title: Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera.
abstract: Intravenous immunoglobulin (IVIg) reacted with a wide array of human leucocyte antigen (HLA) alleles, in contrast to normal sera, due possibly to the purification of IgG from the pooled plasma. The reactivity of IgG purified from normal sera was compared with that of native sera to determine whether any serum factors mask the HLA reactivity of anti-HLA IgG and whether IgG purified from sera can recognize the HLA types of the corresponding donors. The purified IgG, unlike native sera, mirrored IVIg reactivity to a wide array of HLA-I/-II alleles, indicating that anti-HLA IgG may be masked in normal sera - either by peptides derived from soluble HLA or by those from antibodies. A < 3 kDa peptide from the complementarity-determining region (CDR) of the Fab region of IgG (but not the HLA peptides) masked HLA recognition by the purified IgG. Most importantly, some of the anti-HLA IgG purified from normal sera - and serum IgG from a few donors - indeed recognized the HLA types of the corresponding donors, confirming the presence of auto-HLA antibodies. Comparison of HLA types with the profile of HLA antibodies showed auto-HLA IgG to the donors' HLA antigens in this order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%) and B (7%). The auto-HLA antibodies, when unmasked in vivo, may perform immunoregulatory functions similar to those of therapeutic preparations of IVIg.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: P I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: C Y
authors.initials: CY
authors.lastname: Maehara
authors.forename: V
authors.initials: V
authors.lastname: Jucaud
authors.forename: S
authors.initials: S
authors.lastname: Kawakita
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.forename: W
authors.initials: W
authors.lastname: Yamashita
mesh_terms: D000483:Alleles; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification; D022801:Complementarity Determining Regions / Q000276:immunology* / Q000302:isolation & purification; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000276:immunology* / Q000302:isolation & purification; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology; D008297:Male
chemical_list: D001323:Autoantibodies; D022801:Complementarity Determining Regions; D006680:HLA Antigens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors
keywords: CDR peptide; HLA autoantibody; HLA reactivity; HLA typing; intravenous immunoglobulin