title: Antibodies to HLA-E may account for the non-donor-specific anti-HLA class-Ia antibodies in renal and liver transplant recipients.
abstract: The non-donor-specific anti-HLA-Ia antibodies correlate significantly with lower graft survival in organ transplant patients. Based on our earlier findings that anti-HLA-E murine monoclonal antibodies (MEM-E/02 and 3D12) reacted with different HLA-Ia alleles and the peptides shared by HLA-E and HLA class, Ia alleles inhibited the HLA-Ia reactivity of the anti-HLA-E antibodies in normal non-alloimmunized males, the possibility of that anti-HLA-E IgG may account for the non-donor-specific anti-HLA-Ia antibodies in the allograft recipients was examined by multiplex-Luminex®-immunoassay. About 73% of renal and 53% of liver transplant patients' sera with high level of anti-HLA-E IgG showed reactivity to different non-donor HLA-Ia alleles. About 50% renal and 52% liver allograft recipients' sera with low level of anti-HLA-E IgG had no reactivity to any HLA-Ia alleles; however, the IgG isolated from the same sera with protein-G columns showed the presence of anti-HLA-E IgG with HLA-Ia reactivity. Furthermore, both recombinant HLA-E and the IgG-free serum containing soluble HLA-E (sHLA-E) inhibited HLA-Ia reactivity of anti-HLA-E murine monoclonal IgG significantly. The data suggest that the HLA-Ia reactivity of the anti-HLA-E antibody accounts for the non-donor-specific anti-HLA-Ia antibodies. It is proposed that the sHLA-E heavy chain, shed in circulation after organ transplantation, may expose cryptic epitopes of HLA-E to elicit anti-HLA-E IgG antibodies, which may cross react with HLA-Ia alleles due to the peptide sequences shared between them. This study provides a new explanation for the presence of non-donor-specific antibodies for non-existing HLA-Ia alleles, frequently observed and correlated with survival in organ transplant recipients.
authors.affiliation: Terasaki Foundation Laboratory, 11570 West Olympic Boulevard, Los Angeles, CA 90064, USA. ravimh@terasakilab.org
authors.forename: Mepur H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: Tho
authors.initials: T
authors.lastname: Pham
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ozawa
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000483:Alleles; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015153:Blotting, Western; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D000097625:HLA-E Antigens
chemical_list: D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D000097625:HLA-E Antigens