A systematic review and meta-analysis found that serum levels of anti-BP180 autoantibodies showed moderate to strong correlation with bullous pemphigoid disease severity, while anti-BP230 autoantibody levels demonstrated no significant correlation.

The study, published in JAMA Dermatology, analyzed data from 14 studies involving 1,226 participants to investigate the correlation between serum levels of anti-BP180 and anti-BP230 immunoglobulin G (IgG) antibodies and bullous pemphigoid (BP) disease severity as measured by standardized scoring systems.

The investigators conducted a comprehensive search of the Cochrane Central Register of Controlled Trials, Embase, and PubMed databases from their inception to April 11, 2024. The search yielded 3,629 records, with an additional eight articles provided by ELISA kit manufacturers. After removing duplicates and screening titles and abstracts, 79 potentially eligible studies were identified. Ultimately, 14 studies met the inclusion criteria.

The studies were included if they evaluated the correlation between serum levels of anti-BP180 or anti-BP230 IgG measured by enzyme-linked immunosorbent assay (ELISA) and disease severity assessed using Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) or Bullous Pemphigoid Disease Area Index (BPDAI). The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, with most included studies showing a generally low risk of bias.

A random-effects model meta-analysis was performed using the inverse variance method with restricted maximum-likelihood approach to estimate between-study variance. The strength of correlations was classified as very weak (0 to 0.19), weak (0.20 to 0.39), moderate (0.40 to 0.59), strong (0.60 to 0.79), and very strong (0.80 to 1.00).

Among the key findings were:

• Anti-BP180 IgG levels showed moderate correlation with BPDAI at baseline (r = 0.56, 95% confidence interval [CI] = 0.46–0.64), strong correlation at 3-month follow-up (r = 0.63, 95% CI = 0.39–0.79), and moderate correlation at 6-month follow-up (r = 0.53, 95% CI = 0.25–0.72).
• Similarly, anti-BP180 IgG levels demonstrated moderate correlation with ABSIS at baseline (r = 0.52, 95% CI = 0.39–0.62), strong correlation at 3-month follow-up (r = 0.62, 95% CI = 0.39–0.79), and moderate correlation at 6-month follow-up (r = 0.53, 95% CI = 0.25–0.72).
• Anti-BP230 IgG levels showed no statistically significant correlations with either BPDAI or ABSIS scores at diagnosis or during follow-up.
• Subgroup analysis revealed strong correlation between anti-BP180 IgG levels and the erosion/blister subcomponent of BPDAI (r = 0.68, 95% CI = 0.16–0.91) and moderate correlation with the urticaria/erythema/other subcomponent (r = 0.44, 95% CI = 0.23–0.61).
• Anti-BP180 IgG levels also correlated strongly with the skin subcomponent of ABSIS (r = 0.60, 95% CI = 0.49–0.69).

Additional findings from the study included:

• The meta-analysis found moderate correlation between anti-BP180 IgG levels and the number of new daily blisters (r = 0.41, 95% CI = 0.32–0.50) at baseline.
• Anti-BP180 IgG levels showed weak correlation with BPDAI pruritus score at baseline (r = 0.34, 95% CI = 0.22–0.45), strong correlation at 3-month follow-up (r = 0.62, 95% CI = 0.39–0.79), and moderate correlation at 6-month follow-up (r = 0.52, 95% CI = 0.25–0.72).
• The subgroup analysis based on ELISA kit manufacturers (Medical & Biological Laboratories or EUROIMMUN) found no statistically significant differences in the pooled correlation coefficients.
• Anti-BP180 IgG levels did not correlate with the mucosal subcomponent of BPDAI (r = 0.03, 95% CI = −0.12 to 0.17) or the oral mucosa (r = −0.02, 95% CI = −0.22 to 0.18) and oral discomfort (r = 0.12, 95% CI = −0.09 to 0.31) subcomponents of ABSIS.

The study also provided insights into the characteristics of the included studies:

• Six studies used ELISA kits manufactured by EUROIMMUN AG, seven studies used kits by Medical & Biological Laboratories, and one study did not specify the manufacturer.
• The average baseline BPDAI score of the included studies ranged from 10.0 to 52.5, indicating mild to moderate disease severity.
• The mean age of participants in the included studies ranged from 56.3 to 82.5 years.
• The percentage of patients with mucosal involvement varied widely among studies, ranging from 5.9% to 46.7%.

The investigators noted several limitations of the study, including the relatively high statistical heterogeneity in the correlation of anti-BP180 ELISA with BPDAI, although this was primarily caused by differences in the strength of correlation rather than statistical significance. Additionally, only one included study provided serial follow-up data on the correlation of autoantibody levels with BPDAI and ABSIS scores over time.

The authors declared having no competing interests.