Background: Chronic spontaneous urticaria (CU) is a common skin disorder, with an estimated prevalence of 0.5-1.8% in most populations. Around 30-50% of CU patients have an autoimmune etiology, with autoantibodies (autoAbs) against IgE, FcεRIα, and FcεRII/CD23. Although the in vivo autologous serum skin test (ASST) and in vitro histamine release/activation assay are the most frequently used screening methods, these two have many limitations and do not directly measure susceptible autoAbs. This study aimed to establish an in vitro rapid screening test using recombinant autoantigen FcεRIα(rFcεRIα) to improve the diagnosis of autoimmune urticaria.
Methods: Forty patients with CU and 20 healthy individuals were enrolled. After PCR-based cloning and the production of extracellular fragments of the FcεRIα protein using the E. coli expression system, serum autoAb to rFcεRIα was evaluated using in-house ELISA and rapid immunodot test.
Results: In ELISA-based detection, 14 out of 20 CU-ASST(+) patients exhibited anti- FcεRIα responses, whereas five of the 20 CU-ASST(-) and two of the 20 non-CU patients showed autoantibody background in the assay. For the immunodot test, 55% (11/20) of the CU-ASST(+) sera exhibited anti-FcεRIα reactivity. There was no false positive among the CU-ASST(-) and non-CU groups. Using clinical urticaria plus ASST(+) as the gold standard, in-house ELISA had 70% sensitivity, 82.5% specificity, and positive likelihood ratio of 4, while immunodot had 55% sensitivity, 100% specificity, and positive likelihood ratio >55.
Conclusions: This study has developed a rapid immunodot method with high specificity for detecting autoAb to FcεRIαin patients with CU. Preliminary data indicates that this immunodot technique has the potential to be a routine diagnostic assay for autoimmune CU.