Autoantibodies in Sjögren's syndrome (SS) were identified by their precipitin reactions with tissue antigens in immunodiffusion. The source of antigens was a sonicated extract of human lymphoid cells (WiI2) grown in tissue culture. Three distinct precipitin systems were identified and referred to as precipitins SS‐A and SS‐B, and rheumatoid arthritis precipitin. These studies show that precipitins SS‐A and SS‐B are present in high frequency in sera of patients with SS without associated rheumatoid arthritis (RA) and are absent or present in low frequency in many other connective tissue diseases. On the other hand patients with SS who also had clinical features compatible with RA (SS‐RA) did not have precipitins SS‐A and SS‐B but had rheumatoid arthritis precipitin (RAP). The latter precipitin was also present in RA patients in a similar order of frequency as in SS‐RA. All three precipitin systems were shown to be reactions between immunoglobulins and cellular antigens. The origin of SS‐A and SS‐B antigens was demonstrated by immunofluorescence to be primarily from the nucleus but the origin of RAP in the cell has not been established.
Six autoimmune murine models (MRLh, MRL/n, NZB, NZB/NZW, PN, C57BL/6J-lpr/lpr) were compared with normal control C57BL/6J and DBM2 mice to determine if spontaneous autoimmune disease was associated with evidence of Sjogren's syndrome. Schirmer tests documented dry eyes in NZB/NZW and PN mice; other autoimmune strains and controls had normal tear formation. All autoimmune mice had conjunctivitis, but this abnormality was most severe in the PN strain. Ninety-eight percent of MRL/I and MRL/n mice had mononuclear cell infiltrates in lacrimal glands, and salivary glands were involved to a lesser degree. New Zealand mice and PN mice had smaller gland lesions. The extensive gland destruction in MRL/I and MRLln mice suggested that these substrains merit further studies as animal models of Sjogren's syndrome.
_ _ _ _From the Veterans Administration Medical Center, Columbia, Missouri and the University of MissouriXolumbia.
Symptomatology and objective findings of Sjögren's syndrome were evaluated in 38 consecutive patients with primary biliary cirrhosis. Symptoms of Sjögren's syndrome were present in 18 (47.4%) patients, but were severe enough to warrant therapy in only four (10.5%). Nineteen patients consented to evaluation for Sjögren's syndrome, which included Schirmer's I test, measurement of parotid flow rate and serum autoantibodies, labial minor salivary gland biopsy and human leukocyte antigen typing. Histological changes diagnostic of Sjögren's syndrome were present in five patients (26.3%). All five patients had symptoms of Sjögren's syndrome and three had abnormal Schirmer's I tests, but none had corneal ulcerations or decreased parotid flow rates. Results of serological tests and human leukocyte antigen typing were not similar to those described in patients with primary Sjögren's syndrome but were similar to those described in patients with rheumatoid arthritis and Sjögren's syndrome. These findings indicate that Sjögren's syndrome associated with primary biliary cirrhosis is a form of secondary Sjögren's syndrome resembling that associated with rheumatoid arthritis.
A B S T R A C T The frequencies and levels of antibodies to Epstein-Barr virus (EBV)-specific antigens were determined in paired sera and synovial fluids from patients with rheumatoid arthritis (RA) and in sera from patients with other connective tissue diseases; i.e., systemic lupus erythematosus, progressive systemic sclerosis, and osteoarthritis (OA). The specimens were also tested for the presence of antibodies to RA-associated nuclear antigen. Compared to healthy controls, the patients' sera showed increased frequencies of elevated antibody titers (-320) to Epstein-Barr viral capsid antigen, a correspondingly enhanced (twofold to threefold) geometric mean titer, and an increased frequency of antibodies at elevated titers (-10), usually to the restricted component and rarely the diffuse component of the early antigen complex. Levels ofantibody to the EBV-associated nuclear antigen were within the normal range. Enhancement of antibody titers was more pronounced in seropositive BA patients (i.e., positive for rheumatoid factor) than in those who were not. Enhancement was also found in systemic lupus erythematosus and progressive systemic sclerosis. Antibody to RA-associated nuclear antigen was detected at an increased frequency only in the group of seropositive RA patients (90%), as compared to 8-15% in the other connective tissue diseases and 6-8% in healthy controls. The antibody titers in the synovial fluids equaled or were at most twofold higher or lower than those in the sera. In addition, levels of Portions of this work were published as abstracts in 1979. Arthritis Rheum. 22: 587 and 22: 588. Send reprint requests to
Sera from approximately two-thirds of patients with rheumatoid arthritis contain an antibody which is reactive with a nuclear antigen present in human B-lymphocyte tissue culture cells. The immunological reaction can be demonstrated by precipitation and immunofluorescence. Evidence is present that the reactive nuclear antigen is associated with Epstein-Barr (EB) virus-transformed lymphocytes. Normal human peripheral blood lymphocytes did not contain the nuclear antigen reactive with rheumatoid arthritis sera, but after infection with EB virus, they showed increasing amounts of reactive nuclear antigen as the cells were transformed into continuous lines. Several established human and simian lymphocyte cell lines known to carry EB viral genomes were shown to contain rheumatoid arthritis-associated nuclear antigen. Evidence is presented which suggests that the rheumatoid arthritis-associated nuclear antigen is different from the previously described EB nuclear antigen.
The Ouchterlony technique of double immunodiffusion, combined with some physicochemical characterization of the antigens involved, has been used to characterize several antigen‐antibody systems of importance in certain connective tissue diseases, notably systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjögren's syndrome, rheumatoid arthritis, scleroderma, and poly‐ and dermatomyositis (1–12). These systems appear to have not only considerable diagnostic significance but also importance in determining prognosis and disease course.
Randomly selected sera from 88 patients with systemic lupus erythematosus (SLE) were studied for the frequency of antibodies to SS-A, SS-B, RANA, RNP, Sm, Sc-1, and dsDNA. Results were in agreement with previous reports except for an increased incidence of anti-SS-A antibody (33%). Nine of 14 patients with anti-SS-A antibody on whom serial studies were performed had fluctuating titers. Titer changes often correlated with disease activity and dsDNA antibody levels.
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