– Fibrinogen 520
– MCV 101
August 2012
• Infection exacerbated the subclinical Celiac disease resulting in full‐blown CD.
• Despite CD patient, test results show patient not following GFD.
• By August 2012, no gluten reaction detected, however, intestinal antigenic permeability persistent.
• Healing the barrier upon removal of all triggers will take more time.
• Open intestinal barriers are a contributing factor to the multiple autoimmune reactivity.
CASE STUDY
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Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 11
• 39 y.o. Female
• CC: Joint Pains and Fatigue
• Symptoms started with a severe flu. She developed pain in her joints starting bilaterally in joints of the hand, wrists and knees.
• Also had significant fatigue. Worsening as the day went on.
• Three months later diagnosed with Rheumatoid Arthritis and started on Prednisone and Methotrexate.
• PMH: Pollen allergies in spring.
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0.5
1
1.5
2
2.5
3
3.5
4
Gluten Grains
Cow's M
ilk
Casein
Casomorphin
Milk But
Whey Protein
Chocolate (milk)
Oats
Yeast
Coffee
Sesame
Buckwheat
Sorghum
Millet
Hemp
Amaranth
Quinoa
Tapioca
Teff
Soy
Egg
Corn
Rice
Potato
March 2012 March 2012
65
0
1
2
3
4
5
6
7
Parietal + ATPase
Intrinsic Factor
ASCA+A
NCA
Tropomyosin
Thyroglobulin
TPO
21 Hydroxylase
Myocardial
Myosin
Phospholipid
Platelet Glyco
Ovary/Testis
Fibulin
Collagen
Arthritic Peptide
Osteocyte
Cyto P450
Insulin+Islet Cell
GAD65
MBP
Ganglioside
Tubulin
Cereb
ellar
Synapsin
March 2012 July 2012
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 12
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6
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12
ActomyosinIgA
0
1
2
3
4
5
6Range
Result
July 2012
• Other Tests: Achlorhydria on stomach acid testing.
• Treatment Protocol: Elimination of food allergens, PABA, gut healing, omega 3 fatty acids, substitute for stomach acid.
Follow Up:
Was able to taper off prednisone within 3 months. Occasional flare ups with reintroduction of foods. Increasing omega ‐3’s help on these occasions.
Fatigue improved.
Eight years later never had recurrences, doing great, energy is good.
Catch them early.
The correlation of serum S100B, auto-antibodies and DTIchanges support a link between repeated BBBD andfuture risk for cognitive changes.
The correlation of serum S100B, auto-antibodies and DTIchanges support a link between repeated BBBD andfuture risk for cognitive changes.
71 Proposed mechanism for excitotoxicity from leaky BBB 72
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 13
• 25 y.o. Male
• Clinical Complaints
– Repeated sports injuries
– Concussion symptoms
– Balance problems
– Unable to perform in professional sports
• Passed ImPACT test, but not feeling optimal 00.20.40.60.81
1.21.4
Wheat IgG
Wheat IgA
WGA IgG
WGA IgA
Gli‐33 IgG
Gli‐33 IgA
Gli‐17 IgG
Gli‐17 IgA
Gli‐15 IgG
Gli‐15 IgA
Gli‐17 IgG
Gli‐17 IgA
Glutenin‐21…
Glutenin‐21…
Glute+P
ro…
Glute+P
ro…
Gliadin‐tTG
…
Gliadin‐tTG
…
tTG‐2 IgG
tTG‐2 IgA
tTG‐3 IgG
tTG‐3 IgA
tTG‐6 IgG
tTG‐6 IgA
0
1
2
3
4
5
6
Gluten Grains
Cow's M
ilk
Casein
Casomorphin
Milk But
Whey Protein
Chocolate (milk)
Oats
Yeast
Coffee
Sesame
Buckwheat
Sorghum
Millet
Hemp
Amaranth
Quinoa
Tapioca
Teff
Soy
Egg
Corn
Rice
Potato
Detection of LPS, occludin/zonulin, brain, and BBB protein IgG antibodies in a healthy
individual and patient with TBI .
Detection of LPS, occludin/zonulin, brain, and BBB protein IgA antibodies in a healthy
individual and patient with TBI .
Detection of LPS, occludin/zonulin, brain, and BBB protein IgM antibodies in a healthy
individual and patient with TBI .
Case Management of Autoimmune Reactivity
Health Extravaganza2013
Aristo Vojdani, PhD 14
• Dairy‐free diet
• RepairVite Program to heal the gut barrier
• After 3 months returned to professional sports team
TAKE HOME MESSAGE:
• When you remove the right trigger at an early stage, you can return your patients to optimal health and prevent autoimmune reactivity.
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