IgG immune complexes are of central importance in the humoral immune system and strongly implicated in the pathogenesis of hematologic and rheumatic autoimmune disorders. Cross-linking of receptors for the Fc domain of IgG antibodies (FcgammaRs) triggers a wide variety of effector functions including phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators, as well as immune complex clearance and regulation of antibody production. In this way, FcgammaR provide an essential feedback between the humoral and cellular immune response. In the past, significant advances have been made in the molecular dissection of FcgammaR function using cellular transfection systems. Current approaches designed to target and change individual FcgammaR genes in mice have given further insight into their specific contributions to systemic processes, also indicating them to be important immunoregulatory receptors involved in various disease states of allergy, autoimmunity, and inflammation. Future work on targeting FcgammaR binding sites in combination with humanized FcgammaR mouse models will lead to novel therapeutic strategies in the treatment of IgG-mediated human disease in which FcgammaR activation plays an integral part.

The YadA surface protein of enteropathogenic Yersinia species contains two highly hydrophobic regions: one close to the amino terminal, and the other at the carboxy-terminal end of the YadA polypeptide. To study the role of these hydrophobic regions, we constructed 66 bp deletion mutants of the yadA genes of Yersinia enterocolitica serotype O:3 strain 6471/76 (YeO3) and of O:8 strain 8081 (YeO8). The mutant proteins, YadAYeO3-delta 83-104 and YadAYeO8-delta 8O-101, lacked 22 amino acids from the amino-terminal hydrophobic region, formed fibrillae and were expressed on the cell surface. Bacteria expressing the mutated protein lost their auto-agglutination potential as well as their collagen-binding property. Binding to fibronectin and laminin was affected differently in the YeO3 and the YeO8 constructs. The deletion did not influence YadA-mediated complement inhibition. Loss of the collagen-binding property was associated with loss of virulence in mice. We also constructed a number of YadAYeO3 deletion mutants lacking the hydrophobic carboxy-terminal end of the protein. Deletions ranging from 19 to 79 amino acids from the carboxy terminus affected polymerization of the YadA subunits, and also resulted in the loss of the YadA expression on the cell surface. This suggests that the carboxy terminus of YadA is involved in transport of the protein to the bacterial outer surface.

Background: Vitamin D has a wide variety of physiological functions in the human body. There is increasing evidence that low serum levels of this vitamin have an important role in the pathogenesis of different skeletal and extra-skeletal diseases. Vitamin D deficiency and insufficiency is common at northern latitudes. There are few population-based studies in the northern European region looking at the issue in a wider age group. We aimed to measure Vitamin D level in the general population of Estonia (latitude 59°N), a North-European country where dairy products are not fortified with vitamin D.

SARS-CoV-2 infection has a risk to develop into life-threatening COVID-19 disease. Whereas age, hypertension, and chronic inflammatory conditions are risk factors, underlying host factors and markers for disease severity, e.g. requiring intensive care unit (ICU) treatment, remain poorly defined. To this end, we longitudinally profiled blood inflammation markers, antibodies, and 101 plasma proteins of hospitalized COVID-19 patients who did or did not require ICU admission. While essentially all patients displayed SARS-CoV-2-specific antibodies and virus-neutralization capacity within 12–15 days, a rapid, mostly transient upregulation of selective inflammatory markers including IL-6, CXCL10, CXCL11, IFNγ, IL-10, and monocyte-attracting CCL2, CCL7 and CCL8, was particularly evident in ICU patients. In addition, there was consistent and sustained upregulation of apoptosis-associated proteins CASP8, TNFSF14, HGF, and TGFB1, with HGF discriminating between ICU and non-ICU cohorts. Thus, COVID-19 is associated with a selective inflammatory milieu within which the apoptotic pathway is a cardinal feature with potential to aid risk-based patient stratification.

Data availabilitySummary statistics generated by COVID-19 Host Genetics Initiative are available online (https://www.covid19hg.org/results/r6/). The analyses described here use the freeze 6 data. The COVID-19 Host Genetics Initiative continues to regularly release new data freezes. Summary statistics for samples from individuals of non-European ancestry are not currently available owing to the small individual sample sizes of these groups, but the results for 23 loci lead variants are reported in Supplementary Table 3. Individual-level data can be requested directly from the authors of the contributing studies, listed in Supplementary Table 1.

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The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three‐dimensional structured illumination microscopy (3D‐SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D‐SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA‐free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM. J. Cell. Biochem. 116: 704–710, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.

Profiling antibodies to SARS‐CoV‐2 can help to assess potential immune response after COVID‐19 disease. Luciferase IP system (LIPS) assay is a sensitive method for quantitative detection of antibodies to antigens in their native conformation. We here describe LIPS to detect antibody responses to SARS‐CoV‐2 spike (S) and nucleocapsid (N) proteins in COVID‐19 patients. The antibodies targeted both S and N fragments and gave a high assay sensitivity by identifying 26 out of 26 COVID‐19 patients with N antigen or with three protein fragments when combined into a single reaction. The assay correlated well with ELISA method and was specific to COVID‐19 as we saw no reactivity among uninfected healthy controls. Our results show that LIPS is a rapid and measurable method to screen antibody responses against SARS‐CoV‐2 antigens.