Population-Specific HLA Profiles in Generalised Pustular Psoriasis in Sarawak, Malaysia

Genetic studies mutations (IL36RN, CARD14 and AP1S3) account for only 28.6% of generalised pustular psoriasis (GPP) leaving much of its pathogenesis remained to be elucidated. Emerging evidence suggests Th17-mediated inflammation, potentially driven by specific HLA class alleles, may underlie dysregulated IL-36 signalling. This study explores the genotypic and phenotypic features of autochthonous GPP in Sarawak. A cross-sectional case-control study was conducted in Sarawak's three main dermatology centres. GPP patients (n = 43) fulfilling ERASPEN criteria between 1997 and June 2024 were included (23 with GPP alone); 20 with concomitant psoriasis vulgaris. HLA genotyping (HLA-A, -B, -C, -DR) was performed via polymerase chain reaction and sequence-specific oligonucleotide probe hybridisation (PCR-SSO) methods at the Institute of Medical Research (IMR). HLA frequencies were compared to 90 Sarawakian controls from Malaysian Stem Cell Registry. Female predominance was noted (1:4.4). Median age at GPP onset was 29 years. Family history of psoriasis was reported in 30.2%, with 16% females developing GPP during pregnancy. Treatment responses: corticosteroids (100%), ciclosporin (82.1%), acitretin (60%) and methotrexate (50%). While biologics were effective in 10 patients. Common alleles included HLA-DRB1*12:02, HLA-A*11:01 and HLA-C*07:02 while HLA-C06:02 was not observed. HLA-A*02:07 and HLA-B*46:01 were observed only in concomitant psoriasis patients. HLA-A*11:02 was seen in patients with ciclosporin non-response, HLA-A*24:02 in those with poorer responses to acitretin and methotrexate and HLA-B*38:02 in psoriatic arthritis. Lower frequencies of HLA-B*35:05 and HLA-C*04:01 were observed among Dayak patients. The absence of HLA-C*06:02 and variation in allele frequencies in this cohort may reflect population-specific patterns but require validation in larger studies.