The alternative complement pathway activation product Ba as a marker for transplant‐associated thrombotic microangiopathy
2019
BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) occurs after hematopoietic stem cell transplantation (HSCT) and is characterized by microvascular thrombosis and end-organ injury particularly of the kidneys. TA-TMA is challenging to diagnose and treat, which can lead to long-term complications and death in patients with severe disease. Studies have shown that genetic abnormalities of the alternative complement pathway (AP) are associated with TA-TMA. We hypothesized that patients with TA-TMA may generate elevated levels of the AP activation product, Ba, compared with HSCT patients without TA-TMA. PROCEDURE: We longitudinally measured plasma levels of complement activation products C3a, Ba, and C5a in 14 HSCT patients: 7 with TA-TMA and 7 without TA-TMA. We assessed renal function by calculating estimated glomerular filtration rate (eGFR) and correlated the extent of AP activation with renal dysfunction in both patient populations. RESULTS: The median days from HSCT to study enrollment were 154 (39-237) in the TA-TMA group and 84 (39-253) in the HSCT group without TA-TMA. Median Ba levels (ng/mL) at enrollment were 1096.9 (826.5-1562.0) in the TA-TMA group and 725.7 (494.7-818.9) in the HSCT group without TA-TMA (P = 0.007). Over the study duration, Ba levels inversely correlated with eGFR. There were no differences in C3a, C5a, or sC5b9 levels between the two populations at any measured interval. CONCLUSIONS: We conclude in this preliminary study that Ba protein may serve as a marker for TA-TMA, and furthermore, that components generated in the early phase of AP activation may be involved in the pathogenesis of renal endothelial injury in TA-TMA.
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