Susceptibility Genes and HLA for Cold Medicine-Related SJS/TEN with SOC

Abstract

We investigated the genetic predisposition for the pathogenesis of Stevens-Johnson syndrome/epidermal necrolysis with severe ocular complications (SJS/TEN with SOC). Cold medicines (CMs) including multi-ingredient cold-medications and non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in the development of SJS/TEN with SOC. Studies on the association between HLA genotypes and CM-related SJS/TEN with SOC (CM-SJS/TEN with SOC) revealed an association with HLA-A*02:06 in the Japanese; it may be a marker in Koreans. HLA-B*44:03 was associated with the Japanese, Thais, and Indians; in Brazilians of European ancestry, it may be a positive marker. PTGER3 is a susceptibility gene; HLA-A*02:06 and PTGER3 polymorphisms exerted additive effects in Japanese and Korean patients. A genome-wide association study showed that IKZF1 was associated with the Japanese. A meta-analysis including Japanese, Koreans, Indians, and Brazilians also revealed an association between CM-SJS/TEN with SOC and IKZF1. The upregulation of hsa-miR-628-3p in the plasma of SJS/TEN with SOC patients may suppress the expression of TLR3 and innate immune-related genes. Not only CMs but also the interaction of TLR3, PTGER3, IKZF1, and HLA and maybe some microbial infections are necessary for the onset of SJS/TEN with SOC.

Keywords: HLA; IKZF1; PTGER3; Stevens–Johnson syndrome; TLR3; Toxic epidermal necrolysis; cold medicine; severe ocular complications.

FIGURE 1

Summary of the association between HLA types and CM-related SJS/TEN with SOC. HLA-B*44:03 was significantly associated with CM-related SJS/TEN with SOC in Japanese, Brazilian, Indian, and Thai populations. HLA-A*02:06 was significantly associated with CM-related SJS/TEN with SOC in Japanese and Korean patients (OR: odds ratio OR).

FIGURE 2

Abnormal innate immunity may be involved in the development of SJS/TEN with SOC.