Genetic Susceptibility in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease: A Case–Control Study

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Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease (SOS/VOD) is a severe complication of hematopoietic cell transplantation (HCT). Furthermore, emerging evidence suggests the potential role of complement activation and endothelial injury in SOS/VOD pathogenesis. In this study, we aimed to identify potential distinct pathogenic genetic variants between SOS/VOD and other endothelial injury syndromes following HCT, such as transplant-associated thrombotic microangiopathy (TA-TMA). For this aim, genomic DNA from 30 SOS/VOD patients and 30 controls with TA-TMA was analyzed. Using Next-Generation Sequencing (NGS), variants in complement-related genes (CFH, CFI, CFB, CFD, C3, CD55, C5, CD46, and thrombomodulin/THBD) and ADAMTS13 were examined. Out of 426 detected variants, 20 were classified as pathogenic. In SOS/VOD patients, variants were identified in ADAMTS13 (4), CFH (3), C3 (2), and CFB (1) genes. One of the variants has been recognized as the strongest genetic predictor of ADAMTS13 activity. Controls exhibited more variants in complement-related genes, particularly CFH, CFI, and C3. The genetic differences between SOS/VOD and TA-TMA highlight different pathogenic mechanisms, offering the potential for targeted risk assessment and therapy in HCT recipients.

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