Chemiluminescence Immunoassay and Enzyme-Linked Immunosorbent Assay in the Diagnosis of Pemphigoid and Pemphigus: A Comparative Study.

Autoimmune bullous diseases (AIBDs), including pemphigus vulgaris (PV), pemphigus foliaceus (PF), and bullous pemphigoid (BP), are mediated by autoantibodies against desmogleins (DSG1, DSG3) or hemidesmosomal proteins (BP180, BP230). While enzyme-linked immunosorbent assay (ELISA) is commonly applied for antibody detection, chemiluminescent immunoassay (CLIA) offers advantages such as a broader dynamic range and higher automation. To compare the diagnostic performance of CLIA and ELISA for detecting autoantibodies in patients with AIBDs, we collected 255 serum samples (92 controls, 84 BP, 69 PV, 10 PF) and 85 blister fluid samples (42 controls, 43 BP). Serum was tested for anti-BP180, anti-BP230, anti-DSG1, and anti-DSG3 antibodies using both assays; blister fluid was tested for anti-BP180 and anti-BP230. Using established cut-offs, the assays demonstrated good diagnostic accuracy for anti-BP180, anti-DSG1, and anti-DSG3 in serum, and excellent concordance (>90%). Receiver operating characteristic analysis revealed acceptable to excellent diagnostic value for both sample types, with CLIA generally achieving a higher area under the curve. Spearman's correlation and linear regression analyses confirmed moderate to strong agreement between the two methods. In conclusion, CLIA showed strong concordance with and comparable diagnostic accuracy to ELISA for AIBD serodiagnosis. Furthermore, this is the first study to evaluate CLIA for autoantibody detection in blister fluid from BP patients, demonstrating that blister fluid may serve as a less invasive sample type for diagnosis. Our cut-off analysis in a treated cohort also suggested that manufacturer-recommended thresholds may yield false-negative results, highlighting the need for population-specific reference intervals.