Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission - PubMed (original) (raw)

. 2005 Apr 1;105(7):2973-8.

doi: 10.1182/blood-2004-09-3660. Epub 2004 Dec 21.

Haesook T Kim, Katherine H Miller, Luxuan Guo, Emmanuel Zorn, Stephanie J Lee, Ephraim P Hochberg, Catherine J Wu, Edwin P Alyea, Corey Cutler, Vincent Ho, Robert J Soiffer, Joseph H Antin, Jerome Ritz

Affiliations

Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission

David B Miklos et al. Blood. 2005.

Abstract

Minor histocompatibility antigens (mHAs) are known targets of donor T cells after allogeneic hematopoietic stem cell transplantation (HSCT). In contrast, B-cell responses to mHAs have not been extensively characterized and the clinical significance of antibodies to mHAs is unknown. We tested 121 patients who underwent HSCT and 134 healthy donors for immunoglobulin G (IgG) antibodies against 5 mHAs encoded by genes on the Y chromosome (DBY, UTY, ZFY, RPS4Y, and EIF1AY). Antibodies to at least one H-Y protein developed in 52% of male patients with female donors compared with 8.7% of male patients with male donors (P < .0001), and in 41.4% of healthy females compared with 7.8% of healthy males (P < .0001). H-Y antibodies develop 4 to 12 months after transplantation and persist for long periods. The clinical significance of H-Y antibodies was characterized in 75 male patients with hematologic malignancies who received stem cells from female donors (F --> M HSCT). The presence of H-Y antibodies correlated with chronic graft-versus-host disease (GVHD) by univariate (odds ratio [OR] = 15.5; P < .0001) and multivariable logistic regression analysis (OR = 56.5; P < .0001). Antibody response to Y-chromosome encoded histocompatibility antigens (H-Y antigens) was also associated with maintenance of disease remission (P < .0001). B cells may provide a new target for immune intervention in chronic GVHD.

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Figures

Figure 1.

Figure 1.

Quantitation of IgG antibodies specific for H-Y and H-X proteins. This heatmap depicts IgG ELISA results for 39 sex-mismatched patients (A) and 29 healthy females (B) who developed antibody responses to any H-Y or H-X recombinant protein. Individual samples are represented in rows and each H-Y or H-X protein is represented in a separate column. Negative ELISA results are shown in light blue. The magnitude of positive ELISA results are represented by increasing tones of red. Below each H-Y antigen label, the mean ELISA result for the respective seropositive samples is presented.

Figure 2.

Figure 2.

**Detection of DBY and UTY antibodies after stem cell transplantation.**Sixteen F → M HSCT patients had 5 or more serial plasma samples tested for DBY and UTY antibodies. All had one or more samples test H-Y antibody–negative before later samples tested positive, and 12 had at least 2 negative samples. Eleven patients developed both DBY and UTY antibodies. Four developed only DBY antibody, and one developed only UTY antibody. Smoothing spline curves are superimposed on the scatterplots for anti-DBY and anti-UTY.

Figure 3.

Figure 3.

The cumulative incidence of chronic GVHD and relapse as a function of H-Y antibody response. Cumulative incidence of chronic GVHD (cGVHD) and disease relapse were determined as competing risks for H-Y antibody–positive and –negative patients. Those patients who did not experience chronic GVHD or relapse were censored at the time of last follow-up or death.

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