Work

On a quest for fingerprints of crystalglobulinemia on platelets and endothelium

Year: 2025

Type: article

Abstract: Crystalglobulinemia is a rare plasma cell dyscrasia characterized by the crystallization of monoclonal proteins within the systemic vasculature and tissues, leading to occlusive vasculopathy, nephropathy, and tissue ischemia. We investigated platelet and endothelial activation status in a patient with crystalglobulinemia presenting with thrombotic events and acute kidney injury before and after anticlonal therapy. Platelet function assessment revealed the presence of procoagulant platelets, characterized by phosphatidylserine exposure and increased P-selectin expression in the absence of external stimuli. This phenotype was reversed by ex vivo calcium chelation. Furthermore, evidence supports FcγRIIA-mediated platelet activation by crystal complexes. Platelet proteomic analysis demonstrated upregulation of complement-related proteins, apolipoproteins, and proteins involved in platelet activation pathways. In addition, crystal proteomic analysis identified immunoglobulin heavy constant gamma-1 and albumin in a 1:2 ratio. Endothelial gene expression was evaluated using real-time polymerase chain reaction after coculturing the patient's serum, isolated platelets, and citrated platelet-poor plasma with a serum-starved EA.hy926 endothelial monolayer. The patient's serum increased endothelial gene expression of ICAM-1 and ADAMTS13, whereas VCAM-1 and E-selectin were significantly reduced compared with participants, a phenotype typically observed under high shear stress conditions. Platelet and endothelial dysfunction correlated with disease activity and demonstrated partial reversal after treatment, highlighting potential implications for disease monitoring and therapeutic targeting.

Source: Blood Vessels Thrombosis & Hemostasis

DOI: 10.1016/j.bvth.2025.100134