Lower Serum SCCA2 Detectability in Chronic Spontaneous Compared with Chronic Inducible Urticaria: A Prospective Observational Study

Background/Objectives: Squamous cell carcinoma antigen 2 (SCCA2; SERPINB4) is an IL-4/IL-13-inducible epithelial serpin that can inhibit human mast-cell chymase, providing a potential link to mast-cell-mediated inflammation. To our knowledge, SCCA2 has not previously been studied in chronic urticaria; we hypothesized that circulating SCCA2 would differ among chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), and healthy controls. Methods: This prospective, single-center observational study included 36 patients with CSU, 35 with provocation-confirmed CIndU, and 45 healthy controls; atopic or allergic diseases were excluded in all groups. Baseline blood sampling was performed before treatment initiation. Serum SCCA2 was measured by ELISA. Because quantification below the lower limit of quantification (LLOQ, 0.16 ng/mL) was not validated, primary interpretation used assay-defined categories based on the limit of detection (LOD, 0.09 ng/mL) and LLOQ; continuous analyses were exploratory. Results: SCCA2 detectability was 22.2% in CSU, 62.9% in CIndU, and 68.9% in controls. Detectability was lower in CSU than in CIndU and controls (Holm-adjusted p = 0.0015 and p < 0.001), whereas CIndU and controls did not differ (p = 0.637). Among patients, below-LOD SCCA2 was associated with CSU (OR 5.92, 95% CI 2.09–16.81) and remained associated after adjustment for total IgE, eosinophil count, and CRP (aOR 4.73, 95% CI 1.59–14.08; p = 0.005). Conclusions: Serum SCCA2 showed a CSU-associated low-detectability pattern, whereas CIndU and controls did not differ significantly. Because most estimates were below the LLOQ, findings represent differences in assay-defined detectability rather than validated concentrations. Independent validation is required.