Data from: Allogeneic H-Y antibodies detected 3 months after female to male sex-mismatched HCT predict chronic GVHD and non-relapse mortality

Allogeneic antibodies against minor histocompatibility antigens encoded on the Y-chromosome (HY-Abs) develop following hematopoietic cell transplant of male recipients with female donors (F→M HCT). However, the temporal association between HY-Ab development and chronic graft-versus-host disease (cGVHD) has yet to be elucidated. We studied 136 adult F→M HCT patients with plasma prospectively collected through 3 years post-transplant and measured IgG against six H-Y antigens (DBY, UTY, ZFY, RPS4Y, EIF1AY, and SMCY). Multiple HY-Abs were frequently detected beginning 3 months post-transplant: 78 (57%) of F→M patients were seropositive for at least one of the six HY-Abs 3 months post-transplant. Three month seropositivity for each HY-Ab was associated with a persistent seropositive response throughout the post-transplant follow-up period (P<0.001 in each). There were no associations between pre-transplant features and 3 month overall HY-Ab development. Detection of multiple HY-Abs at 3 months (represented by HY-score) was significantly associated with an increased risk of cGVHD (HR 1.37, P<0.0001) and non-relapse mortality (HR 1.66, P<0.01). Compared to clinical factors alone, the addition of HY-score and clinical factors improved the predictive potential of cGVHD (P<0.01). Monitoring HY-Ab development thus stratifies cGVHD risk in F→M HCT and may support preemptive prophylaxis therapy for cGVHD beginning 3 months post-transplant.