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Associations between HLA-B27 subtypes and outcomes in Thai children with enthesitis-related arthritis

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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.

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Availability of data and material

The datasets analyzed during the current study are not publicly available due to the confidentiality agreement of the data with the participants but are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Acknowledgements

The authors thank the Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, for funding support (RF_60054); Ms. Tasanee Mongkolsuk for molecular typing of the HLA-B27 subtypes; Ms. Sukanya Siriyotha and Mr. Nattawut Unwanatham, Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, for performing the statistical analysis. We thank Anne M. O'Rourke, Ph.D., from Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study was funding by the Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (RF_60054).

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Authors and Affiliations

  1. Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand

    Soamarat Vilaiyuk & Butsabong Lerkvaleekul

  2. Histocompatibility & Immunogenetics Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Duangtawan Thammanichanond

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  1. Soamarat Vilaiyuk
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Contributions

Soamarat Vilaiyuk, Butsabong Lerkvaleekul, and Duangtawan Thammanichanond contributed to the study conception and design. Soamarat Vilaiyuk performed material preparation, data acquisition, and data analysis. Soamarat Vilaiyuk wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Soamarat Vilaiyuk.

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The study was approved by the Research and Ethics Committee of the Faculty of Medicine Ramathibodi Hospital, and was carried out in accordance with the Declaration of Helsinki (ID 12–59-07). Written informed consent was obtained from patients and their legal parents/guardians prior to enrollment.

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Vilaiyuk, S., Lerkvaleekul, B. & Thammanichanond, D. Associations between HLA-B27 subtypes and outcomes in Thai children with enthesitis-related arthritis. Clin Rheumatol 41, 203–212 (2022). https://doi.org/10.1007/s10067-021-05875-5

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