A confirmation of chronic graft-versus-host disease prediction using allogeneic HY antibodies following sex-mismatched hematopoietic cell transplantation

Abstract

Chronic graft-versus-host disease (cGvHD) limits the effectiveness of hematopoietic cell transplantation (HCT) and often leads to significant morbidity and non-relapse mortality. 1 We have previously shown that antibodies targeting Y-chromosome encoded proteins (HY antibodies) detected at 3-months post transplant in male HCT patients who receive grafts from a female donor (F→M) are associated with cGvHD development, non-relapse mortality (NRM), and decreased overall survival (OS). 2,3 However, it is not known if this marker can be applied to the general population. In this multi-center, retrospective cohort study, we measured HY antibody levels in 234 F→M HCT patients with either plasma or serum samples collected at both the 3-month and 1-year post-transplant time points and determined the multivariable-adjusted relationship between the presence of multiple HY antibodies (represented as HY score) and cGvHD development.We quantified antibodies against the five most informhaematologica 2019; 104:e314 LETTERS TO THE EDITOR Figure 1. Anti-HY antibody responses in female donor to male recipient (F→M) hematopoietic cell transplantation (HCT) recipients with and without chronic graft-versus-host disease (cGvHD). Comparison included 234 F→M samples taken three months post transplant (3M) and 185 samples taken one year post transplant (1Y). Intensity of the antibody response is color-coded as a multiple of each HY-seropositivity threshold. HY score represents the cumulative number of seropositive HY antigens. Seropositivity frequencies for each antibody are listed along the bottom border of each heat map. HY score frequency refers to the frequency of an HY score >1.

Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

“…Chronic GVHD is an autoimmune-like syndrome caused by the interactions of donor CD4 + T and B cells and production of IgG (7)(8)(9)(10)(11). Recently, antibodies have been reported to play an important role in the development of cGVHD (12)(13)(14)(15)(16)(17)(18)(19). Previous studies showed that donor B cellderived antibodies augmented the development of bronchiolitis obliterans and perpetuated cutaneous cGVHD in mice (7,9).…”

BM is preferred over PBSCs in transplantation from an HLA-matched related female donor to a male recipient

“…[3][4][5][6][7][8][9][10] Biologically, naïve female-donor T or B cells are considered to recognize HY proteins as alloantigens and attack tissues of male recipients, eventually leading to cGVHD development or deterioration. 7,[11][12][13][14][15][16] In fact, HY Abs were detected in half of male recipients with female donors 3 months after HCT, and the cumulative number of HY Abs 3 months after HCT predicts subsequent cGVHD development. In addition, an increased cumulative number of HY Abs 3 months after HCT was associated with the severity of cGVHD and NRM.…”

“…[3][4][5][6][7][8][9][10] This adverse effect of FtoM HCT is thought to result from an allogeneic immune response against minor histocompatibility antigens encoded on the Y chromosome of the male recipient (HY antigens). 7,[11][12][13][14][15][16] In fact, the cumulative number of anti-HY antigen antibodies (HY Abs) was shown to be significantly associated with increased risks of chronic GVHD and nonrelapse mortality (NRM). 14 In contrast, advances regarding cell sources such as peripheral blood stem cells (PBSCs) mobilized by granulocyte-colony stimulating factor have contributed to the worldwide adoption of HCT.…”

Non-HLA Abs in Solid Organ Transplantation

“…These minor antigens have been widely studied in hematopoietic stem cell transplantation. In this setting, antibodies directed against them have been associated with increased rates of graft versus host disease, as well as lower levels of relapse in male recipients/female donor pairs [92,93]. In solid organ transplantation, the impact of H-Y antigens has not been as extensively described.…”