The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM+ and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM+, switched (IgA+/IgG+), IgM+ only, IgD+ only, and CD27- (IgA+/IgG+/IgM+)] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.
Rotavirus is the most important worldwide cause of severe gastroenteritis in infants and young children. Intestinal epithelial cells are the principal targets of rotavirus infection, but the response of enterocytes to rotavirus infection is largely unknown. We determined that rotavirus infection of HT-29 intestinal epithelial cells results in prompt activation of NF-κB (<2 h), STAT1, and ISG F3 (3 h). Genetically inactivated rotavirus and virus-like particles assembled from baculovirus-expressed viral proteins also activated NF-κB. Rotavirus infection of HT-29 cells induced mRNA for several C-C and C-X-C chemokines as well as IFNs and GM-CSF. Mice infected with simian rotavirus or murine rotavirus responded similarly with the enhanced expression of a profile of C-C and C-X-C chemokines. The rotavirus-stimulated increase in chemokine mRNA was undiminished in mice lacking mast cells or lymphocytes. Rotavirus induced chemokines only in mice <15 days of age despite documented infection in older mice. Macrophage inflammatory protein-1β and IFN-stimulated protein 10 mRNA responses occurred, but were reduced in p50−/− mice. Macrophage inflammatory protein-1β expression during rotavirus infection localized to the intestinal epithelial cell in murine intestine. These results show that the intestinal epithelial cell is an active component of the host response to rotavirus infection.
Objectives To determine the prevalence of antibodies to SARS-CoV-2 and the incidence of seroconversion in the first month of follow-up among interns, residents, and medical doctors attending patients at a University Hospital, to explore for associations of seroprevalence and seroconversion with risk factors and symptoms compatible with COVID-19, and to explore the concordance of CLA, LFA, and ELFA. Design or methods We conducted a cross-sectional and a prospective study among medical doctors and medical trainees at Hospital Universitario San Ignacio in Bogota (Colombia) during June, July, and August to assess seroprevalence and seroconversion rates in this population was performed using CLA IgG for SARS-CoV-2. LFA IgG and IgM and ELFA IgM were also determined to explore concordance with CLA IgG. Results At baseline, 8 (2.28% 95%CI 1.16-4.43%) individuals were IgG positive for SARS-CoV-2 by CLA. At the end of the study, 21 (5.98% 95%CI 3.94-8.97%) individuals seroconverted by CLA IgG. In all, 29 individuals had IgG by CLA and of these 11 (3.13% 95%CI 1.76-5.52%) were asymptomatic. No associations with risk factors for infection were identified. CLA had moderate concordance with LFA IgG and ELFA, but minimal with LFA IgM. Conclusions Our report is one of the first in Latina America on seroprevalence and seroconversion rates in medical healthcare workers. It emphasizes the importance of avoiding focusing only on symptomatic individuals to screen this population for SARS-CoV-2 infection, since of all individuals that have evidence of previous infection many (37.93%) may be pre-symptomatic or asymptomatic and may contribute to infection/disease spread.
Treatment of human synovial cells with interleukin‐1 (IL‐1) results in a large increase in the production of prostaglandin E, (PGE2), a function in which the activation of phospholipase A2 (PLA2) is a key step. In order to identify the enzymes that are linked to IL‐1‐mediated arachidonate availability and subsequent PGE2 production, we have investigated the changes in gene expression of the 85‐kDa cytosolic PLA2 (cPLA2), the 14‐kDa secretory PLA2 (sPLA2) and the two forms of cyclooxygenase in human synoviocytes after stimulation with recombinant IL‐1β. Northern‐blot analysis revealed that both cPLA2 and cyclooxygenase‐2 mRNA were progressively upregulated upon exposure to IL‐1 for 5 hours and the glucocorticoid, dexamethasone, blocked the increased expression of these two genes. In contrast, IL‐1‐induced sPLA2 gene expression determined in the same cell samples was weak and most often rapid, and dexamethasone further stimulated it. In addition, IL‐1 did not modify the levels of the constitutive cyclooxygenase‐1. The cPLA2 and cyclooxygenase‐2 enzymic activities are dependent upon de novo synthesis of mRNA and protein, since they were inhibited by actinomycin D and cycloheximide. Our data suggest that the IL‐1‐induced production of PGE2 in human synoviocytes can be attributed to the stimulation of both cPLA2 and cyclooxygenase‐2. These enzymes may represent appropriate targets for selective blockade of prostanoid production in the inflammed joints.
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