Relationship Between Cyclic Citrullinated Peptide Antibodies Positivity and HLA-DRB1 Shared Epitope Alleles in Patients with Rheumatoid Arthritis in Turkey

Abstract

ÖzetAmaç: HLA DRB1 ortak epitop alelleri romatoid artritin (RA) en belirgin genetik risk faktörü olup, sınıf 2 HLA molekülünün peptid sunan bölümünde bir amino asit dizilimi tarafından kodlanmaktadır Son zamanlarda bu ortak epitop alellerinin RA'lı hastalarda sitrüllenmiş proteinlere karşı antikorların gelişimi için bir risk faktörü olabileceği öne sürülmektedir. Bu çalışmada Türk toplumundaki RA'lı hastalarda siklik sitrüline peptid antikorları (anti-CCP) pozitifliğinin HLA-DRB1 allellerinin taşıdığı ortak epitopla olan ilişkisi araştırılmıştır. Gereç ve Yöntem: Çalışmaya kliniğimizde yeni tanı konulmuş ya da tedavi altında olan 60 RA'lı hasta dahil edildi. Kontrol grubunu ise 60 sağlıklı gönüllü oluşturdu. RA'lı hastalarda anti-CCP düzeyleri enzim-bağımlı immunosorbent ölçüm metoduyla, HLA-DRB1 tiplemeleri ve OE ölçümü polimeraz zincir reaksiyonu yöntemi ile araş-tırıldı. Sağlıklı gönüllülerde ise sadece anti-CCP düzeyleri ölçüldü. Bulgular: Romatoid artritli hastalarda OE pozitifliği %50 olarak saptandı ve bu hastaların %30'u çift kopya OE taşıyordu. Anti-CCP pozitifliği RA'lı hastalarda %73.3 iken, kontrol grubunda bu oran %0 olarak saptandı. OE varlığının anti-CCP pozitifliğini arttırdığı (OR=4. Abstract Objective: The most characteristic genetic risk factors for rheumatoid arthritis (RA), the HLA-DRB1 shared epitope (SE) alleles, encode for a common amino acid sequence in the peptide-presenting part of the HLA class II molecule. These SE alleles have been described recently to be a risk factor for the development of antibodies against citrullinated proteins in RA. The current study was performed to investigate the association between the cyclic citrullinated peptide antibodies (anti-CCP) and HLA-DR1 HLA-DRB1 shared epitope alleles in patients with RA in Turkey. Materials and Methods: Sixty patients with RA who were newly diagnosed or under conventional treatment in our clinic and 60 healthy volunteers as controls were enrolled in the study. In patients with RA anti-CCP levels were investigated with enzymelinked immunosorbent assay and HLA-DRB1 subtyping and SE was assessed by polymerase chain reaction. Only anti-CCP was measured in healthy volunteers. Results: SE was positive in 50% of the patients with RA. Amongst the SE carriers, 30% of them were carrying double copy of SE. While anti-CCP was positive in 73,3% of patients with RA, this ratio was 0% in healthy volunteers. We determined that the existence of SE increases the positivity of anti-CCP (OR=4,3, 95% [CI], P=0.04 ), and a significant relationship was found between the anti-CCP positivity and the RF positivity. (OR=5,3, 95% [CI] P<0.05). Conclusion:The results of the present study revealed that Turkish patients with RA carrying SE with HLA-DRB1 genes is significantly related with the production of anti-CCP. The diagnostic sensitivity and specificity of anti-CCP for RA is determined as 73,3% and 100% respectively. (Turk J Rheumatol 2010; 25: 12-8)

Association of Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotypes with Rheumatoid Arthritis in Sudanese patients

“…Nevertheless, compared to anti-CCP, our data showed no significant association was found between HLA genotypes and RF. This finding is similar to the studies conducted in Turkish and Saudi populations, where the association was found with positive anti-CCP and not with RF ( 43 , 44 ). This is not surprising as anti-CCP is more specific than RF, and seemed to play a pivotal role in the pathogenesis of RA.…”

Association of anti‐cyclic citrullinated peptide antibodies and rheumatoid factor isotypes with HLA‐DRB1 shared epitope alleles in Egyptian rheumatoid arthritis patients

“…On the other hand, recent studies among south Indian populations, and among Bangladeshi RA patients, no significant difference in frequency of anti‐CCP and RF between HLA‐DRB1‐SE‐positive and negative RA patients was found 12,22 . Among Turkish and Saudi RA patients the association was found with positive anti‐CCP and not with RF 23,24 …”