Soamarat Vilaiyuk1, Butsabong Lerkvaleekul2, Duangtawan Thammanichanond3. 1. Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand. soamarat21@hotmail.com. 2. Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand. 3. Histocompatibility & Immunogenetics Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Abstract
OBJECTIVE: Expression of human leukocyte antigen B27 (HLA-B27) has been identified as a predictor of severe disease in enthesitis-related arthritis (ERA) patients. However, the associations between HLA-B27 subtypes and outcomes of this disease are still unclear. Here, we examined the distributions of HLA-B27 subtypes among ERA patients and the associations with disease outcomes. METHODS: This was a historical cohort study of ERA patients. Patients were followed from diagnosis to the most recent visit. Relationships between outcomes and the HLA-B27 subtype were assessed by mixed-effect regression, Kaplan-Meier survival, and Cox proportional hazards regression analyses. RESULTS: Of the 66 ERA patients, 50 HLA-B27-positive (86% male) and 16 HLA-B27-negative (69% male) patients were included in this study. Patients with HLA-B27-positive were classified into HLA-B*27:04-positive (84%), including combined HLA-B*27:04 and HLA-B*27:07 (2%), and HLA-B*27:04-negative (16%), including HLA-B*27:05 (10%), HLA-B*27:06 (2%), HLA-B*27:07 (2%), and HLA-B*27:15 (2%). HLA-B*27:04-positive (83.3%) and HLA-B*27:04-negative patients (100%) had refractory disease more than HLA-B27-negative patients (37.5%, p = 0.001). HLA-B*27:04-negative patients (57%, 1.73 years) had relapsing disease more and earlier than HLA-B*27:04-positive (35%, 5.54 years) and HLA-B27-negative patients (40%, 6.92 years; p < 0.001). Furthermore, HLA-B*27:04-negative was predictors of refractory disease (HR 4.56, 95%CI 1.40-14.87; p = 0.012) and relapsing disease (HR 3.80, 95% CI 1.18-12.30; p = 0.026). The duration before anti-tumor necrosis factor treatment initiation > 1 year was also a predictor of refractory disease (HR 116.08, 95% CI 14.67-918.26; p < 0.001). CONCLUSION: HLA-B*27:04 was the most common HLA-B27 subtype in Thai ERA patients. HLA-B*27:04-negative was associated with more unfavorable outcomes than HLA-B*27:04-positive and HLA-B27-negative patients. Key Points • Most ERA patients in Thailand had HLA-B27-positive, and HLA-B*27:04 was the most common HLA-B27 allele in these patients. • The outcomes of ERA were associated with the presence of HLA-B27 and its subtypes. • HLA-B*27:04-negative patients had unfavorable outcomes, including refractory and relapsing disease, compared to HLA-B*27:04-positive and HLA-B27-negative patients.
OBJECTIVE: Expression of human leukocyte antigen B27 (HLA-B27) has been identified as a predictor of severe disease in enthesitis-related arthritis (ERA) patients. However, the associations between HLA-B27 subtypes and outcomes of this disease are still unclear. Here, we examined the distributions of HLA-B27 subtypes among ERA patients and the associations with disease outcomes. METHODS: This was a historical cohort study of ERA patients. Patients were followed from diagnosis to the most recent visit. Relationships between outcomes and the HLA-B27 subtype were assessed by mixed-effect regression, Kaplan-Meier survival, and Cox proportional hazards regression analyses. RESULTS: Of the 66 ERA patients, 50 HLA-B27-positive (86% male) and 16 HLA-B27-negative (69% male) patients were included in this study. Patients with HLA-B27-positive were classified into HLA-B*27:04-positive (84%), including combined HLA-B*27:04 and HLA-B*27:07 (2%), and HLA-B*27:04-negative (16%), including HLA-B*27:05 (10%), HLA-B*27:06 (2%), HLA-B*27:07 (2%), and HLA-B*27:15 (2%). HLA-B*27:04-positive (83.3%) and HLA-B*27:04-negative patients (100%) had refractory disease more than HLA-B27-negative patients (37.5%, p = 0.001). HLA-B*27:04-negative patients (57%, 1.73 years) had relapsing disease more and earlier than HLA-B*27:04-positive (35%, 5.54 years) and HLA-B27-negative patients (40%, 6.92 years; p < 0.001). Furthermore, HLA-B*27:04-negative was predictors of refractory disease (HR 4.56, 95%CI 1.40-14.87; p = 0.012) and relapsing disease (HR 3.80, 95% CI 1.18-12.30; p = 0.026). The duration before anti-tumor necrosis factor treatment initiation > 1 year was also a predictor of refractory disease (HR 116.08, 95% CI 14.67-918.26; p < 0.001). CONCLUSION: HLA-B*27:04 was the most common HLA-B27 subtype in Thai ERA patients. HLA-B*27:04-negative was associated with more unfavorable outcomes than HLA-B*27:04-positive and HLA-B27-negative patients. Key Points • Most ERA patients in Thailand had HLA-B27-positive, and HLA-B*27:04 was the most common HLA-B27 allele in these patients. • The outcomes of ERA were associated with the presence of HLA-B27 and its subtypes. • HLA-B*27:04-negative patients had unfavorable outcomes, including refractory and relapsing disease, compared to HLA-B*27:04-positive and HLA-B27-negative patients.
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