Poor maternal glycemic control increases maternal and fetal risk for adverse outcomes, and strict management of gestational diabetes mellitus (GDM) is recommended to prevent neonatal and maternal complications. However, risk factors for the requirement of antenatal insulin treatment (AIT) are not well-investigated in the pregnant women with GDM. We enrolled 37 pregnant women with GDM and investigated the risk for AIT by comparing the patients with AIT (AIT group; n = 10) and without insulin therapy (Diet group; n = 27). The 1-h and 2-h plasma glucose levels and the number of abnormal values in 75 g OGTT were significantly higher in AIT group compared with Diet group. By logistic regression analysis, plasma glucose level at 1-h was significant predictor for AIT and the odds ratios were 1.115 (1.004–1.239) using forward selection method and 1.192 (1.006–1.413) using backward elimination method. There were no significant differences in obstetrical outcomes and neonatal complications. 1-h plasma glucose levels in 75 g OGTT are useful parameters in predicting the requirement for AIT in GDM. Both maternal and neonatal complications are comparable in GDM patients with and without insulin therapy.

Background and aims Mizoribine is an inhibitor of inosine monophosphate dehydrogenase, which is widely used for patients with lupus nephritis and also patients after renal transplants. Its anti-cytomegaloviral effect is unique as an immunosuppressant. We examined the efficacy and safety of early sequential combination of mizoribine and tacrolimus in lupus nephritis. Methods Retrospective review of electric medical record was performed for all the 63 patients who received the combination therapy of mizoribine and tacrolimus and corticosteroids for induction or maintenance of lupus nephritis at St. Luke's International Hospital, Tokyo, Japan. For efficacy analysis, we extracted a series of change in serum creatinine, serum complement level, urine protein creatinine ratio, dose of cortico-steroid. We further reviewed safety profile such as adverse events occurred during the use of multi-target therapy, drug survival rate, or reasons for discontinue multi-target therapy in all patients. Complete remission of lupus nephritis was defined as a value of proteinuria <0.5 g/gCr, normal urinary sediment, serum albumin 3.5 g/dl and a normal value of serum creatinine. Results Fifty six out of the sixty three patients (female: male=59:4, average age 37.4 years old) achieved complete remission in 6 months and there were only two relapses and both of them had Class V nephritis. At four month, the average urine protein creatinine ratio was 0.36 g/gCr, and the average dose of prednisolone was 9.9 mg/day. There were only three episodes of infections which required antibiotics administrations. Conclusions Early sequential combination of mizoribine and tacrolimus seems to be effective and safe for lupus nephritis. Background and aims Interferon (IFN)-as are pivotal in sys-temic lupus erythematosus (SLE), and type III IFNs (IFN-ls) were recently also associated with SLE. We investigated levels of IFN-a and IFN-l1, and related cytokines in SLE patients and controls. Methods We included 261 SLE patients and 261 population controls. All were examined and assessed for current organ manifestations and disease activity/damage using SLAM, SLE-DAI and ACR/SDI scales. Levels of IFN-l1, IFN-a, IL-17A, IL-23 and IP-10 were measured by ELISA. Results IFN-l1 and IFN-a were detected in 29% and 44% of patients respectively, but their levels did not correlate. High

To evaluate the clinical characteristics of Mycobacterium tuberculosis infection in rheumatoid arthritis (RA) patients, we examined the clinical manifestations and radiography/computed tomography (CT) findings in RA patients with tuberculosis (RA+/TB+). A total of 1121 tuberculosis patients were admitted to our hospital from 1995 to 2003, with the RA patients among them comprising 1.8% (20 cases; 9 men and 11 women). This is approximately three times as high as the prevalence of RA in the entire population in Japan. In addition, the RA+/TB+ patients were older and had a longer history of RA than the 140 outpatients in our RA clinic who did not have tuberculosis (RA+/TB-). Half of the RA+/TB+ patients had no symptoms (e.g., cough, sputum, pyrexia), and their tuberculosis was detected accidentally by radiography/CT. The positive rates of the bacilli in the smear and culture of the sputum from the RA+/TB+ patients were lower than those from 143 patients randomly selected from among 1091 tuberculosis patients without any collagen disease including RA (RA-/TB+). The RA+/TB+ patients had a higher incidence of extrapulmonary tuberculosis (30%), including four cases (20%) of miliary tuberculosis, an incidence seven times higher than among the general population of tuberculosis patients. Among 14 cases of pulmonary tuberculosis patients with RA, bilateral lesions and non-cavitary lesions were found in 71.4% and 64.3%, respectively, which tended to be a higher incidence than in the RA-/TB+ patients. The mortality rate and sputum conversion time of the RA+/TB+ patients were no different from those of the RA-/TB+ patients. The prevalence of tuberculosis in RA patients is expected to increase after introduction of anti-cytokine therapy in Japan, and careful observation should be done to avoid this complication in RA patients.

Summary Pathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We, instead, studied the integrity of host's immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host's steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing the guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8 + Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and disease were healed by anti-DOCK8 antibody in the mice including SLE-model (NZBxNZW) F1 mice. Thus, DOCK8 + Tfh cells generated after repeated TCR stimulation by immunogenic form of pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system's self-organized criticality, cause SLE.

To evaluate the clinical characteristics of Mycobacterium tuberculosis infection in rheumatoid arthritis (RA) patients, we examined the clinical manifestations and radiography/computed tomography (CT) findings in RA patients with tuberculosis (RA+/TB+). A total of 1121 tuberculosis patients were admitted to our hospital from 1995 to 2003, with the RA patients among them comprising 1.8% (20 cases; 9 men and 11 women). This is approximately three times as high as the prevalence of RA in the entire population in Japan. In addition, the RA+/TB+ patients were older and had a longer history of RA than the 140 outpatients in our RA clinic who did not have tuberculosis (RA+/TB-). Half of the RA+/TB+ patients had no symptoms (e.g., cough, sputum, pyrexia), and their tuberculosis was detected accidentally by radiography/CT. The positive rates of the bacilli in the smear and culture of the sputum from the RA+/TB+ patients were lower than those from 143 patients randomly selected from among 1091 tuberculosis patients without any collagen disease including RA (RA-/TB+). The RA+/TB+ patients had a higher incidence of extrapulmonary tuberculosis (30%), including four cases (20%) of miliary tuberculosis, an incidence seven times higher than among the general population of tuberculosis patients. Among 14 cases of pulmonary tuberculosis patients with RA, bilateral lesions and non-cavitary lesions were found in 71.4% and 64.3%, respectively, which tended to be a higher incidence than in the RA-/TB+ patients. The mortality rate and sputum conversion time of the RA+/TB+ patients were no different from those of the RA-/TB+ patients. The prevalence of tuberculosis in RA patients is expected to increase after introduction of anti-cytokine therapy in Japan, and careful observation should be done to avoid this complication in RA patients.