The World Allergy Organization journal · 2026
Development and validation of a clinically applicable biomarker panel for identifying autoimmune type IIb chronic spontaneous urticaria.
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Ji Jiang, Chen Lu, Ma Ni, Yao Yuxu, Zhang Chuqiao, Li Enze, Jiao Qingqing
Аннотация
BACKGROUND: Chronic spontaneous urticaria (CSU) includes 2 autoimmune endotypes, type I (autoallergic) and type IIb (autoimmune), which differ in pathogenesis and treatment response. However, practical criteria for distinguishing these endotypes in routine clinical practice remain limited.
OBJECTIVE: This study aimed to evaluate whether combinations of readily available clinical parameters facilitate identification of probable type IIb CSU.
METHODS: A total of 125 CSU patients were evaluated using 3 diagnostic combinations: (1) high IgG anti-thyroid peroxidase antibodies (IgG-anti-TPO) with low total IgE; (2) high IgG-anti-TPO with a positive autologous serum skin test (ASST+); and (3) low total IgE with ASST+. Clinical and laboratory features were compared between presumed endotypes. Serum cytokine profiles were analyzed and validated in an independent cohort of 40 patients. A predictive graphical model integrating clinical and laboratory variables was developed.
RESULTS: All 3 combinations identified patient subsets with features compatible with type IIb CSU, including trends toward higher disease activity (UAS7), peripheral eosinopenia and basopenia. The combination of high IgG-anti-TPO with ASST positivity was associated with the most comprehensive type IIb-compatible features. Cytokine profiles also differed between endotypes: serum IL-6 tended to be lower in possible type IIb CSU, whereas IL-17 A and TNF-α tended to be higher, compared with the remaining CSU patients. These patterns were directionally supported in the independent validation cohort. The predictive nomogram model demonstrated good discriminatory performance.
CONCLUSIONS: Combinations of IgG-anti-TPO, total IgE, and ASST provide practical reference tools for identifying probable type IIb CSU, with high IgG-anti-TPO plus ASST positivity showing the highest clinical relevance. Distinct cytokine patterns further support endotype-related immune differences and may aid individualized management.
OBJECTIVE: This study aimed to evaluate whether combinations of readily available clinical parameters facilitate identification of probable type IIb CSU.
METHODS: A total of 125 CSU patients were evaluated using 3 diagnostic combinations: (1) high IgG anti-thyroid peroxidase antibodies (IgG-anti-TPO) with low total IgE; (2) high IgG-anti-TPO with a positive autologous serum skin test (ASST+); and (3) low total IgE with ASST+. Clinical and laboratory features were compared between presumed endotypes. Serum cytokine profiles were analyzed and validated in an independent cohort of 40 patients. A predictive graphical model integrating clinical and laboratory variables was developed.
RESULTS: All 3 combinations identified patient subsets with features compatible with type IIb CSU, including trends toward higher disease activity (UAS7), peripheral eosinopenia and basopenia. The combination of high IgG-anti-TPO with ASST positivity was associated with the most comprehensive type IIb-compatible features. Cytokine profiles also differed between endotypes: serum IL-6 tended to be lower in possible type IIb CSU, whereas IL-17 A and TNF-α tended to be higher, compared with the remaining CSU patients. These patterns were directionally supported in the independent validation cohort. The predictive nomogram model demonstrated good discriminatory performance.
CONCLUSIONS: Combinations of IgG-anti-TPO, total IgE, and ASST provide practical reference tools for identifying probable type IIb CSU, with high IgG-anti-TPO plus ASST positivity showing the highest clinical relevance. Distinct cytokine patterns further support endotype-related immune differences and may aid individualized management.