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1.
PLoS One ; 8(8): e71376, 2013.
Article in English | MEDLINE | ID: mdl-23951151

ABSTRACT

Influenza is a major cause of morbidity and mortality. Despite vaccination, many elderly recipients do not develop a protective antibody response. To determine whether Human Leukocyte Antigen (HLA) alleles modulate seroprotection to influenza, a cohort of HLA class II-typed high-risk vaccine recipients was investigated. Haemagglutinin inhibition (HAI) titres were measured 14-40 days post-subunit vaccination. Seroprotection was defined as HAI titres reaching 40 or greater for all three vaccine strains. HLA-DRB1*04∶01 and HLA-DPB1*04∶01 alleles were detected at higher frequencies in seroprotected compared with non-seroprotected individuals. Thus, the presence of certain HLA class II alleles may determine the magnitude of antibody responses to influenza vaccination.


Subject(s)
Antibodies, Viral/biosynthesis , HLA-DP beta-Chains/genetics , HLA-DRB1 Chains/genetics , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Orthomyxoviridae/immunology , Vaccination , Aged , Aged, 80 and over , Alleles , Antibodies, Viral/blood , Female , Gene Expression , Gene Frequency , HLA-DP beta-Chains/immunology , HLA-DRB1 Chains/immunology , Hemagglutination Inhibition Tests , Humans , Immunity, Active , Influenza Vaccines/administration & dosage , Influenza, Human/blood , Influenza, Human/genetics , Influenza, Human/immunology , Male , Vaccines, Subunit
2.
Hum Immunol ; 72(10): 827-34, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21664940

ABSTRACT

Even when kidney allografts are well matched for human leukocyte antigen (HLA) and anti-HLA antibodies are not detected, graft rejection can still occur. There is evidence that some patients who lose their graft have antibodies specific for major histocompatibility complex (MHC) class I-related chain A (MICA) antigens. We investigated whether mismatching MICA alleles associates with MICA antibody production and graft rejection or dysfunction. MICA and HLA antibody screening in 442 recipients was performed, and specificities were confirmed in a subgroup of 227 recipients using single-antigen multiplex technology. For assignment of MICA antibody specificity, we used three independent assays. In addition, MICA alleles of 227 recipients and donors were determined by DNA sequencing. In all, 17 patients (7.5%) had MICA antibodies, and 13 patients (6%) developed MICA donor-specific antibodies (DSA). Multivariate analysis revealed MICA mismatching, as an independent significant factor associated with the presence of MICA antibodies (p = 0.009), and 14 mismatched MICA residues significantly correlated with MICA antibody production. MICA and HLA antibodies significantly associated with acute rejection (AR) and MICA DSA and HLA DSA correlated with decreased graft function by univariate and multivariate analysis. We conclude that mismatching for MICA epitopes in renal transplantation is a mechanism leading to production of MICA antibodies that associate with AR and graft dysfunction.


Subject(s)
Biomarkers/blood , Graft Rejection/immunology , Graft Survival/immunology , Histocompatibility Antigens Class I/immunology , Isoantibodies , Kidney Transplantation/immunology , Kidney/immunology , Adult , Alleles , Antibody Specificity/genetics , Antibody Specificity/immunology , Epitopes/genetics , Epitopes/immunology , Female , Graft Rejection/blood , Graft Rejection/diagnosis , Histocompatibility Antigens Class I/blood , Histocompatibility Testing , Humans , Isoantibodies/blood , Isoantibodies/genetics , Isoantibodies/immunology , Kidney/pathology , Kidney Transplantation/pathology , Male , Middle Aged , Multivariate Analysis , Risk Factors , Sequence Analysis, DNA , Transplantation, Homologous
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