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The alternative complement pathway activation product Ba as a marker for transplant‐associated thrombotic microangiopathy
Author(s) -
Sartain Sarah,
Shubert Stacey,
Wu MengFen,
Wang Tao,
Martinez Caridad
Publication year - 2020
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28070
Subject(s) - thrombotic microangiopathy , medicine , complement system , renal function , gastroenterology , hematopoietic stem cell transplantation , eculizumab , thrombosis , microangiopathy , alternative complement pathway , transplantation , urology , immunology , disease , endocrinology , immune system , diabetes mellitus
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.