Diagnostic methods and strategies for autoimmune bullous diseases

Autoimmune bullous disease (AIBD), showing blistering lesions on the skin and/or mucous membranes, is characterized by autoantibodies against various structural molecules present in keratinocyte cell surfaces and epidermal basement membrane zone. In addition to the clinical and pathological features, identification of specific autoantibodies is essential for AIBD diagnosis, and therefore corresponding methods should be well summarized and popularized.

Currently, direct immunofluorescence using biopsy tissue specimen and indirect immunofluorescence using normal human skin, 1 M NaCl-split skin and rat bladder are primarily used to identify tissue-bound and circulating autoantibodies, respectively. Immunoblotting and enzyme-linked immunosorbent assay (ELISA) methods have been developed for detection of autoantibodies against AIBD autoantigens, including desmoglein 1, desmoglein 3, BP180, BP230, type VII collagen, laminin (LM) 332, integrin α6β4, p200 (LMγ1/LMβ4) and human serum albumin. In this review, we summarized the detailed laboratory protocols for AIBD diagnosis methods used in our three institutes (Kurume University and Osaka Metropolitan University in Japan, and Daqing Oilfield General Hospital in China) before 9 October 2024.

This review will benefit both clinical practitioners and basic researchers on AIBD. In the future, simpler and easier AIBD diagnostic algorithms using a smaller number of tests should be established.