Saline extracts of rabbit thymus were found to contain many nuclear antigens that reacted with antibodies in the sera of patients with systemic rheumatic diseases. Counterimmunoelectrophoresis (CIE) was used to detect antibodies to nuclear acidic protein (Sm), nuclear ribonucleoprotein (RNP), and antibody to nuclear antigen B, which was reported previously in Sjogren's syndrome. All these nuclear antigens behaved as anions with different mobilities in CIE and could be distinguished from one another by the locations of the precipitin lines. They could also be distinguished by the facts that the nuclear RNP precipitin lines were abolished by digestion with ribonuclease whereas others were unaffected, and that Sm precipitin lines developed later than other precipitin lines. With this technique antibody to nuclear RNP was detected in 46% of patients with systemic lupus erythematosus (SLE) compared to 26% detected by the he- this antibody was not detectable in the same group of patients by immunodiffusion. This study shows that CIE is a rapid and sensitive technique for detecting precipitating antibodies to a number of nuclear acidic antigens. Methods are described to identify the immunochemical specificities of the precipitin lines by the use of standard reference sera.

Objective. Methotrexate (MTX) is used as an anchor drug for rheumatoid arthritis (RA). Lymphoproliferative disease (LPD) occasionally develops in patients treated with MTX, and is known as MTX-associated LPD (MTX-LPD).Although MTX-LPD occurs mainly in RA patients, it has not been established if MTX administration is an independent risk factor for LPD in RA patients. We examined the clinical characteristics of MTX-LPD in Japanese RA patients and attempted to determine the risk factors for MTX-LPD development. Methods. We performed a nested case-control study on RA patients. We enrolled 5,753 RA patients from Kagawa, Japan. In age-and sex-matched patients, we separated patients who did not develop LPD under MTX treatment (MTX non-LPD group) from those that did (MTX-LPD group) and conducted a comparative examination. We used multivariate analysis to determine the independent risk factors for MTX-LPD onset. Results. There were 28 patients in the MTX-LPD group and 125 patients in the MTX non-LPD group. Multivariate analysis of the parameters extracted by univariate analysis revealed that the mean MTX dose was a risk factor for MTX-LPD after adjusting for age; therefore, higher MTX dose is associated with LPD onset in RA patients. Conclusion. MTX is an independent risk factor for LPD onset in Japanese RA patients.

Objective-KL-6 is a mucin-like high molecular weight glycoprotein, which is strongly expressed on type II alveolar pneumocytes and bronchiolar epithelial cells. It has been demonstrated that the KL-6 antigen is a useful marker for estimating the activity of interstitial pneumonia. In this study, it is hypothesised that serum KL-6 is a useful marker to evaluate the activity of interstitial pneumonia associated with polymyositis/ dermatomyositis (PM/DM). Methods-KL-6 was measured in sera in 16 patients diagnosed with PM/DM. Five had non-specific interstitial pneumonia (NSIP), three had diVuse alveolar damage (DAD), and eight had no pulmonary involvement, and 10 were normal nonsmokers as a control group. The correlation was also evaluated between the KL-6 level and each clinical course in patients with pulmonary involvement associated with PM/DM. Immunohistochemical analysis using monoclonal anti-KL-6 antibody was also performed. Results-KL-6 concentrations in sera of patients with interstitial pneumonia associated with PM/DM were significantly high compared with those of PM/DM without interstitial pneumonia, and normal non-smokers. KL-6 concentrations in sera in patients with DAD significantly increased compared with those of other groups. KL-6 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical study using pulmonary tissues obtained from patients with DAD demonstrated that the hyaline membrane, proliferating type II pneumocytes, bronchial epithelial cells and some endothelial cells in pulmonary veins were stained by antihuman KL-6 antibody.Conclusion-These data demonstrate that measurement of serum KL-6 was a useful marker to evaluate the activity of acute interstitial pneumonia associated with PM/DM.