SYSTEMIC LEVELS OF CERULOPLASMIN OXIDASE

ACTIVITY IN ALLERGIC ASTHMA AND ALLERGIC RHINOCONJONCTIVITIS

Arzu Didem YALÇIN.MD

Internal Medicine, Allergy and Clinical Immunology

• In our previous study, we reported that omalizumab treatment was clinically effective in severe persistent asthma patients with co-morbid allergic conditions . Omalizumab blocks binding of free IgE on basophils and mast cells, thus inhibiting their activation by allergens. Omalizumab treatment significantly reduced the nasal symptom score, latex allergy symptom, venom allergy symptom, food allergy symptom, urticaria and angioedema across all patients studied

• Yalcin AD, Bisgin A, Çetinkaya R, Gümüslü S. Clinical efficacy of omalizumab in severe persistent asthma and co-morbid conditions. Congress of the European Academy of Allergy and Clinical Immunology. P:946, ,2011.DOI: 10.3252/pso.eu.30eaaci.2011

• Yalcin AD. Clinical Course and Side Effects of Anti IgE monoclonal antibody in Patients with Severe Persistent Asthma . Respirology. 2011. Clinical Lab.2012.

• Our earlier studies provided a novel perspective on severe persistent allergic asthma and the effect of omalizumab treatment, using serum soluble TNF-related apoptosis-inducing ligand, total antioxidant capacity, hydrogen peroxide, malondialdehyde as markers and total nitric oxide concentrations measurements

• Yalcin AD, Gorczynski RM ,Parlak GE, Kargi A, Bisgin A, Şahin E, Kose S, Gumuslu S. Total antioxidant capacity, hydrogen peroxide, malondialdehyde and total nitric oxide concentrations in patients with severe persistent allergic asthma: its relation to omalizumab treatment. Clin. Lab. 2012;58(1-2):89-96.

• Yalcin AD, Bisgin A, Kargi A, Gorczynski RM. Serum soluble TRAIL levels in patients with severe persistent allergic asthma: its relation to Omalizumab treatment. Med Sci Monit 2012; 18(3): PI 11 – 15.

Background

The role of ceruloplasmin oxidase (COA)involving the interaction of oxidant and antioxidant balance in allergic diseases is still unknown.

Objective: Our study was designed to examine the changes in COAs in severe persistent asthma, new diagnosed allergic asthma and allergic rhinitis patients

Material and Methods

• The study included 20 healthy individuals as control group(group-I) and 50 patients whom divided into two groups; Group II was including 15 new diagnosed allergic asthma patients, group III was including 15 patients with severe asthma and in the fourth group there were 20 patients with allergic rhinitis. Group III was studied in two different times, severe asthma patients who were pre-(group III-A) and post-treated(group III-B) with omalizumab. Group IV was also studied in two different times, pre-(group IV-A) and post-treatment(group IV-B) with specific immunotherapy modalities. All the post-treatment measurements were 12 months after the therapy. All the patients were assessed by the albumin level, hs-CRP and COA.

Material and Methods

• Ceruloplasmin (CP) is a copper-containing alpha-2-glycoprotein with a molecularweight of approximately 132 kDa. CP has diverse functions. It is essential for iron homeostasis, is involved in angiogenesis and under different conditions can act as either a pro-or an anti-oxidant

• Serum ceruloplasmin oxidase activity (COA) was measured according to the methods of Schosinky et al. Gumuslu et al. and Gocmen et al. using o-dianisidine dihydrochloride as a substrate. COA was estimated in IU/L, using molar extinction coefficient (ε) (ε =96×104 L/(mol × cm), in terms of substrate consumed.

Albumine (g/dL) , Hs-CRP (mg/L) , Ceruloplasmin oxidase activities (IU/L) incontrol (healthy individuals) and patient groups (group II, IIIA, IIIB, IVA, IVB).

