The predictive value of HY antibodies for chronic graft-versus-host disease

It has been shown that antibodies targeting Y-chromosome encoded proteins (HY antibodies), detected 3 months post-transplant, in male hematopoietic stem cell transplantation (HSCT) recipients, who were transplanted from a female donor (FM), are significantly associated with chronic graft-versus-host disease (cGvHD) development, higher non-relapse mortality (NRM) rates, and poor overall survival (OS).^1,2 In a letter to the editor of Haematologica, published online on 17 January 2019, Jed Paul from Stanford University School of Medicine, Stanford, USA, et al. reported data from a multicenter, retrospective cohort study on HY antibody levels in patients undergoing transplantation to determine the correlation between higher levels of HY antibodies and cGvHD development.³

Patients and methods

• N = 234 patients
• Plasma or serum samples were collected at 3-months and 1-year post-transplant
• Antibodies were quantified against the five most informative HY antigens: DBY, UTY2, ZFY, RPS4Y, and EIF1AY
• Data were collected from clinical trials that used cGvHD development as their study endpoints
• HY antibody seropositivity threshold was set with a control group of n = 60 paired sera and EDTA plasma samples from healthy male blood donors

Key findings

• Patients with antibodies against DBY had a 2.3-fold higher frequency in the 171 cGvHD patients versus the 63 non-cGvHD patients, P = 0.045
• Future cGvHD patients had a higher chance for HY seropositivity, however, this parameter is only predictive for cGvHD development 6–12 months later
• NIH cGvHD severity was available for 79 clinical trial patients
• 3-month DBY seropositivity was significantly predictive for severe cGvHD, P = 0.021
• HY score was established in previous studies: the cumulative number of HY antibody seropositivities for a given sample
• The HY score was found to be the most significant predictor of cGvHD development
• If the HY score is > 1 at 3 months, it was predictive for cGvHD severity, P = 0.039
• A HY score > 2 was found to be a strong predictor of cGvHD development: OR = 3.63, P = 0.027
• Anti-DBY antibodies detected at 3-months correlated with cGvHD development: OR = 2.78, P = 0.053
• N = 185 patients survived the first year after transplantation
  • N = 44 patients never developed cGvHD
  • N = 141 developed cGvHD during this period of time
• 1-year HY score > 1 correlated with a 1.6-fold increase in cGvHD development, P = 0.029

In conclusion, this study evaluating the predictive value of HY antibodies showed that the presence of HY antibodies at 3 months post-transplant predicts cGvHD development. The authors added that “the 3-month HY score has its greatest utility in predicting which patients are more likely to develop severe cGvHD. As such, HY scoring at 3 months could identify patients at high risk for cGvHD prevention trials.”