Volume 213, Issue 2, August 2023

Fewer peripheral tolerogenic DCs in patients with food allergy. The abundance of tolerogenic DCs is associated with epithelial cell-derived galectin-9. Peripheral type 1 regulatory T cells are associated with serum galectin-9 and the frequency of tolerogenic DCs.

Memory B cells are essential for our immunological memory and respond rapidly to reinfection. CD27 is a widely used cell surface marker for human memory B cells and is gradually upregulated during the germinal centre reaction. Here, an overview of recent data on human CD27+ memory B cells is presented with emphasis on function and immunoglobulin sequencing.

During an infection, plasmablasts circulating in blood represent ongoing formation of antibody-producing cells from activated B cells. Here we study the early plasmablasts in previously naïve COVID-19 patients arriving at hospital. We find extensive cross-reactivity to circulating and non-circulating beta-coronaviruses, that IgA1 responses dominate, and that the cells express markers suggesting mucosal homing.

The main findings in the present study are (i) a reduced frequency and (ii) altered phenotype of CD24hiCD27+ putative Breg cells in patients with GPA/PR3-ANCA+ vasculitis compared with HC, and (iii) that induced Breg cells during remission could regulate T-cell proliferation and production of certain cytokines but failed to regulate IFN-? and TNF production. In line with the latter observation, IFN-?, and its induced chemokine CXCL10, were elevated in the circulation.

NETs can act on different cells to release large amounts of cytokines and activate the inflammasome, which can subsequently aggravate the inflammatory response. Based on the idea that NETs may be proinflammatory DAMPs of IIMs, we describe the role of NETs, DAMPs, and their interaction in the pathogenesis of IIMs and discuss the possible targeted treatment strategies in IIMs.

Cell-free DNA (cfDNA) from patients with rheumatoid arthritis (RA) activates NF-κB via the toll-like receptor 9 (TLR-9) signalling pathway in vitro. Tocilizumab, but not tumour necrosis factor inhibitors, decreases cfDNA levels in RA patients and RA-associated fibroblast-like synoviocytes. Tocilizumab degrades cfDNA at clinically relevant concentrations, suggesting tocilizumab likely controls inflammation in RA by suppressing TLR-9-dependent NF-κB signalling.

Complement was involved in the anti-tumor effect of hyperthermia in vitro. Hyperthermia markedly increased the expression of heat shock protein 5 (HSPA5) and decreased the expression of CD55 which regulated the activation of complement C3 and complement cascade. Activation of HSPA5/NFκB (P65) signaling pathway resulted in a decrease in CD55 expression.

We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred.

We find raised levels of anti-DSG2 autoantibodies in sera from individuals following severe COVID-19. Staining of post-mortem cardiac tissue from individuals that died from COVID-19 with an anti-DSG2 antibody revealed disruption of the intercalated disc between cardiomyocytes that was consistent with separation of the DSG2 protein homodimer. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection.

Transplant-associated thrombotic microangiopathy (TA-TMA) complicates up to 30% of allogeneic stem cell transplants and is a significant cause of mortality. Positive feedback loops among complement, pro-inflammatory, pro-apoptotic, and coagulation cascades are involved in the endotheliopathy underlying this condition, with MASP2 and the lectin pathway a major component. Utilizing RNAseq and ex vivoand in vitromodels with patient plasmas, we identified a plausible mechanism by which the MASP2 inhibitor narsoplimab could protect against endothelial cell injury in TA-TMA, as illustrated in this figure.