Bullous Pemphigoid Severity and Levels of Antibodies to BP180 and BP230

Importance The correlation between serum levels of autoantibodies against bullous pemphigoid (BP) antigens 180 (BP180) and 230 (BP230) with BP disease severity is unclear. Objective To investigate the correlation of anti-BP180 and anti-BP230 immunoglobulin G (IgG) antibody levels with BP disease severity. Data Sources A search was performed of the Cochrane Central Register of Controlled Trials, Embase, and PubMed databases from their respective inception to April 11, 2024. Study Selection Studies evaluating the correlation between serum levels of anti-BP180 or anti-BP230 IgG measured using enzyme-linked immunosorbent assay (ELISA) and disease severity assessed per the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) or BP Disease Area Index (BPDAI) were included. No language or geographic restrictions were imposed. Nearly 0.4% of initially identified studies met the selection criteria. Data Extraction and Synthesis One researcher extracted data and another researcher confirmed data. The risk of bias was independently assessed by these researchers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, with discrepancies resolved by discussion with a third researcher. A random-effects model meta-analysis and a subgroup analysis were conducted based on the ELISA kit manufacturers. Main Outcomes and Measures Pooled correlation coefficients of antibody levels with ABSIS and BPDAI. Results In all, 14 studies with 1226 participants were analyzed. The risk of bias of included studies was generally low. The meta-analysis found anti-BP180 autoantibody levels showed moderate correlation with objective BPDAI ( r = 0.56; 95% CI, 0.46-0.64) at baseline, strong correlation ( r = 0.63; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation ( r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. Anti-BP180 autoantibody levels also showed moderate correlation ( r = 0.52; 95% CI, 0.39-0.62) with ABSIS at baseline, strong correlation ( r = 0.62; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation ( r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. By contrast, anti-BP230 autoantibody levels showed no association with objective BPDAI and ABSIS at diagnosis and follow-up. The subgroup analysis found similar results when using different ELISA kits. Conclusions and Relevance The findings of this systematic review and meta-analysis indicated that anti-BP180 autoantibody levels may serve as an adjunctive tool for monitoring BP disease severity and guiding clinical care for patients with BP.