{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T18:00:54Z","timestamp":1783792854698,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HLA"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rheumatoid arthritis (RA) is an inflammatory disease, which affects synovial joints, and is influenced by environmental and genetic factors, in particular the human leucocyte antigen (HLA) system. In our study, we investigated the association of HLA class II DRB1 and DQB1 alleles and DRB1\u2010DQB1 haplotypes with RA susceptibility in Tunisian subjects. Therefore, HLA class II low\u2010resolution genotyping was done in 110 RA patients and 116 controls, with a<jats:italic>HLA\u2010DRB1*04<\/jats:italic>high\u2010resolution typing. Our results showed a strong association between<jats:italic>HLA\u2010DRB1*04<\/jats:italic>\/<jats:italic>DRB1*04:05<\/jats:italic>alleles and RA presence, which persisted after correcting for multiple comparisons (<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>&lt; 10\u22123,<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>= 0.020, respectively), in contrast to the protective effect of<jats:italic>HLA\u2010DRB1*04:03<\/jats:italic>allele (<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>= 15.2 \u00d7 10\u22124). However, increased frequency of<jats:italic>DQB1*05<\/jats:italic>(<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>= 0.020) and decreased frequency of<jats:italic>DRB1*04:03<\/jats:italic>subtype (<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>= 0.032) were seen in RF+ patients than controls. Moreover, when RA patients were compared to controls,<jats:italic>DRB1*04\u2010DQB1*03<\/jats:italic>haplotype was associated with RA susceptibility in Tunisians (<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>= 16.8 \u00d7 10\u22125), independently of RF status. Conversely,<jats:italic>DRB1*01<\/jats:italic>allele and<jats:italic>DRB1*01\u2010DQB1*05<\/jats:italic>haplotype was highly present in RF+<jats:italic>vs<\/jats:italic>RF\u2212 groups (<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>&lt; 10\u22123,<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>= 5.6 \u00d7 10\u22123, respectively) and seems to be linked to seropositivity. Investigation of HLA class II alleles and haplotypes association with RA susceptibility with secondary Sj\u00f6gren's syndrome (sSS) showed a predisposing effect of<jats:italic>DRB1*04<\/jats:italic>(<jats:italic>P<jats:sub>c<\/jats:sub><\/jats:italic>&lt; 10\u22123) and<jats:italic>DRB1*04\u2010DQB1*03<\/jats:italic>haplotype when RA with sSS\/without sSS groups were compared to healthy controls. Our results confirms the association of<jats:italic>HLA\u2010DRB1*04<\/jats:italic>, specifically<jats:italic>HLA\u2010DRB1*04:05<\/jats:italic>subtype, and<jats:italic>DRB1*04\u2010DQB1*03<\/jats:italic>haplotype with RA susceptibility in Tunisians, independently of seropositivity or the sSS presence.<\/jats:p>","DOI":"10.1111\/tan.12855","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T11:21:14Z","timestamp":1472728874000},"page":"100-109","source":"Crossref","is-referenced-by-count":20,"title":["HLA DRB1\/DQB1 alleles and DRB1\u2010DQB1 haplotypes and the risk of rheumatoid arthritis in Tunisians: a population\u2010based case\u2013control study"],"prefix":"10.1111","volume":"88","author":[{"given":"A.","family":"Lagha","sequence":"first","affiliation":[{"name":"Laboratory of Micro\u2010Organisms and Active Biomolecules El Manar University, University of Sciences of Tunis Tunis Tunisia"},{"name":"Department of Immunology Military Hospital of Tunis Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Messadi","sequence":"additional","affiliation":[{"name":"Laboratory of Micro\u2010Organisms and Active Biomolecules El Manar University, University of Sciences of Tunis Tunis Tunisia"},{"name":"Department of Immunology Military Hospital of Tunis Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Boussaidi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Habib Thameur Hospital Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kochbati","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Habib Thameur Hospital Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Tazeghdenti","sequence":"additional","affiliation":[{"name":"Laboratory of Micro\u2010Organisms and Active Biomolecules El Manar University, University of Sciences of Tunis Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Ghazouani","sequence":"additional","affiliation":[{"name":"Department of Immunology Military Hospital of Tunis Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Y.","family":"Almawi","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Arabian Gulf University Manama Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Yacoubi\u2010Loueslati","sequence":"additional","affiliation":[{"name":"Laboratory of Micro\u2010Organisms and Active Biomolecules El Manar University, University of Sciences of Tunis Tunis 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