Complement activation profile in adult primary immune thrombocytopenia

ABSTRACT: Complement activation has been reported in primary immune thrombocytopenia (ITP); however, its clinical relevance remains poorly understood. This study aimed to clarify the association between complement activation and various biomarkers and the clinical characteristics of patients with ITP. A total of 40 patients with ITP were enrolled in this study. Platelet-bound C1q, C3d, and C4d were elevated in a substantial population of patients with ITP compared with healthy controls with highly variable titers. Hierarchical clustering analysis showed that patients with ITP could be classified into the following 3 groups according to their levels: all negative (cluster 1), elevated C1q with negative to low C3d and C4d (cluster 2), and high C3d and C4d (cluster 3). Platelet-associated (PA) immunoglobulin M (IgM) was detected mostly in cluster 3, and PA-IgG was detected in clusters 2 and 3. The number of cases refractory to first-line therapy increased in clusters 2 and 3. Complement deposition on the platelet surface correlated with an increased percentage of immature platelets. There was no significant association between complement activation and PA glycoprotein IIb/IIIa (GPIIb/IIIa) or PA-GPIb/IX antibodies, C1s ratio in the plasma, and fatigue score. Our results suggest that PA-IgG and PA-IgM contribute differentially to the complement activation profile on the platelet surface and are associated with increase in platelet turnover, characterizing a distinct subset of patients with ITP with complement activation. Our findings also may provide a rationale for stratifying patients in future clinical trials of complement-targeted therapies.