Complement activation profile in primary immune thrombocytopenia: Its association with PA-IgM, increased platelet turnover and clinical outcomes

Abstract

Abstract Background: Complement activation in primary immune thrombocytopenia (ITP) has been reported, but its clinical relevance in individual patients remains poorly understood. Objective: To clarify the relationship between complement activation and various biomarkers and clinical characteristics in patients with ITP. Methods: Forty ITP patients were enrolled. Platelet-bound C1q, C3d, and C4d were quantified by flow cytometry. Levels of platelet-associated IgG and IgM, autoantibody specificity, and plasma complement components including the active/total C1s ratio were assessed. Relationships between complement activation and these parameters were analyzed. Clinical data including treatment line, medication burden, and fatigue score (FACIT-Fatigue) were also examined. Results: We classified ITP patients into three groups according to platelet-bound C1q, C3d, and C4d levels: all negative (Cluster 1), elevated C1q with negative-to-low C3d and C4d (Cluster 2), and high C3d and C4d (Cluster 3). PA-IgM was mostly detected in Cluster 3, and PA-IgG in Clusters 2 and 3. Heavily treated cases were more frequent in Clusters 2 and 3. Complement deposition correlated with an increased percentage of immature platelet fraction. No significant associations were found between complement activation and platelet-associated GPIIb/IIIa or GPIb/IX antibodies, the plasma C1s ratio, or the fatigue score. Conclusions: We identified three groups of ITP patients based on the platelet complement activation profile. This profile was associated with immunoglobulin classes of platelet-associated autoantibodies and treatment burden. Our data also suggest that markedly increased platelet turnover may be a characteristic of ITP involving complement activation.