S100a9 Protects Male Lupus-Prone NZBWF1 Mice From Disease Development

Systemic lupus erythematosus (SLE) is an autoimmune disorder disproportionally affecting women. A similar sex difference exists in the murine New Zealand Black/White hybrid model (NZBWF1) of SLE with all females, but only 30-40% of males, developing disease within the first year of life. Myeloid-derived suppressor cells (MDSCs) are prominent in NZBWF1 males and while depletion of these cells in males, but not females, promotes disease development, the mechanism of suppression remains unknown. S100a9, expressed by neutrophils and MDSCs, has previously been shown to exert immunosuppressive functions in cancer and inflammation. Here we investigated if S100a9 exerts immunosuppressive functions in NZBWF1 male and female mice. S100a9+/+, S100a9+/- and S100a9-/- NZBWF1 mice were followed for disease development for up to 8 months of age. Serum autoantibody levels, splenomegaly, lymphocyte activation, glomerulonephritis and proteinuria were measured longitudinally or at the time of harvest. In accordance with an immunosuppressive function of MDSCs in male mice, S100a9-deficient male NZBWF1 mice developed accelerated autoimmunity as indicated by increased numbers of differentiated effector B and T cells, elevated serum autoantibody levels, increased immune-complex deposition and renal inflammation, and accelerated development of proteinuria. In contrast, female mice showed either no response to S100a9-deficiency or even a slight reduction in disease symptoms. Furthermore, male, but not female, S100a9-/- NZBWF1 mice displayed an elevated type I interferon-induced gene signature, suggesting that S100a9 may dampen a pathogenic type I interferon signal in male mice. Taken together, S100a9 exerts an immunosuppressive function in male NZBWF1 mice effectively moderating lupus-like disease development via inhibition of type I interferon production, lymphocyte activation, autoantibody production and the development of renal disease.

Elevation of autoantibodies to cerebral proteins in hepatic encephalopathy: Another pathogenic factor?

Background: The pathophysiology of hepatic encephalopathy is incompletely understood. It remains illusive how the contributing factors of neuronal ammonia accumulation, cell swelling and inflammation interact. Objective: Correlation of neuronal autoantibody levels to the degree of hepatic encephalopathy as first indication of immune mediated pathogenesis. Methods: We investigated serum autoantibody levels of representative brain proteins in patients with hepatic encephalopathy as well as in an experimental rat model with cirrhosis and hepatic encephalopathy after carbon tetrachloride exposure. They were examined in relation to presence of hepatic encephalopathy and the degree of neurological impaiment evaluated by quantitative scores. Results: In hepatic encephalopathy an increase of all of the examined antibodies was observed in serum. The grade of antibody elevation correlated to the degree of encephalopathy registered by quantitative evaluation of brain dysfunction. Conclusion: The degree of hepatic encephalopathy parallels neuronal autoantibody elevation. In case a causal relationship could finally be established, it adds to the understanding of hepatic encephalopathy and may open a new perspective for treatment of this handicaping condition by immunosuppressive strategies.

Immunoserologic Detection and Diagnostic Relevance of Cross-Reactive Autoantibodies in Coronavirus Disease 2019 Patients

Background During the coronavirus disease 2019 (COVID-19) pandemic, we detected a new immunofluorescence (IF) pattern in serum autoantibody (autoAb) screening of laboratory-confirmed COVID-19 patients. Methods The IF pattern was composed of liver and gastric mucosa staining on rat kidney/liver/stomach sections. Results We describe 12 patients positive for the cross-reactive antibody, compared with a negative group of 43 hospitalized COVID-19 patients, finding association with either neurologic or thrombotic complications. In sequential pre- and post-COVID-19 serum samples, we confirmed autoAb seroconversion. Conclusions Our data indicate that autoAb screening in COVID-19 patients may be easily performed by IF and alert for autoreactive-mediated complications such as thrombotic or neurologic events.

The Effects of Alternate-Day Corticosteroids in Autoimmune Disease Patients

Introduction. Several studiesdemonstrated that the use of alternate-day corticosteroid therapy maintains control of autoimmune diseases due to the prolongation of their therapeutic effect beyond their metabolic effect, with a significant decrease in side effects in patients. For this reason, the current recommendation for the use of these medications is in a short cycle to avoid adverse effects when used frequently and for prolonged periods of time. Objectives. To learn variations in serum levels of autoantibodies in autoimmune diseases treated with steroids on alternate days, as well as whether there are differences in the response to them depending on the type of disease. Study Design. A descriptive, retrospective, and cross-sectional study was conducted in which serum autoantibody levels were compared at the time of diagnosis and three months after alternate-day corticosteroid therapy. Results. We included 106 patients from three autoimmune connective tissue diseases (systemic lupus erythematosus, Sjögren syndrome, and Hashimoto’s thyroiditis) and observed a statistically significant decrease in serum autoantibody levels both in patients with lupus and those with Hashimoto’s thyroiditis, regardless of the sex of the patients, as well as the type of steroids used. Conclusions. Treatment with alternate-day corticosteroids achieved a statistically significant decrease in serum autoantibody levels in patients with systemic lupus erythematosus and Hashimoto’s thyroiditis.

Spinal Surgery- Use of Dexmedetomidine for Myasthenia Grvis - A Case Report

Myasthenia gravis (MG) is a chronic autoimmune disease in which autoantibodies destroy acetylcholine receptors at motor end plat of neuromuscular junction which prevent skeletal muscle depolarization and contraction, causes muscle weakness and tiredness upon exertion with a tendency to be subsided after taking some rest or after taking anticholinesterase medication. Symptoms of progression of MG include the involvement of upper and lower extremities and muscle weakness that leads to inability in doing basic motor functions. The diagnosis of myasthenia gravis includes sign and symptoms, clinical examination and laboratory investigation of serum autoantibody (AChR autoantibodies) implicated in the disease pathology. Surgical procedures under general anesthesia in a patient with MG could be very challenging for an anesthetist because of pathophysiological manifestations of the disease. We report a case of a patient undergoing 4 level spinal fixation with coexistent myasthenia gravis (according to Osserman II B), requiring general anesthesia for spinal surgery in prone position. Myasthenia gravis affects the neuromuscular junction that is why it has a great significance of interest for the anesthetist.