Incidence and epitope specificity of HLA DQA1 and DQB1 antibodies in renal transplant recipients Antonina Piazza1, Giuseppina Ozzella1, Elvira Poggi1, Daniela Caputo2, Rosa Cremona2, Valentina Imbroglini2, Domenico Adorno1 1C.N.R. - Istituto per i Trapianti d'Organo, Rome, Italy, 2Centro Regionale Trapianti - Lazio, Rome, Italy Since epitopes of HLA molecules represent the binding site of alloantibodies, the exact characterization of HLA antibodies has an important for the management of sensitized renal transplant candidates. The recent development of assays using Single Antigen beads coated with DQ heterodimers (DQA1 and DQB1) permit to distinguish DQA1 from DQB1 alloantibodies. Besides, analyzing the beads' reaction patterns in relation to amino acid sequences of antibody-reactive alleles it is possible to identify DQA1 and DQB1 sensitizing epitopes. In 173 renal transplant candidates showing production of HLA class II antibodies we characterized anti-DQ antibodies using HLA class II Single Antigen beads containing 12 DQA1 and 14 DQB1 alleles variously combined each other. One hundred and four (60%) of the HLA class II positive patients produced anti-DQ antibodies; 88 of the 104 recipients had had a previous transplant. Sixty-eight patients had only anti-DQB1 antibodies, 2 had only anti-DQA1 and the remaining 34 had both anti-DQB1 and anti-DQA1. Anti-DQ positive patients were typed for DQA1 and DQB1 alleles by PCR-SSP technique. Correlating the reaction pattern of each antibody to the amino acid sequences of DQA1/DQB1 alleles, we could identify 9 epitopes characteristic of DQA1 molecules and 14 epitopes characteristic of DQB1. Seven (30%) of these 23 epitopes had not been reported yet; 6 were DQA1-epitopes (41K/130A = DQA1*0103; 160D = DQA1*0302, 0303; 75S/107I/161E/163S/175K = DQA1*05; 50L = DQA1*02, 03; 69T = DQA1*04, 06; 75I = DQA1*01, 02, 03, 04, 06) and one was a DQB1-epitope (87Y = DQB1*05, 0604, 0605, 0607, 0609, . . .). This study, carried out on a large number of HLA-DQA1/DQB1 sensitized patients, confirms the great immunogenicity of mismatched DQ molecules of a renal transplant. Furthermore the characterization of detected HLADQ antibodies allowed us to identify seven unreported epitopes of the DQA1/DQB1 molecules. These findings may be useful in increasing our knowledge of HLA epitope repertoire which can lead to an accurate analysis of high panel reactive antibodies.
Incidence and epitope specificity of HLA DQA1 and DQB1 antibodies in renal transplant recipients.
A PIAZZA;G OZZELLA;E POGGI;
2010
Abstract
Incidence and epitope specificity of HLA DQA1 and DQB1 antibodies in renal transplant recipients Antonina Piazza1, Giuseppina Ozzella1, Elvira Poggi1, Daniela Caputo2, Rosa Cremona2, Valentina Imbroglini2, Domenico Adorno1 1C.N.R. - Istituto per i Trapianti d'Organo, Rome, Italy, 2Centro Regionale Trapianti - Lazio, Rome, Italy Since epitopes of HLA molecules represent the binding site of alloantibodies, the exact characterization of HLA antibodies has an important for the management of sensitized renal transplant candidates. The recent development of assays using Single Antigen beads coated with DQ heterodimers (DQA1 and DQB1) permit to distinguish DQA1 from DQB1 alloantibodies. Besides, analyzing the beads' reaction patterns in relation to amino acid sequences of antibody-reactive alleles it is possible to identify DQA1 and DQB1 sensitizing epitopes. In 173 renal transplant candidates showing production of HLA class II antibodies we characterized anti-DQ antibodies using HLA class II Single Antigen beads containing 12 DQA1 and 14 DQB1 alleles variously combined each other. One hundred and four (60%) of the HLA class II positive patients produced anti-DQ antibodies; 88 of the 104 recipients had had a previous transplant. Sixty-eight patients had only anti-DQB1 antibodies, 2 had only anti-DQA1 and the remaining 34 had both anti-DQB1 and anti-DQA1. Anti-DQ positive patients were typed for DQA1 and DQB1 alleles by PCR-SSP technique. Correlating the reaction pattern of each antibody to the amino acid sequences of DQA1/DQB1 alleles, we could identify 9 epitopes characteristic of DQA1 molecules and 14 epitopes characteristic of DQB1. Seven (30%) of these 23 epitopes had not been reported yet; 6 were DQA1-epitopes (41K/130A = DQA1*0103; 160D = DQA1*0302, 0303; 75S/107I/161E/163S/175K = DQA1*05; 50L = DQA1*02, 03; 69T = DQA1*04, 06; 75I = DQA1*01, 02, 03, 04, 06) and one was a DQB1-epitope (87Y = DQB1*05, 0604, 0605, 0607, 0609, . . .). This study, carried out on a large number of HLA-DQA1/DQB1 sensitized patients, confirms the great immunogenicity of mismatched DQ molecules of a renal transplant. Furthermore the characterization of detected HLADQ antibodies allowed us to identify seven unreported epitopes of the DQA1/DQB1 molecules. These findings may be useful in increasing our knowledge of HLA epitope repertoire which can lead to an accurate analysis of high panel reactive antibodies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
