title: Novel polymorphisms in HLA-DOA and HLA-DOB in B-cell malignancies.
abstract: In B cells, HLA-DO controls HLA-DM-mediated peptide loading on MHC class II molecules. We analyzed whether HLA-DO mutations are associated with autoimmune diseases characterized by an autoantibody component and with a linkage to HLA-DR or HLA-DQ. These diseases include systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and Graves' disease. In addition, several B-cell leukemias were screened for mutations in HLA-DO. A limited number of polymorphisms in DOA and DOB were found, most of which are non-coding changes or result in a conserved amino acid change. A novel non-conserved Arg to Cys mutation in DOA was found in a patient suffering from chronic lymphocytic leukemia. Further analysis did not reveal any effect on the function of HLA-DO. We conclude that HLA-DO variants are not critically involved in the autoimmune diseases and B-cell leukemias studied here.
authors.affiliation: Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Lith
authors.forename: Marieke
authors.initials: M
authors.lastname: van Ham
authors.forename: Jacques
authors.initials: J
authors.lastname: Neefjes
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D006681:HLA-D Antigens; C046148:HLA-DO antigens