Affiliation:
1. *Laboratoire d’Immunologie et Histocompatibilité, Hôpital Saint Louis, Paris, France
2. †INSERM UMRS 976, Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
3. ‡INSERM UMRS 1016, CNRS 8104, Institut Cochin, Paris, France
4. §Department of Medical Genetics, University of Tsukuba, Ibaraki, Japan
5. ¶Laboratoire d’Immunologie et d’Histocompatibilité, CHU de Caen, Caen, France
6. ǁDepartment of Research and Development, One Lambda, West Hills, CA
Abstract
Abstract
In transplantation, anti-HLA Abs, especially targeting the DQ locus, are well-known to lead to rejection. These Abs identified by Luminex single Ag assays recognize polymorphic amino acids on HLA, named eplets. The HLA Eplet Registry included 83 DQ eplets, mainly deduced from amino acid sequence alignments, among which 66 have not been experimentally verified. Because eplet mismatch load may improve organ allocation and transplant outcomes, it is imperative to confirm the genuine reactivity of eplets to validate this approach. Our study aimed to confirm 29 nonverified eplets, using adsorption of eplet-positive patients’ sera on human spleen mononuclear cells and on transfected murine cell clones expressing a unique DQα- and DQβ-chain combination. In addition, we compared the positive beads patterns obtained in the two commercially available Luminex single Ag assays. Among the 29 nonverified DQ eplets studied, 24 were confirmed by this strategy, including the 7 DQα eplets 40E, 40ERV, 75I, 76 V, 129H, 129QS, and 130A and the 17 DQβ eplets 3P, 23L, 45G, 56L, 57 V, 66DR, 66ER, 67VG, 70GT, 74EL, 86A, 87F, 125G, 130R, 135D, 167R, and 185I. However, adsorption results did not allow us to conclude for the five eplets 66IT, 75S, 160D, 175E, and 185T.
Funder
Agence Nationale de la Recherche
Programme hospitalier de recherche clinique
Fondation pour la Recherche Médicale
Publisher
The American Association of Immunologists