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Background A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c+ B-cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c+ B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with high autoantibody production. The purpose of this study was to explore the role of CD11c+ B cells in the pathogenesis of lupus in cGVHD mice. Methods cGVHD was induced by an intraperitoneal injection of 5 × 107 Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants. Results The percentage and absolute number of CD11c+ B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c+ plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c+ B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c+ B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet+CD11c+ B cells increased in lupus patients and positively correlated with serum antichromatin levels. Conclusion T-bet+CD11c+ B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet+CD11c+ B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment.

Intellectual property in India is a subordinate office of the Govt of India & administers the Indian law for Patents, Designs, Trade Marks & Geographical Indica

Background A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c+ B-cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c+ B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with high autoantibody production. The purpose of this study was to explore the role of CD11c+ B cells in the pathogenesis of lupus in cGVHD mice. Methods cGVHD was induced by an intraperitoneal injection of 5 × 107 Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants. Results The percentage and absolute number of CD11c+ B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c+ plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c+ B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c+ B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet+CD11c+ B cells increased in lupus patients and positively correlated with serum antichromatin levels. Conclusion T-bet+CD11c+ B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet+CD11c+ B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment.

Objective. Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) are clinically quiescent despite serologic activity. Since studies suggest that antichromatin antibodies are more sensitive than anti-dsDNA antibodies in detecting active SLE, and that immunoglobulin (Ig) G, in particular complement-fixing subclasses, may be more pathogenic than IgM, we investigated the levels of anti-dsDNA and antichromatin isotypes in SACQ patients as compared to non-SACQ patients with SLE. Methods. Levels of IgM, IgA, IgG, and IgG1–4 antichromatin and anti-dsDNA were measured by ELISA. SACQ was defined as ≥ 2 years with the SLE Disease Activity Index 2000 (SLEDAI-2K) at 2 or 4 from serologic activity, during which patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Unselected non-SACQ patients with SLE were used as comparators. SACQ patient serum samples were further stratified based on subsequent development of flare, defined as clinical SLEDAI-2K ≥ 1 and/or treatment initiation. Nonparametric statistics were used, and generalized estimating equations were applied to account for multiple samples in the same patient. Results. SACQ patients’ complement-fixing antichromatin and anti–dsDNA IgG subclasses were significantly higher than those of non-SACQ patients. When the sample drawn latest in a SACQ period was analyzed, there was no difference between antichromatin or anti-dsDNA isotype or IgG subclass levels between patients who flared and those who remained SACQ, nor were consistent trends seen when samples were examined during SACQ and flare in the same patient. Conclusion. The SACQ phenotype does not arise from a lack of pathogenic anti-dsDNA and/or antichromatin autoantibodies. Neither increases in antichromatin nor anti-dsDNA isotype or IgG subclass levels were predictive of or coincident with flare in SACQ patients.

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Objective. Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) are clinically quiescent despite serologic activity. Since studies suggest that antichromatin antibodies are more sensitive than anti-dsDNA antibodies in detecting active SLE, and that immunoglobulin (Ig) G, in particular complement-fixing subclasses, may be more pathogenic than IgM, we investigated the levels of anti-dsDNA and antichromatin isotypes in SACQ patients as compared to non-SACQ patients with SLE. Methods. Levels of IgM, IgA, IgG, and IgG1–4 antichromatin and anti-dsDNA were measured by ELISA. SACQ was defined as ≥ 2 years with the SLE Disease Activity Index 2000 (SLEDAI-2K) at 2 or 4 from serologic activity, during which patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Unselected non-SACQ patients with SLE were used as comparators. SACQ patient serum samples were further stratified based on subsequent development of flare, defined as clinical SLEDAI-2K ≥ 1 and/or treatment initiation. Nonparametric statistics were used, and generalized estimating equations were applied to account for multiple samples in the same patient. Results. SACQ patients’ complement-fixing antichromatin and anti–dsDNA IgG subclasses were significantly higher than those of non-SACQ patients. When the sample drawn latest in a SACQ period was analyzed, there was no difference between antichromatin or anti-dsDNA isotype or IgG subclass levels between patients who flared and those who remained SACQ, nor were consistent trends seen when samples were examined during SACQ and flare in the same patient. Conclusion. The SACQ phenotype does not arise from a lack of pathogenic anti-dsDNA and/or antichromatin autoantibodies. Neither increases in antichromatin nor anti-dsDNA isotype or IgG subclass levels were predictive of or coincident with flare in SACQ patients.

As the potential for and scope of some types of disasters increases, so too does the need to build greater disaster resilience across the globe. Communities ideally begin building resilience prior to experiencing a disaster in order to reduce negative impacts and ease recovery processes; however, nu …

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