Allogeneic B cell response to H-Y minor histocompatibility antigens after donor lymphocyte infusion correlates with disease response

Abstract

Abstract Donor lymphocyte infusion (DLI) can induce remission in many patients who relapse after allogeneic hematopoietic stem cell transplantation (HSCT). We have previously demonstrated that male HSCT patients with female donors frequently develop high-titer antibody responses to H-Y antigens that correlate with disease remission. DLI administered 6 months after T cell depleted HSCT results in a five-fold increase in peripheral B cell numbers. We sought to determine whether allogeneic B cell responses develop after DLI. We expressed 5 recombinant H-Y proteins (DBY, UTY, ZFY, RPS4Y and EIF1AY) and developed sensitive ELISA to quantify the development of specific anti-HY antibodies. First, we studied prophylactic DLI. Twenty-six patients who received T cell depleted HSCT followed 5–7 months later by prophylactic CD8 depleted DLI were tested for H-Y antibodies pre-DLI and 6–12 months after DLI. No H-Y antibodies were detected in any of the pre-DLI serum samples. However, all 6 male HSCT patients with female donors (F→M HSCT) developed high-titer antibodies against at least one H-Y antigen after DLI. In contrast, only 1/20 of the other donor/recipient gender combinations (4 M→M, 8 F→F, 8 M→F) resulted in H-Y antibody (p H-Y Antibody Results in Male Patients with Female Donors Any H-Y Antibody 2 or more H-Y Antibodies TCD HSCT + prophylactic CD8 depleted DLI 6/6 (100%) 4/6 (67%) TCD HSCT alone 3/9 (33%) 1/9 (11%) CD8 depleted DLI for relapse 9/12 (75%) 9/12 (75%) Unmanipulated DLI for relapse 8/12 (67%) 2/12 (17%)