Incidence and specificity of HLA antibodies in multitransfused patients with acquired aplastic anemia.
BACKGROUND
This study aimed to establish the prevalence and characteristics of anti-HLA in antibody acquired aplastic anemia patients following cessation of antithymocyte globulin therapy and to characterize antibody in terms of epitope specificity.


METHODS
One hundred and fifty multitransfused, untransplanted patients from eight European centers were investigated by serologic methods.


RESULTS
Sixty-two percent were antibody positive. Eighteen HLA-Class-I-specific antibodies (15 IgG, 3 IgM) were identified in 13 patients; 13 antibodies were specific for HLA-A epitopes and 5 for HLA-B. Epitope analysis identified significant correlation between serum reactivity and amino acid substitutions associated with HLA-Class-I epitopes. An excess of antibodies to HLA-A1-associated cross-reactive groups was identified. There was no significant difference in antibody frequency in patients taking cyclosporine compared to those who were not.


CONCLUSIONS
Data suggested a contribution from B cell memory of alloantigens introduced during pregnancy. In some cases, antibody production continued many years after the last transfusion, and although the target varied between individual patients, the antibody to HLA was focused on a few specific Class I epitopes, the majority of which mapped to the HLA-A molecule.
Laundy
G J
GJ
University of Bristol, Transplantation Sciences, and Departmentof Immunology and Immunogenetics, Southmead Hospital, Bristol, United Kingdom. godfrey.laundry@bristol.ac.uk
Bradley
B A
BA
Rees
B M
BM
Younie
M
M
Hows
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology* / Q000628:therapy; D000918:Antibody Specificity; D000961:Antilymphocyte Serum; D003430:Cross-Sectional Studies; D005060:Europe; D005260:Female; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017713:Platelet Transfusion; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000276:immunology / Q000628:therapy; D015995:Prevalence; D011897:Random Allocation; D013601:T-Lymphocytes; D065227:Transfusion Reaction
D000961:Antilymphocyte Serum; D006680:HLA Antigens; D006681:HLA-D Antigens; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies