Increasing evidence suggests that the rs6822844, within KIAA1109/TENR/IL2/IL21 gene cluster on 4q27, is strongly associated with rheumatoid arthritis (RA) in the Caucasian population. The aim of this study is to investigate the possible association between the SNP rs6822844 and susceptibility to RA in the Algerian Maghreb population, and to explore the association with the clinical and immunological features of RA. The polymorphism rs6822844 was genotyped in 323 RA patients and 323 healthy individuals using the TaqMan assay. A strong association of IL2/IL21 with RA susceptibility was detected in the Algerian population [odds ratio (OR) = 2.57 (95% confidence interval (CI) 1.74-3.83), P = 10(-4) ]. Our results revealed that IL2/IL21 predisposed to disease development in both autoantibody positive and negative disease. Meanwhile, the association was stronger in RA patients with anti-cyclic citrullinated peptides (ACPA) positive than those with ACPA negative [OR = 2.30 (95% CI 1.53-3.51), P = 10(-4) and OR = 1.98 (95% CI 1.01-4.22), P = 0.037, respectively]. Moreover, our findings showed a moderate association of the rs6822844 polymorphism with disease activity (P = 0.014). This study indicates for the first time that there is a strong association between IL2/IL21 rs6822844 variant and susceptibility to RA in the Algerian population, and that this association was independent from the autoantibodies status of RA patients.

Background Increasing evidence suggest that single nucleotide polymorphism (SNP) rs6822844, within KIAA1109-TENR-IL2-IL21 gene cluster, is strongly associated with autoimmune diseases in Caucasian population, including rheumatoid arthritis (RA) [1, 2, 3]. Objectives The aim of this study was to investigate possible association between this polymorphism, susceptibility to RA, auto-antibody profile and RA severity in Algerian population. Methods We investigated 289 Algerian patients with RA and 266 healthy subjects, for rs6822844 polymorphism, using Taqman allelic discrimination assays (Applied biosystems 7500). We recorded demographics, clinical, and laboratory data, including evidence of inflammatory activity and presence of autoantibodies (rheumatoid factor (RF) and cyclic citrullinated peptide antibodies (anti-CCP)). Results The allele G of IL-21 gene polymorphism (rs6822844) was associated significantly with susceptibility to RA (odds ratio (OR) =1.33 [95% CI 1.21 to 1.46], p=0.000). No significant association was observed between rs6822844 and ACPA+ or ACPA- RA groups. However, the major G allele frequency was significantly increased in the RF- RA group compared with RF+ RA group (96% vs 92%, OR=0.95 [95% CI 0.91 to 0.99], p =0.039). Concerning RA severity, the minor T allele was associated with (1) disease activity, assessed by HAQ score and DAS-28-CRP, and (2) ACPA serum levels (p =0.027, p =0.031 and p =0.005 respectively). Conclusions Our results indicate that there is a strong relationship between rs6822844, susceptibility and severity of RA in Algerian population. References Amit K. Maiti, Xana Kim-Howard, Parvathi Viswanathan, Laura Guillén, Adriana Rojas- Villarraga, Harshal Deshmukh, Haner Direskeneli, Güher Saruhan-Direskeneli, Carlos Cañas, Gabriel J. Tobόn, Amr H. Sawalha, Alejandra C. Cherñavsky, Juan-Manuel Anaya, Swapan K. Confirmation of an Association Between rs6822844 at the IL2–IL21 Region and Multiple Autoimmune Diseases: Evidence of a General Susceptibility Locus. Arthritis & rheumatism 2010; 62: 323–329. Hollis-Moffatt JE, Chen-Xu M, Topless R, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PB, Nissen M, Smith MD, van Rij A, Jones GT, Stamp LK, Merriman TR. Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance. Arthritis Research & Therapy 2010; 12: R116. Nina A. Daha, Fina A. S. Kurreeman, Rute B. Marques, Gerrie Stoeken-Rijsbergen, Willem Verduijn, Tom W. J. Huizinga, René E. M. Toes. Confirmation of STAT4, IL2/IL21, and CTLA4 Polymorphisms in Rheumatoid Arthritis. Arthritis & rheumatism 2009; 60: 1255–1260. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1950

