Melanoma, with increasing annual incidence worldwide, is one of the deadliest cutaneous malignancies often treated with immunotherapy, which has led to commonly encountered immune-related adverse events (irAEs) including bullous pemphigoid (BP). The relation between an individual's HLA inheritance and risk in development of BP is well studied. The development of BP as an irAE in melanoma patients receiving immunotherapy is also well reported and considered to be related to the expression of BP180 in malignant melanoma. In presented work, the association of enriched presence of certain HLA alleles and haplotypes that increase risk of developing BP as an irAE has been investigated in seven cutaneous cancer patients who presented with immunotherapy-associated BP, diagnosed by skin biopsy and positive serology for anti-BP 180 autoantibody. Their HLA typing revealed an enriched presence of certain BP-related HLA alleles, and haplotypes, particularly HLA-DQB1*03:01, which was present in all seven patients, whilst its occurrence in the general population is very low. Additionally, some patients had more than one and in a few patients had the whole haplotype of BP related HLA. Not only can such enriched presence be considered a role in risk stratification to initiate or continue immunotherapy, but it may shed a light to existing disease genotypes that can become unmasked to phenotypic clinically presenting BP due to immunotherapy rather than just a random AE.
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