Groups n Albumine Hs- CRP(mg/L)

COA(IU/L)

control 20 3.19 ± 0.38 1.05± 0.13 38.33 ± 0.56Group II (newdiagnosed allergicasthma patients)

15 3.20 ± 0.25 1.26± 0.18 48.97 ± 0.42

Group III-A (severepersistent asthma preomalizumab)

15 3.19 ± 0.42 3.50± 0.21 58.75 ± 0.91

IIIB 15 3.20 ± 0.56 2.66± 0.23 52.81 ± 0.47

Group IV-A (allergicrhinoconjunctivitispre-immunotherapy)

20 3.19 ± 0.67 1.12± 0.17 40.07 ± 0.58

IVB 20 3.32 ± 0.85 1.17± 0.15 32.55 ±0.36

Serum high-sensitivity C-reactive protein levelsSamples of peripheral venous blood were collected and centrifuged for 10 min at 1,300×g at 4°C. The sera were stored at −20°C. Serum hs-CRP levels were measured using hs-CRP assay (Behring Latex-Enhanced using the Behring Nephelometer BN-100; Behring Diagnostics, Westwood, MA, USA). The sensitivity of the assay ranged 0.04–5.0 mg/L−1.

Serum albumin levels were measured using the bromocresol green dye binding method .

Skin prick tests Commercial extracts used were manufactured by Alyostal ST-IR(Starallergenes S.A.-France).

The difference of the COA between healthy control group and all patient groups except the non-treated allergic rhinoconjunctivitis patients were significant. Also the difference between severe persistent asthma groups and allergic rhinoconjunctivitis groupwere significant. There is a significant difference between group II and groups III-A, IV-A and IV-B; and between pre- and post-treated patients (Figure I).

In addition there is a correlation between hs-CRP and COA in group III-A.

Results

• COA of control and patient groups. The p values were as follows: a) p<0.005, group II vs group I, b) p<0.005, group III-A vs group I, c) p<0.005, group III-A vs group II, d) p<0.005, group III-B vs group I, e) p<0.005, group III-B vs group III-A, f) p<0.005, group IV-A vs group I, g) p<0.005, group IV-A vs group II, h) p: <0.005, group IV-A vs group III-A, i) p: <0.005, group IV-A vs group III-B, j) p: <0.005, group IV-B vs group II, k) p: <0.005, group IV-B vs III-A, l) p: <0.005, group IV-B vs group III-B, m) p: <0.001, group IV-B vs IV-A. Values represent mean ± SEM. Group I: healthy control, group II: new diagnosed allergic asthma patients, group III-A: severe persistent allergic asthma pre-omalizumab, group III-B: severe persistent asthma post-omalizumab, group IV-A: allergic rhinoconjunctivitis pre-immunotherapy, group IV-B: allergic rhinoconjunctivitis post-immunotherapy.

Conclusions

• Our data suggest that hs-CRP and COA might be important in revelation of patients with allergy related diseases.

THANK YOU.

• Prof. Dr. Reginald M GORCZYNSKI, MD, Prof. Dr. Reginald M GORCZYNSKI, MD, PhD: PhD: Division of Cellular & Molecular Biology, Toronto Division of Cellular & Molecular Biology, Toronto Hospital, University Health Network, Toronto, ON, Hospital, University Health Network, Toronto, ON, Canada.Canada.

• Gizem Esra PARLAK MScGizem Esra PARLAK MSc: Department of : Department of Biochemistry, Faculty of Medicine, Akdeniz University, Biochemistry, Faculty of Medicine, Akdeniz University, Antalya, Turkey.Antalya, Turkey.

• Prof. Dr. Saadet GUMUSLU, Ph.D.: Prof. Dr. Saadet GUMUSLU, Ph.D.: Department Department of Biochemistry, Faculty of Medicine, Akdeniz University, of Biochemistry, Faculty of Medicine, Akdeniz University, Antalya, Turkey.Antalya, Turkey.

• REYHAN, RAHİME, HALE, BÜLENTREYHAN, RAHİME, HALE, BÜLENT