New Potential Biomarker Discovered for Skin Disease in Diabetics

INCREASED incidences of bullous pemphigoid (BP), the most common autoimmune blistering disorder, have been noted among patients prescribed dipeptidyl peptidase-4 inhibitory compounds (DPP-4i), a drug prescribed to treat Type II diabetes mellitus. Now, researchers have identified a type of human leukocyte antigen (HLA) that is associated with increased susceptibility to BP.

Characterised by itchy reddening of the skin and tense blisters covering the body, BP initiates autoimmune attacks on a type of collagen within the skin. The disorder exists in two distinct forms, inflammatory and non-inflammatory, with the latter exhibiting an increased prevalence in diabetic DPP-4i-taking patients. Until now, no risk factor triggering BP in diabetic DPP4i treatment had been identified. However, researchers from Hokkaido University Hospital, Sapparo, Japan, have uncovered a novel gene that could predict an individual’s risk of developing BP.

The team initiated their investigation by assessing 30 BP patients taking DPP-4i and examining their symptoms and autoantibodies to determine the disorder’s inflammatory state. HLA-genes were also analysed to ascertain white blood cell type, since HLA genotype can influence autoimmune disorders. The HLA-genes of 72 non-DPP-4i taking diabetic patients and 62 DPP-4i taking diabetic patients unaffected by BP were also analysed, in addition to HLA-genes from 873 people from the general Japanese population.

Results indicated that 70% of the diabetic DPP4i-administered BP patients had the non-inflammatory variant of the condition, and 86% of those patients’ HLA-genotypes included the gene HLA-DQB1*03:01. The prevalence of this HLA-gene was detected among 18% of the general population, 31% of non-BP patients receiving DPP-4i, and 26% of BP patients not receiving DPP4i. These genetic discoveries show that HLA-DQB1*03:01 is not linked to non-DPP4i-associated BP or Type II diabetes mellitus; however, it is strongly associated with BP development among patients receiving DPP-4i. “The gene could serve as a biomarker to help estimate the risk of developing BP when patients are administered with DPP-4i,” explained one of the study authors, Dr Hideyuki Ujiie, Hokkaido University Hospital.

Further studies are needed to elucidate the extent to which patients receiving DPP-4i develop BP. “The mechanism that connects the HLA gene and BP needs to be addressed to help prevent the development of the disease,” concluded Dr Ujiie.

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