title: ANCA patients have T cells responsive to complementary PR-3 antigen.
abstract: Some patients with proteinase 3 specific anti-neutrophil cytoplasmic autoantibodies (PR3-ANCA) also have antibodies that react to complementary-PR3 (cPR3), a protein encoded by the antisense RNA of the PR3 gene. To study whether patients with anti-cPR3 antibodies have cPR3-responsive memory T cells we selected conditions that allowed cultivation of memory cells but not naïve cells. About half of the patients were found to have CD4+TH1 memory cells responsive to the cPR3(138-169)-peptide; while only a third of the patients had HI-PR3 protein responsive T cells. A significant number of T cells from patients responded to cPR3(138-169) peptide and to HI-PR3 protein by proliferation and/or secretion of IFN-gamma, compared to healthy controls while there was no response to scrambled peptide. Cells responsive to cPR3(138-169)-peptide were not detected in MPO-ANCA patients suggesting that this response is specific. The HLADRB1(*) 15 allele was significantly overrepresented in our patient group and is predicted to bind cPR3(138-169) peptide with high affinity. Regression analysis showed a significant likelihood that anti-cPR3 antibodies and cPR3-specific T cells coexist in individuals, consistent with an immunological history of encounter with a PR3-complementary protein. We suggest that the presence of cells reacting to potential complementary protein pairs might provide an alternative mechanism for auto-immune diseases.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Jiajin
authors.initials: J
authors.lastname: Yang
authors.forename: David J
authors.initials: DJ
authors.lastname: Bautz
authors.forename: Sofia
authors.initials: S
authors.lastname: Lionaki
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hogan
authors.forename: Hyunsook
authors.initials: H
authors.lastname: Chin
authors.forename: Roland M
authors.initials: RM
authors.lastname: Tisch
authors.forename: John L
authors.initials: JL
authors.lastname: Schmitz
authors.forename: Barrak M
authors.initials: BM
authors.lastname: Pressler
authors.forename: J Charles
authors.initials: JC
authors.lastname: Jennette
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Falk
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Preston
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D010446:Peptide Fragments; C534210:complementary PR3 (138-169), human; D053146:Myeloblastin