The alternative complement pathway activation product Ba as a marker for transplant-associated thrombotic...

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.

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.

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.

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.