Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

Idiopathic inflammatory myopathies (IIMs) are a group of rare, acquired autoimmune diseases characterized by profound muscle weakness and immune cell invasion into non-necrotic muscle. They are related to the presence of antibodies known as myositis-specific antibodies and myositis-associated antibodies, which are associated with various IIM phenotypes and the clinical prognosis. The possibility of the participation of other pathological mechanisms involved in the inflammatory response in IIM has been proposed. Such mechanisms include the overexpression of major histocompatibility complex class I in myofibers, which correlates with the activation of stress responses of the endoplasmic reticulum (ER). Taking into account the importance of the ER for the maintenance of homeostasis of the musculoskeletal system in the regulation of proteins, there is probably a relationship between immunological and non-immunological processes and autoimmunity, and an example of this might be IIM. We propose that ER stress and its relief mechanisms could be related to inflammatory mechanisms triggering a humoral response in IIM, suggesting that ER stress might be related to the triggering of IIMs and their auto-antibodies' production.

Impaired muscle strength is associated with ultrastructure damage in myositis.

The muscle fiber ultrastructure in Idiopathic Inflammatory Myopathies (IIM) has been scarcely explored, especially in Inclusion Body Myositis. The aim of this study was to implement the Scanning Electron Microscopy (SEM) in a small cohort of IIM patients, together with the characterization of immunological profile for a better understanding of the pathophysiology. For immunological profile characterization, we identified the presence of autoantibodies (Ro-52, OJ, EJ, PL7, PL12, SRP, Jo-1, PMScl75, PMScl100, Ku, SAE1, NXP2, MDA5, TIF1γ, Mi-2α, Mi-2ß) and quantified cytokines (IL-1ß, IFN-α2, IFN-γ, TNF-α, IL-6, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33) and chemokines (CCL2, CXCL8). The histological analysis was made by hematoxylin-eosin staining while the muscle fiber ultrastructure was characterized by SEM. We observed changes in the morphology and structure of the muscle fiber according to muscle strength and muscle enzymes. We were able to find and describe muscle fiber ultrastructure with marked irregularities, porosities, disruption in the linearity and integrity of the fascicle, more evident in patients with increased serum levels of muscle enzymes and diminished muscle strength. Despite the scarce reports about the use of SEM as a tool in all clinical phenotypes of IIM, our work provides an excellent opportunity to discuss and reframe the clinical usefulness of SEM in the diagnostic approach of IIM.

Suicide Risk in Rheumatoid Arthritis Patients is Associated With Suboptimal Vitamin D Levels.

BACKGROUND/OBJECTIVE: Rheumatoid arthritis (RA) patients might experience anxiety and depressive symptoms. Deficient vitamin D levels may be a trigger for these conditions. The aim of this study was to determine the frequency of depression, anxiety symptoms, and suicidal risk or ideation in patients with RA associated with vitamin D serum levels. METHODS: In this cross-sectional study, we recruited RA patients older than 18 years, classified into 3 groups according to serum vitamin D levels: sufficient, ≥30 ng/mL; insufficient, 20-29 ng/mL; and deficient, <20 ng/mL. Based on the self-reported Plutchik and the Hospital Anxiety and Depression Scale, we evaluated the association of suicidal risk, depression, and anxiety with the vitamin D levels in RA and the Rheumatoid Arthritis Quality-of-Life Questionnaire. RESULTS: We studied 72 patients with RA between January and October 2019. We found an inverse correlation between Plutchik score and suicidal risk with inadequate vitamin D levels, but not with the Hospital Anxiety and Depression Scale. Suicidal ideation was associated with a higher score on the Rheumatoid Arthritis Quality-of-Life Questionnaire. CONCLUSIONS: Despite the high prevalence of depressive and anxiety symptoms in RA patients, a Plutchik low correlation coefficient with inadequate serum levels of vitamin D was found. However, in the analysis of covariance, we were able to find that vitamin D levels remain associated with a reduction of suicide ideation. Further studies are needed to identify a risk profile for early psychological interventions to improve the quality of life in RA patients.

Gene expression profile involved in signaling and apoptosis of osteoblasts in contact with cellulose/MWCNTs scaffolds.

The aim of this work was to evaluate the expression profile of genes involved in signaling, intracellular and extracellular Ca+2 concentration and apoptosis pathways of osteoblasts in contact with a scaffold made of a composite of BCN/MWCNTs. Osteoblasts were cultivated on BCN, MWCNTs and their mixtures. Osteoblast RNA was extracted for sintering cDNA to amplify genes of interest by PCR; intra- and extracellular calcium (Ca2+) was also quantified. Regarding the genes that participate in the regulation paths (MAPK and NF-KB), it was found that only the expression of NF-KB was affected in all treatments. The expression of VEGFA increased, except in the treatment of high concentration of MWCNTs, where remained unchanged. The expression of genes Apaf-1 and Bcl-2/Bax and TP53 increased as compared to the control (except for TP53 in BC and C1/MWCNTs) indicating that cells are responding to the presence of BCN-MWCNTs composites scaffolds. The results suggest that osteoblast developed a modification in the expression profile of genes that actively participate in cellular processes such as proliferation, vasculogenesis and apoptosis, which may be modulated by the increase of intra- and extracellular Ca2+ concentration.

Succinic acid production with Actinobacillus succinogenes ZT-130 in the presence of succinic acid.

Glucose fermentation with Actinobacillus succinogenes was carried out at different initial concentrations of succinic acid (SA(0)) to determine its effect on growth and on the production of succinic acid itself. The specific rates of biomass production, succinic, formic and acetic acids decreased with SA(0) (0-40 g/l). The partially dissociated form of succinic acid had a higher effect on cell growth and production of succinic acid as compared to the non-dissociated forms of the acids, a fact that has not been reported until now. Cell growth fitted the Jerusalimski model, and the Aiba-Shoda model was suitable for quantification of the inhibition for the production of succinic acid. The growth inhibition constants K(is) and K(ip) and their summatory were consistent with the experimental values obtained, i.e., 22 g/l for the produced acids and 38 g/l for total acids that were the limits at which the biomass formation ceased.