HLA-DRB1 alleles encoding the “shared epitope” are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the β-chain are protective in Mexican mestizos

Ruiz-Morales, Jorge A.; Vargas‐Alarcón, Gilberto; Flores-Villanueva, Pedro O.; Villarreal‐Garza, Cynthia; Hernández-Pacheco, Guadalupe; Yamamoto-Furusho, Jesús K.; Rodrı́guez-Pérez, José Manuel; Pérez-Hernández, Nonanzit; Rull, Marina; Cardiel, M H; Granados, Julio

doi:10.1016/j.humimm.2003.12.009

Cited by 42 publications

(37 citation statements)

References 27 publications

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“…It is important to notice that in this study we only considered HLA-DR4 alleles since other alleles such as DR1, DR14 and DR10 that also present SE were not analyzed. In a previous work, we reported an increased frequency of HLA-DR alleles with the SE in Mexican patients with RA [25]. The association studies indicate that HLA-DR locus accounts for only one third of the overall genetic contribution in RA.…”

Section: Discussionmentioning

confidence: 69%

Tumor necrosis factor-alpha −308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans

Carreón

Zúñiga

Hernández-Pacheco

et al. 2005

Journal of Autoimmunity

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Section: Discussionmentioning

confidence: 69%

Tumor necrosis factor-alpha −308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans

Carreón

Zúñiga

Hernández-Pacheco

et al. 2005

Journal of Autoimmunity

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“…To illustrate, SE was found in 59% of RA patients in Germany, double copy SE was detected in 17.5% of these patients and HLA-DR4 was the most frequent share epitope producing gene with a ratio of 35% (16). In Mexican population, frequency of SE was found as 64,3% in RA patients and the most frequent SE coding gene was found as HLA-DR4 (17). On the other hand, dissimilar to the results obtained in other populations, in a study of Ioannidis et al (18) from our neighbor country, Greece, HLD-DR1 gene was found to be more frequent than DR4 and frequency of SE was 44% in RA patients.…”

Section: Discussionmentioning

confidence: 92%

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

Dayan¹,

Tıkız

Taneli

et al. 2010

Turk J Rheumatol

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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)

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“…The existence of protective alleles has been explored in several autoimmune diseases including type 1 diabetes mellitus [4,[42][43][44], multiple sclerosis [45], lupus nephritis [46], and rheumatoid arthritis [47][48][49][50][51][52]. In PV, multiple studies have reported alleles present at significantly lower frequencies, but there has been no direct demonstration that these sequences downgrade risk.…”

Section: Discussionmentioning

confidence: 99%

Disease Relevant HLA Class II Alleles Isolated by Genotypic, Haplotypic, and Sequence Analysis in North American Caucasians With Pemphigus Vulgaris

et al. 2006

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HLA-DRB1 alleles encoding the “shared epitope” are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the β-chain are protective in Mexican mestizos

Cited by 42 publications

References 27 publications

Tumor necrosis factor-alpha −308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans

Tumor necrosis factor-alpha −308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans

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

Disease Relevant HLA Class II Alleles Isolated by Genotypic, Haplotypic, and Sequence Analysis in North American Caucasians With Pemphigus Vulgaris

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