title: Sulfasalazine Treatment Suppresses the Formation of HLA-B27 Heavy Chain Homodimer in Patients with Ankylosing Spondylitis.
abstract: Human leukocytic antigen-B27 heavy chain (HLA-B27 HC) has the tendency to fold slowly, in turn gradually forming a homodimer, (B27-HC)₂ via a disulfide linkage to activate killer cells and T-helper 17 cells and inducing endoplasmic reticulum (ER) stress to trigger the IL-23/IL-17 axis for pro-inflammatory reactions. All these consequences lead to the pathogenesis of ankylosing spondylitis (AS). Sulfasalazine (SSA) is a common medication used for treatment of patients with AS. However, the effects of SSA treatment on (B27-HC)₂ formation and on suppression of IL-23/IL-17 axis of AS patients remain to be determined. In the current study, we examine the (B27-HC)₂ of peripheral blood mononuclear cells (PBMC), the mean grade of sarcoiliitis and lumbar spine Bath Ankylosing Spondylitis Radiology Index (BASRI) scores of 23 AS patients. The results indicated that AS patients without (B27-HC)₂ on PBMC showed the lower levels of mean grade of sarcoiliitis and the lumbar spine BASRI scores. In addition, after treatment with SSA for four months, the levels of (B27-HC)₂ on PBMCs were significantly reduced. Cytokines mRNA levels, including TNFα, IL-17A, IL-17F and IFNγ, were also significantly down-regulated in PBMCs. However, SSA treatment did not affect the levels of IL-23 and IL-23R mRNAs.
authors.affiliation: Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan. df928039@tzuchi.com.tw.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Yu
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan. dm252940@tzuchi.com.tw.|School of Medicine, Tzu Chi University, Hualien 97004, Taiwan. dm252940@tzuchi.com.tw.
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Lu
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan. hky0919@yahoo.com.tw.|School of Medicine, Tzu Chi University, Hualien 97004, Taiwan. hky0919@yahoo.com.tw.
authors.forename: Kuang-Yung
authors.initials: KY
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Health Science, Fooyin University, Kaohsiung 83102, Taiwan. estrus@mail2000.com.tw.
authors.forename: Hsien-Lu
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan. df897226@tzuchi.com.tw.
authors.forename: Su-Qin
authors.initials: SQ
authors.lastname: Liu
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 62102, Taiwan. biohbh@ccu.edu.tw.
authors.forename: Hsien-Bin
authors.initials: HB
authors.lastname: Huang
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan. Q12015@tzuchi.com.tw.|School of Medicine, Tzu Chi University, Hualien 97004, Taiwan. Q12015@tzuchi.com.tw.
authors.forename: Ning-Sheng
authors.initials: NS
authors.lastname: Lai
mesh_terms: D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression; D015796:HLA-B27 Antigen / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D055503:Protein Multimerization; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D012460:Sulfasalazine / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D015796:HLA-B27 Antigen; D012460:Sulfasalazine
keywords: HLA-B27 homodimer; ankylosing spondylitis; mean grade of sarcoiliitis and lumbar spine BASRI scores; sulfasalazine