An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of antinuclear antibodies (ANAs) previously established as diagnostic and/or prognostic marker ANAs for various connective tissue diseases. The antigen used in ELISA is a mixture of purified recombinant or natural antigens including single-and double-stranded DNA, RNP, Sm, SS-A/Ro, SS-B/La, centromere, topoisomerase I and Jo-1 antigens. Thirty hundred and fifty nine patients sera from a variety of connective tissue diseases and 113 normal human sera (NHS) were examined.
ELISA ANAs were positive in 3.5% of NHS and 80.2% of patients sera at cut off index 11.5, whereas indirect immnofluorescent antinuclear antibodies (FANAs) using HEp-2 cells were positive in 9.7% of NHS and 92.5% of patients sera at 1:160 serum dilution. More than 80% of sera from systemic lupus erythematosus, mixed connective tissue disease and primary Sjögren's disease were ELISA ANAs positive. Mean value of ELISA ANAs was highest in sera of patients with MCTD.
ELISA ANAs were positive in 92.5% of sera with marker ANAs for connective tissue diseases. Mean value of ELISA ANAs was higher in sera with more than two marker ANAs than in sera with a single ANA or in sera without marker ANAs. In contrast incidence and mean value of ELISA ANAs were low in sera positive for anti topoisomerase I antibody or anti Jo-1 antibody. Sensitivity, specificity and agreement (accuracy) for connective tissue diseases with marker ANAs were as follows: ELISA ANAs (at index 11.5): 92.5%, 88.3% and 90.9%: FANAs (at 1:160 serum dilution): 99.0%, 70.4% and 88.1%, respectively.
ELISA ANAs, thus, are specific for connective tissue diseases when compared to FANAs and previous ELISA for the detection of total ANAs. Moreover, ELISA ANAs are able to measure precise ANAs titers and are much less labor intensive when screening a large number of clinical specimens.

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Of 49 patients with chronic hepatitis C treated by interferon (IFN), we measured 2'-5'-oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum before and after the IFN therapy and studied the correlation with the clinical outcome. Before IFN therapy, the levels of 2-5 AS in PBMC and serum were significantly higher in patients with chronic hepatitis C than in healthy controls, though there was no correlation between the 2-5 AS activity and the clinical outcome. When PBMC were stimulated with IFN in vitro, the induced 2-5 AS activities in patients with chronic hepatitis C were almost same as those in healthy controls. Among patients infected with hepatitis C virus (HCV) genotype II which was considered relatively resistent to IFN, patients whose HCV was disappeared from serum by IFN therapy showed good induction of 2-5 AS activity by IFN in vitro, whereas patients in which serum HCV remained positive after the therapy showed poor response to IFN in vitro. The levels of 2-5 AS in PBMC 2 months after IFN therapy were still higher in patients whose HCV was continuously disappeared from serum by the therapy (complete remission) than in healthy controls. The in vitro induction of 2-5 AS in patients whose HCV in serum remained positive after the therapy was significantly lower than in patients with complete remission. The induction of 2-5 AS activity in patients to whom IFN therapy was ineffective, significantly decreased after the IFN therapy as compared with the activity measured before the therapy.
Thes findings suggest that measurement of 2-5 AS activity in PBMC in vitro through IFN therapy might be useful for predicting in vivo responsibility to IFN and also knowing the change of the responsibility.

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We report a case of congenital complete heart block (CCHB). A 38-year-old woman was admitted our hospital because of fetal bradycardia at 21 weeks 3 days of gestational age. She had no symptom of collagen disease. On admission, laboratory data showed positive anti-nuclear antibodies, anti-SS-A/Ro antibodies and anti-52kD SS-A/Ro antibodies. But anti-60kD SS-A/Ro and anti-SS-B/La antibodies were negative. Consequently anti-52kD SS-A/Ro antibodies positive woman had an infant with CCHB. The baby was equipped with pacemaker at the age of 2 months. This report suggests that anti-52kD SS-A/Ro antibodies may play an important role in the development of CCHB.

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A 64-year-old female referred to our hospital because of severe anemia. Peripheral blood examination showed macrocytic anemia; red blood cell count was 1.49×10⁶/μl, hemoglobin concentration was 5.6 g/dl, hematocrit was 16.1% and MCV was 108 fl. Serum VB 12 level was significantly low as 58 pg/ml. Upper gastrointestinal examination disclosed chronic atrophic gastritis. Anti-intrinsic factor and anti-parietal cell antibodies were detected in the serum and Schilling's test was positive. Thus a diagnosis of pernicious anemia was made. Though the serum free T 3 and free T 4 levels were in normal ranges, the eleveted serum TSH and positive tests for anti-microsome and anti-thyroglobulin antibodies indicated that the patient had chronic thyroiditis. Then other endocrinological examinations were performed. Low level of urinary 17-OHCS and a hypo-reactive pattern of rapid ACTH test led to a diagnosis of latent adrenal insufficiency. This case could be categorized into polyglandular autoimmune syndrome.

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In April 1988, a 23 year-old woman developed high fever, arthralgia, eruptions and splenomegaly. She was treated with non Steroid anti-inflamatory drugs, and the symptoms disappeared. In June 1991, she was diagnosed as adult Still's disease and treated with prednisolone. In July 1994, she was treated with pulse therapy methylprednisolone due to high fever, eruptions, arthralgia and the high levels of ferritin. However, due to the marked increase of serum transaminase and bilirubin levels, she was reffered to University hospital. She developed hepatic failure after admission Bone-marrow puncture revealed hemophagocytosis. She died ten days after admission. She was diagnosed as hemophagocytic syndrome combiend with acute hepatic failure.

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A 25-year-old woman was admitted for general arthralgia in July, 1989. Reactive arthritis with arthralgia after Shigellosis was diagnosed by sex, localization of arthralgia and positive for HLA-B 27. Within 3 weeks after starting diclifenac sodium 75mg/day, the arthralgia remitted. It has been reported that patients who are positive for HLA-B 27 have a more severe acute or chronic sacroiliitis, and our case may support this report.

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We describe a 58-year-old woman who developed Wegener's granulomatosis (WG) complicated by a perforation of the transverse colon caused by necrotizing granulomatous vasculitis. In addition, her colon lesion continued in spite of high dose corticosteroid and cyclophosphamide therapy. She was admitted to our hospital because of her severe tonsillitis in Dec., 1994. She was diagonosed as having WG because she had oral ulcer, antibioticsresistant lung infiltration, renal dysfunction and positive C-ANCA. Just after we started high dose steroid therapy, the transverse colon was perforated because of vasculitis, and she underwent emergency operation. Many vasculitic lesions were found in the small intestine, colon, and mesenterium. The disease was improved by corticosteroid and cyclophosphamide therapy except for a sustained ulcer with necrotizing vasculitis in the sigmoid colon region even 1 year after the operation. Although WG rarely complicates digestive tract lesions as initial manifestations, they reach 12% of the causes of death of WG in Japan. Therefore, we should take care of digestive tract lesions when we follow-up patients with WG.

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