Screening for type II hereditary angioedema-the "poor man's c1-inhibitor function"

Ankur Kumar Jindal; Valerie Chiang; Prabal Barman; Archan Sil; Sanchi Chawla; Elaine Y L Au; Amit Rawat; Philip H Li

doi:10.1016/j.jacig.2023.100179

Screening for type II hereditary angioedema-the "poor man's c1-inhibitor function"

J Allergy Clin Immunol Glob. 2023 Oct 13;3(1):100179. doi: 10.1016/j.jacig.2023.100179. eCollection 2024 Feb.

Authors

Ankur Kumar Jindal¹, Valerie Chiang², Prabal Barman¹, Archan Sil¹, Sanchi Chawla¹, Elaine Y L Au², Amit Rawat¹, Philip H Li³

Affiliations

¹ Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
² Division of Clinical Immunology, Department of Pathology, Pokfulam, Hong Kong.
³ Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong.

Abstract

Background: Hereditary angioedema (HAE) is a rare genetic disease. Patients with type II HAE have normal or elevated C1-inhibitor (C1-INH) levels but C1-INH protein is dysfunctional. C1-INH function requires careful sample handling and technical expertise and may account for the lack of diagnosed patients with type II HAE in resource-limited countries.

Objective: We sought to assess the diagnostic performance of elevated C1-INH levels in diagnosing type II HAE.

Methods: All patients with confirmed type II HAE in Hong Kong and India were analyzed. Diagnosis was confirmed by persistent low C1-INH function and/or pathogenic SERPING1 gene mutations. Their C1-INH levels were compared with those of matched controls.

Results: A total of 31 (14 Chinese, 17 Indian) patients with type II HAE and 31 matched controls were analyzed. Overall, 77.4% (24/31) of patients with type II HAE had elevated C1-INH levels compared with 38.7% (12 of 31) of controls (odds ratio, 2.00; 95% CI, 1.34-2.98; P = .017). C1-INH levels in patients with type II HAE were significantly higher than in controls (52.2 ± 20.0 mg/dL vs 29.1 ±3.6 mg/dL; P < .001). Findings were consistent when C1-INH values in the Chinese and Indian subgroups were analyzed separately. Receiver-operating characteristic curve demonstrated excellent performance for elevated C1-INH levels to diagnose patients with type II HAE with an area under the curve of 0.953 (95% CI, 0.941-0.992; P < .001). Positive and negative predictive values of both a low C4 and an elevated C1-INH level for patients with type II HAE were 100% and 82.9%, respectively.

Conclusions: Low C4 and elevated C1-INH levels may be considered as a screening tool for type II HAE, especially in countries where C1-INH function testing is not readily available.

Keywords: C1 inhibitor; function; hereditary angioedema; level; screening; type 2 HAE.