Search

Genetics and gut microbiota contribute to the development of autoimmune diseases. SKG mice, which harbor a point mutation in the ZAP70 gene, develop autoimmune arthritis in BALB/c background and systemic lupus erythematosus in C57BL/6 background. Defective TCR signaling by ZAP70 mutation alters thymic selection thresholds and allows the positive selection of otherwise negatively selected self-reactive T cells. On the other hand, defective TCR signaling attenuates the positive selection of certain microbiota-reactive T cells, which lead to impaired IgA synthesis at mucosal site and gut dysbiosis. Gut dysbiosis, in turn, promotes autoimmunity via driving Th17 differentiation. Thus, defective TCR signaling leads to autoimmunity by altering thymic selection thresholds of self-reactive T cells and microbiota-reactive T cells. In this review, genomics-microbiota interactions for the development of autoimmunity will be discussed with the special focus on the recent finding obtained from animal models of autoimmunity with defective TCR signaling.

We made a preclinical study of CA 54/61, a recently developed marker of ovarian tumors, and also conducted a clinical study of it using serum samples collected from 58 institutions located throughout Japan. This paper describes the results of the preclinical study of the CA 54/61 marker that were obtained with a kit based on an enzyme immunoassay (EIA), and also the findings with the kit in the clinical study pertaining to the normal range of its values, its values relative to age, menstrual cycle, and pregnancy, and its correlations with other tumor markers. The tests for reproducibility of assay results, the analytical recovery test, and the dilution test all gave favorable results: the marker proved reliable in both precision and reproducibility. Two cut-off values were used: the mean + 2 S.D. of the mean for healthy subjects, or 20 U/ml; and the value for the maximum diagnostic efficacy, i.e., 12 U/ml. The assay results did not vary greatly with either age, menstrual cycle or pregnancy stage, which suggested that CA 54/61 might be a marker less liable to be affected by physiological conditions prevailing at the time of sample collection. The result correlated poorly with those of assays with other markers; thus CA 54/61 proved to differ in property from the previously recognized tumor markers.