Genetics and Omics Analysis of Autoimmune Skin Blistering Diseases

Abstract

Autoimmune blistering diseases (AIBDs) of the skin are characterized by autoantibodies against different intra-/extracellular structures within the epidermis and at the basement membrane zone (BMZ). Binding of the antibodies to their target antigen leads to inflammation at the respective binding site and degradation of these structures, resulting in the separation of the affected skin layers. Clinically, blistering, erythema and lesions of the skin and/or mucous membranes can be observed. Based on the localization of the autoantigen, AIBDs can be divided into pemphigus (intra-epidermal blistering diseases) and pemphigoid diseases (sub-epidermal blistering diseases), respectively. Although autoantigens have been extensively characterized, the underlying causes that trigger the diseases are still poorly understood. Besides the environment, genetic factors seem to play an important role in a predisposition to AIBDs. Here, we review currently known genetic and immunological mechanisms that contribute to the pathogenesis of AIBDs. Among the most commonly encountered genetic predispositions for AIBDs are the HLA gene region, and deleterious mutations of key genes for the immune system. Particularly, HLA class II genes such as the HLA-DR and HLA-DQ alleles have been shown to be prevalent in patients. This has prompted further epidemiological studies as well as unbiased Omics approaches on the transcriptome, microbiome, and proteome level to elucidate common and individual genetic risk factors as well as the molecular pathways that lead to the pathogenesis of AIBDs.

Assessment of the Characteristics and Associated Factors of Infectious Complications in Bullous Pemphigoid

“…Bullous pemphigoid (BP) is an autoimmune bullous skin disorder commonly identified in the elderly population. It is an autoantibody-induced cutaneous inflammatory disease against BP180 or BP230 at the dermal-epidermal junctions ( 1 , 2 ). The annual incidence rate of BP has been increasing steadily in the elderly and general populations ( 3 ), and the BP patients were reported to have a significantly increased risk of death compared to the control subjects ( 4 – 7 ).…”

Pemphigus associated with ipilimumab therapy

“…Investigation of the patient’s human leukocyte antigen (HLA) typing revealed DQB1*0302, DQA1*0301, and DRB1*04, all of which are associated with pemphigus vulgaris (PV) and DRB1*04, which is also associated with pemphigus foliaceous (PF) (Table 2). 1‐6 DQB1*0302 is most strongly associated with PV, especially a severe form in females 7 . Class II HLA alleles are reportedly most associated with PV and PF, and our patient had three associated class II HLA alleles 2 …”

A Comparative Analysis of CD32A and CD16A Polymorphisms in Relation to Autoimmune Responses in Pemphigus Diseases and Subepithelial Autoimmune Blistering Disorders

“…It was postulated that these polymorphisms affect receptor signaling and may be associated with ABDs susceptibility. Recent investigative efforts included the identification of mutations in genes encoding immunological molecules and their possible associations with pathological autoimmune response in various dermatoses [10,25]. Previous reports indicated that CD32B polymorphisms may be associated with systemic lupus erythematosus [26].…”