Background The B-cell lymphocyte kinase (BLK) is a src family protein tyrosine kinase expressed in B-lineage cells. BLK gene polymorphism was reported as a risk factor in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) susceptibility. Objectives To investigate whether the association of BLK gene polymorphism with RA is present in an Algerian population. Methods The BLK (rs13277113) single nucleotide polymorphism was directly genotyped in 223 RA patients and 200 healthy controls by real time -polymerase chain reaction method (TaqMan Assays). The relationships between anti-citrullinated peptide antibody (ACPA) positivity, rheumatoid factor (RF) positivity and BLK genotypes were analyzed statistically. Disease activity score (DAS28) and HAQ score were also assessed. Results Significant associations between RA and controls were observed for AG heterozygote genotype (21% vs 33%, P=0.004, OR=0.53) and recessive model (AA vs. AG+GG, 94% vs 99%, P=0.002, OR=0.08). Allele frequencies did not differ between patients and controls and between antibodies positive (ACPA, RF) and negative RA (P>0.05). No significant difference in genotypes distribution was found after stratification according to parameters of disease activity (DAS 28 and HAQ, P>0.05). Conclusions Our result indicates that polymorphism in BLK gene is associated with susceptibility to RA in Algerian population but not with the severity. References Génin E, Coustet B, Allanore Y, et al. Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis. PLoS One. 2013 Apr 30;8(4) Viatte S, Plant D, Bowes J, et al. Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated peptide antibody negative patients. Ann Rheum Dis. 2012 Dec;71(12) Zhang H, Wang L, Huang Y, et al. Influence of BLK polymorphisms on the risk of rheumatoid arthritis. Mol Biol Rep. 2012 Nov;39(11). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1943

ObjectivesTo determine the prevalence of thyroid antibodies (TA): antibodies against thyroid peroxidase (A-TPO) and thyroglobulin (A-TG) in Algerian patients with Systemic Lupus Erythematosus (SLE) and in a healthy population matched for age and sex and To search a dependency between the presence of TA and thyroid dysfunction.MethodsTransversal study carried in BenAknoun hospital between January 2012 and May 2014 on 54 patients with SLE matched for age and sex to a control group of 88 healthy persons. For all patients collect of demographic data, duration of the disease and submitting to clinical examination. Thyroid hormones, TSH and autoantibodies against TPO, TG, DNA, Sm, SS-A, SS-B were measured.Data analysis: SPSS Software. Significant value for p≤0,05. Using chi2 test to compare %.Results54 patients with SLE were included in this study (51 women, 3 males). Their average age was 40±11.7 years, mean disease duration was 10±7 years. The majority of patients (63%) had moderate activity against 37% with high activity. A-TPO were found respectively in 22.22% and 14.77% of lupus and controls (p=0.258), A-TG were found in 23.1% and 11.36% (p=0,066). We found a moderate but not significant link between the absence of A-TPO and the presence of anti Sm (p=0.06) and a significant link between the presence of A-TG and the presence of anti SSB (p=0.049). Subclinical hypothyroidism was found respectively in 9.25% and 2.27% of cases (p=0.062) and sub-clinical hyperthyroidism in 7.4% and 5.68% of cases (p=0.682).ConclusionsIn this preliminary study, there was no association between the occurrence of SLE and the presence of TA or subclinical and clinical thyroid dysfunction. But we found a statistical significance association between the presence of A-TG and the presence of antibodies against SS-B.ReferencesAutoimmune thyroid disease in systemic lupus erythematosus and sjögren's syndrome. Scofield RH. Clinical Experimental rheumatology. 1996 May-Jun; 14(3):321-30.Thyroid Autoimmune diseases in patients with systemic lupus erythematosus. DPPO Viggiano, AOS Montandon, VS Barbosa, NA Silva. EULAR 2008-Paris 11-14 juin 2008.Association of systemic and thyroid autoimmune diseases. E Biro, Z Szekanecz, L Czirjak, K Danko, E Kiss, NA Szabo, G Zeher, E Bodolay, G Szegedi, G Bako. Clin Rheumatol.2006 Mar;25(2):240-5.Clinical manifestations and outcome of polyarthralgia associated with chronic lymphocytic thyroiditis. Punzi L, Sfriso P, Pianon M, Schiavon F, Ramonda R, Cozzi F, Todesco S. Semin Arthritis Rheum. 2002 Aug; 32(1):51-5.Autoimmune thyroid disease in systemic lupus erythematosus. Pyne D, Isenberg DA Ann Rheum Dis 2002;61:70–2.Thyroid disease in systemic lupus erythematosus and rheumatoid arthritis. Chan ATY, Al-Saffar Z, Bucknall RC. Rheumatology 2001;40:353–4.Disclosure of InterestNone declared