Association of measles virus with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis; while the cause is unknown, it has been speculated that an infectious agent could be the trigger for the disease. Numerous attempts at isolating an agent have been unsuccessful. Our purpose was to identify a virus from diseased tissue from a patient with RA. METHODS: Diseased tissue taken at the time of knee replacement surgery from a patient with RA was inoculated into several cell lines and observed for cytopathic effect. Cells from the tissue were also grown as explants and were examined for viruses. Synovial fluid drawn 4 years prior to the surgery and frozen at -70 degrees C was also inoculated into cell lines. Following the development of a cytopathic effect and identification of the agent, sera from 50 patients with rheumatoid factor (RF)-negative RA were examined for IgM antibodies to the agent. RESULTS: After many inoculations and numerous subpassages, measles virus was identified in 6 cell lines inoculated with either the minced tissue or synovial fluid. Six cell lines co-cultivated with one or more of 9 explants also showed the presence of measles virus. Measles virus was confirmed by immunofluorescence and by neutralization. Eleven of 50 (22%) sera samples from patients with RF-negative RA had IgM antibodies to measles virus recombinant nucleoprotein. CONCLUSION: There is an association between measles virus and RA.

Autoantibodies to tumor necrosis factor in patients with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To detect autoantibodies to tumor necrosis factor (TNF) in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and to determine their clinical correlates. METHODS: Ninety-two patients with RA and 62 with SLE were studied. Sera were examined for autoantibodies to TNF by enzyme linked immunoassay. Levels of these autoantibodies were analyzed in respect to markers of inflammation such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and joint erosions, as well as other clinical, laboratory, and therapeutic aspects of RA and SLE. RESULTS: Anti-TNF levels were higher in those RA patients without erosions, but did not correlate with ESR or CRP. CONCLUSION: These observations suggest that autoantibody anti-TNF may be part of the innate immune system and may contribute to decreased inflammation in patients with RA.

C-reactive protein, anti-C-reactive protein antibodies and clinical atherosclerosis.

There has been considerable interest in the relationship between C-reactive protein (CRP) and atherosclerosis. We have previously demonstrated that individuals, especially those with rheumatoid arthritis and systemic lupus erythematosus, may produce antibodies to CRP. This study was therefore undertaken to determine the possible association between anti-CRP antibodies and atherosclerosis. A total of 103 individuals were identified with or without atherosclerosis, and without clinical rheumatic diseases. They were evaluated with respect to cholesterol, HDL, LDL, high-sensitivity (hs)CRP, and anti-CRP antibody levels, as well as use of statin medications. Individuals with atherosclerosis were much more likely to be taking a statin, and thus have lower lipid levels. However, there was no association between hsCRP or anti-CRP antibody levels with atherosclerosis, statin use, or each other. These observations suggest that anti-CRP antibody is not involved in atherosclerosis, and may represent an epiphenomenon.

Antibody to serum amyloid A.

INTRODUCTION: Serum amyloid A (SAA) is elevated in inflammatory states. While antibodies to CRP, the other major acute phase reactant, have been described, to our knowledge, antibodies to SAA have not. This study was therefore undertaken to determine whether antibodies to SAA could be detected in patients and whether these antibodies are associated with any disease, in particular inflammatory states, using CRP as a proxy for inflammation. METHOD: An ELISA technique was developed for the detection of antibodies to SAA. Specificity was demonstrated by inhibition. Serum from one hundred and thirty-eight patients sent to the Clinical Immunology Laboratory for CRP evaluations were tested for anti-SAA activity. Their charts were reviewed for clinical parameters, in particular for inflammation, to determine association. Patients were also divided into those with normal and elevated levels of CRP, as a proxy for inflammation. As a control we also studied 62 normals. RESULTS: The mean OD and 3 SD of the 62 normal blood bank donors for anti-SAA was 0.411 +/- 0.577. Thus for the purposes of this study 0.988 was determined as the cutoff between normality and abnormality. Sixty-one normals and 114 patients had "normal" levels. Elevated levels were observed in 24 patients and 1 normal. There was an association between elevated levels and aortic stenosis, deep vein thrombosis, and systemic lupus erythematosus, seizures, stroke, and atrial fibrillation. There was no association between anti-SAA levels and CRP levels. CONCLUSIONS: These results show that antibodies to SAA develop in some patients. There was some association with inflammatory cardiovascular diseases.