Detection of apoptosis‐specific autoantibodies directed against granzyme B‐induced cleavage fragments of the SS‐B (La) autoantigen in sera from patients with primary Sjögren's syndrome

• Published in: Clinical and experimental immunology Vol. 142; no. 1; pp. 148 - 154
• Main Authors: Huang, M., Ida, H., Kamachi, M., Iwanaga, N., Izumi, Y., Tanaka, F., Aratake, K., Arima, K., Tamai, M., Hida, A., Nakamura, H., Origuchi, T., Kawakami, A., Ogawa, N., Sugai, S., Utz, P. J., Eguchi, K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.10.2005; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Aged; apoptosis; Apoptosis - immunology; Autoantibodies - blood; Autoantibodies - immunology; autoantibody; Autoantigens - immunology; B-Lymphocytes - immunology; Biological and medical sciences; Cell Line; Cell-Free System - immunology; Cytotoxicity, Immunologic - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; granzyme B; Granzymes; Humans; Immunopathology; La (SS–B); Lupus Erythematosus, Systemic - immunology; Lymphoma - immunology; Male; malignant lymphoma; Medical sciences; Middle Aged; Original; Ribonucleoproteins - immunology; Serine Endopeptidases - immunology; Sjogren's Syndrome - immunology; Sjögren's syndrome; SS-B Antigen; Autoimmunity; Autoimmune disease; Fragmentation; Immunology; Granzyme B; La (SS-B); Lymphoproliferative syndrome; Systemic disease; Primary; Cleavage; Malignant lymphoma; Serum; Diagnosis; Human; Immunopathology; Serine endopeptidases; Enzyme; Stomatology; Antibody; Extractable nuclear antigen; Autoantibody; Malignant hemopathy; Sjögren syndrome; Peptidases; Eye disease; Autoantigen; Cell death; Sjögren's syndrome; Hydrolases; Apoptosis
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2005.02888.x

Summary The objective of this study was to detect autoantibodies against granzyme B cleavage products in sera from patients with primary Sjögren's syndrome (SS). Cell lysates derived from human salivary gland (HSG) cell lines were incubated with granzyme B. The susceptibility to the generation of cleavage fragments of SS autoantigens was assayed by immunoblotting using sera from 57 primary SS patients, 17 primary SS patients with malignant lymphoma (ML), 28 systemic lupus erythematosus (SLE) patients, and 20 healthy controls. A 27 kD protein was recognized by serum autoantibodies in 8 (14·0%) of 57 primary SS patients, 5 (29·4%) of 17 SS patients with ML, 2 (7·1%) of 28 SLE patients, but not in 20 normal subjects. This protein was recognized by anti‐SSB (La) monoclonal antibodies. Granzyme B‐treated recombinant La protein was also shown to migrate as a discrete 27 kD protein by SDS PAGE. Blocking studies demonstrated the existence of an apoptosis‐specific B cell epitope present in sera from 2 of 8 primary SS patients and in 2 of 5 primary SS patients with ML which recognized the 27 kD protein. Granzyme B‐induced La fragments are generated during cytotoxicity in vitro. This is the first report describing autoantibodies in sera from primary SS patients that specifically recognize fragments of the La protein that are produced by the granzyme B protease.