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.”

  1. Nakasone H. et al. Allogeneic HY antibodies detected 3 months after female-to-male HCT predict chronic GVHD and nonrelapse mortality in humans. Blood. 2015 May 14; 125(20):3193-3201. DOI: 10.1182/blood-2014-11-613323.
  2. Miklos D.B. et al. Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors. Blood. 2004 Jan 1; 103(1):353–359. DOI: 10.1182/blood-2003-03-0984.
  3. Paul J. et al. A confirmation of chronic graft-versus-host disease prediction using allogeneic HY antibodies following sex-mismatched hematopoietic cell transplantation. Haematologica. 2019 Jan 17. DOI: 10.3324/haematol.2018.199646. [Epub ahead of print].
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