Diminished antibody response to SARS-CoV-2 in rheumatoid arthritis compared to metabolic disorders following the primary series of vaccinations and its recovery with a booster: A single-center prospective observational study.

AIM: To compare antibody responses after vaccinations between patients with rheumatoid arthritis (RA) and patients with metabolic disorders (MD). The study places special emphasis on understanding how common diseases affect antibody responses in individuals with RA within real-world settings. METHODS: The participants were 117 patients with RA (66 with RA only and 51 with RA and MD) and 37 patients with MD who received both the primary series of vaccinations and a booster. Antibody titers were compared after the primary series of vaccinations and a booster, and factors influencing the antibody response were assessed. RESULTS: Following the primary series of vaccinations, a significant reduction in antibody titers was observed in patients with longer days between vaccination and antibody measurement, the use of IL-6 inhibitors, selective T cell co-stimulation modulators, and methotrexate. Comorbid MD did not exhibit significant influences on antibody response in RA. Notably, the presence of RA itself was not significant in multivariate linear regression analysis. After the administration of the booster, however, day between vaccination and antibody measurement, the use of IL-6 inhibitor, and methotrexate no longer remained significant. Only the use of selective T cell co-stimulation modulators retained its significance. CONCLUSIONS: MD did not exhibit a significant impact on antibody responses in RA patients. The reduced antibody response following the primary series in RA patients appeared to be attributed more to specific RA medications rather than to the disease itself. Booster vaccines are vital in restoring the antibody response in RA.

Effects of acute simulated microgravity on nocturnal sleep, daytime vigilance, and psychomotor performance: comparison of horizontal and 6 degrees head-down bed rest.

This study examined the effect of acute simulated microgravity on nocturnal sleep, daytime vigilance, and psychomotor performance. Each of 7 volunteers were maintained for 3 days of head-down and horizontal bed rest in a counter-balanced design. Assessment measures were polysomnographic recordings on the first night and performance on psychophysiological tasks on the second day involving subjective and objective vigilance, P300, simple reaction time tasks, and dual performance tasks. No clear difference in sleep structure was observed between the head-down and horizontal conditions, except for a slight decrease in Stage 4 for head-down. Both subjective and objective daytime vigilance, P300, and the simple RT task showed no statistical difference, although tracking performance on the dual task showed deterioration at 10:00 for the head-down condition. These results suggest that nocturnal sleep, daytime vigilance, and psychophysiological functions were not disturbed in head-down sleep conditions, although there was a mild deterioration of higher attentional function in the morning.

Sjögren's syndrome associated with chronic hepatitis C, severe thrombocytopenia, hypertrophic cardiomyopathy, and diabetes mellitus.

A 74-year-old woman with Sjögren's syndrome and chronic hepatitis C (CHC) was admitted to our hospital in October 2003 for treatment of diabetes mellitus. She had the past history of recurrent thrombocytopenia, which was proven to be due to peripheral destruction. Although she had been diagnosed with hypertrophic cardiomyopathy (HCM) for 2 years, she had never felt palpitation. She suddenly died probably of fatal arrhythmia related to HCM during the last hospitalization. Although hepatitis C virus (HCV) infection has been associated with Sjögren's syndrome, thrombocytopenia, HCM, and diabetes mellitus, all these diseases rarely occur in a single patient. It will be necessary to identify similar cases to elucidate the etiopathogenesis of extra-hepatic manifestations of HCV infection.

Effects of FTY720 in MRL-lpr/lpr mice: therapeutic potential in systemic lupus erythematosus.

UNLABELLED: OBJECTIVE To examine the effects of a novel immunosuppressant, FTY720, on hematolymphoid cells and the clinical course of MRL-lpr/lpr (MRL/lpr) mice genetically predisposed to systemic lupus erythematosus (SLE). METHODS: Apoptosis of hematolymphoid cells was determined in vitro by FACScan after staining with propidium iodide or merocyanine 540. From 4 months of age, 15 female MRL/lpr mice received oral administration of 2 mg/kg each of FTY720, methylprednisolone (mPSL), or vehicle, 3 times per week. Therapeutic efficacy was evaluated by levels of anti-dsDNA antibodies in serum and the survival rate. In parallel, T cell proliferation and secretion of interleukin 2 (IL-2) induced by anti-CD3, phenotypes of the spleen, lymph node and bone marrow cells, as well as immunohistochemistry of the kidney, were examined in vitro. RESULTS: FTY720 at 2 microM induced apoptosis in more than 70% of double negative (CD4-/CD8-) T cells from the spleen of MRL/lpr mice in vitro. Oral FTY720 was tolerated well with no apparent side effects. FTY720 treated and control mice gained weight at an identical pace through to 9 months of age. FTY720 significantly suppressed the production of anti-dsDNA antibodies (FTY720 vs control: 1739 +/- 898 U/ml vs 410 +/- 356 U/ml at 8 months of age; p < 0.05) and reduced the deposition of IgG in glomeruli compared to control animals. At 9 months of age, the survival rate in the FTY720 treated mice was 86.9% compared to 33.0% in controls (p < 0.01). FTY720 decreased the number of double negative T cells from the spleen and lymph nodes in vivo, and increased T cell proliferation and IL-2 secretion induced by anti-CD3 stimulation in vitro. CONCLUSION: FTY720 suppressed the development of autoimmunity and prolonged the lifespan of female MRL/lpr mice. Suppression of autoimmunity, at least in part, may have resulted from an apoptogenic potential of FTY720. Hence, it could be useful for primary or adjunctive therapy of human SLE.