Much progress has been made in recent years on the diagnostic value, Ag specificity, and pathogenic roles of autoantibodies correlated to the development of rheumatoid arthritis (RA) in humans. However, carbohydrate Ag-specific autoantibodies that may also play important roles in RA have largely been ignored. In this article, we report that serum levels of Abs capable of recognizing α1,4-polygalacturonic acid [(PGA); major structural component of pectin] strongly correlate with RA in humans. The measurements of PGA-specific Abs (PGA-Abs) in sera are comparable to rheumatoid factors and anti-cyclic citrullinated peptide Abs as serological diagnostic markers for RA in terms of sensitivity and specificity. Immunohistochemical staining results indicate that the PGA-Abs selectively bound synovial membrane cells and chondrocytes in the joints of both humans and rabbits (but not rodents). Induction of PGA-Abs by s.c. immunization of rabbits with carrier protein-conjugated synthetic PGA led to severe inflammatory reactions (synovial hyperplasia, small vessel proliferation, and inflammatory cell infiltration) in the joints. Injection of affinity purified anti-PGA IgG into the synovial cavity of rabbits resulted in accumulation of proinflammatory cytokines such as TNF-α, IL-8, and IL-1β in synovial fluid, as well as local pathological damage. We conclude that the PGA-cross-reactive moiety represents a major autoantigen in the joints and can be targeted by autoantibodies capable of triggering arthritogenic responses in vivo.
The purpose of this study was to examine the hepatic bacterial composition and metabolome characteristics of patients with NAFLD using 16S rDNA sequencing and metabolomics. The results of the study revealed substantial differences in hepatic bacterial composition and metabolites between the NAFLD group and the control group. These differences were used to identify potential biomarkers that could be employed to diagnose NAFLD. Liver tissues from 13 patients in the NAFLD group and 12 patients in the control group were collected for microbiota examination. The bacterial DNA profiles of the liver were significantly different between NAFLD patients and controls. NAFLD patients exhibited an enrichment of Enterobacterales, Mycobacteriales, Pseudomonadales, Flavobacteriales and Xanthomonadales, Sphingomonadales, Lysobact, which was characterised by a lack of erales. At the genus level, the abundance values of Escherichia-Shigella, Rhodococcus, and Chryseobacterium in the NAFLD group were significantly elevated, while the abundance values of Stenotrophomonas, Lawsonella and Sphingobium were significantly reduced. A total of 402 distinct metabolites were identified between the two groups, with 78 metabolites that were up-regulated and 14 metabolites that were down-regulated. The enrichment of metabolic pathways indicated that linoleic acid metabolism was the most significant contributor to the metabolic differences, and lipid metabolism was substantially differentiated. The hepatic metabolite levels were substantially correlated with the changes in hepatic microflora, as demonstrated by the correlation analysis. Differences in pathogenesis and host physiological function of NAFLD may be attributed to the hepatic flora and metabolomic characteristics. In the future, this presents new opportunities for the investigation of prospective diagnostic and therapeutic targets for NAFLD.
The M1 and M2 states of macrophage are the two extremes of a physiologic/phenotypic continuum that is dynamically influenced by environmental signals. Molecular mechanism analysis indicated that they gain M1 and M2-related functions after encountering specific ligands in the tissue environment. Here, we first characterized the previously unknown immunobiological functions of mouse Tmem106a. This protein is abundantly expressed on the surface of mouse macrophages. Activation of Tmem106a by stimulation with anti-Tmem106a upregulated the expression of CD80, CD86, CD69 and MHC II on macrophage, and induced the release of TNF-α, IL-1β, IL-6, CCL2 and NO, but not IL-10. These effects were largely abrogated by pretreatment with siRNA against Tmem106a. Notably, anti-Tmem106a significantly increased iNOS production and phosphorylation of STAT1, and had no effect on the ARGINASE-1 or p-STAT6 level, indicating that anti-Tmem106a activated macrophages and polarized them into M1-like macrophages. Further analysis found that anti-Tmem106a stimulation increased phosphorylation of ERK-1/2, JNK, p38 MAPK, NF-κB p65 and IKKα/β, and promoted nuclear translocation of the cytosolic NF-κB p65 subunit. Collectively, these data suggest that mouse Tmem106a might be a new trigger of macrophage activation and have some influence toward the M1 state through the activation of the MAPKs and NF-κB pathway.
Abstract Introduction Immune cells and molecules are considered as clinical biomarkers and potential targets for immunotherapy. Analyses of the composition of peripheral blood cells hold promise for providing a basis for diagnosing and prognosis lung cancer. In this study, we assessed correlations between immune cell subset profiles in peripheral blood and disease prognosis in patients with lung cancer. Methods One hundred and thirteen patients with lung cancer and 99 age‐matched healthy people were enrolled in this study. The percentage and cell count of monocytes, neutrophils, T cells, B cells, natural killer (NK), and NKT cells in peripheral blood were analyzed by flow cytometry or peripheral blood analyzer. Serum cytokines and colony‐stimulating factors were detected by enzyme‐linked immunosorbent assay (ELISA). Results A reduction in antitumor NK cells ( p < 0.0001) and an increase in the protumor MDSCs ( p < 0.0001) were observed in the lung cancer patients compared with the controls. Monocyte counts were significantly higher in lung cancer patients with histories of smoking ( p < 0.05) or drinking ( p < 0.01) than in patients with no relevant history or healthy controls. The number of neutrophils and the neutrophil‐to‐lymphocyte ratio (NLR) were particularly higher in patients with liver metastasis ( p < 0.01) compared with no metastasis patients or healthy controls. Levels of the monocyte‐derived cytokine interleukin‐6 ( p < 0.05), granulocyte colony‐stimulating factor (G‐CSF) ( p < 0.0001), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) ( p < 0.0001) were higher in patients than in controls. G‐CSF levels decreased during the remission phase ( p < 0.05), and positively correlated with carbohydrate antigen 19–9 ( p < 0.05) and gene mutation ( p < 0.05). Conclusion Monocyte and neutrophil counts were higher in peripheral blood in lung cancer patients than in controls, especially when patients had histories of smoking, drinking, and liver metastasis. Serum levels of G‐CSF and GM‐CSF were higher in lung cancer patients, and G‐CSF levels positively correlated with disease severity.
Abstract Antibodies have a common structure consisting of two identical heavy (H) and two identical light (L) chains. It is widely accepted that a single mature B cell produces a single antibody through restricted synthesis of only one V H DJ H (encoding the H-chain variable region) and one V L J L (encoding the L-chain variable region) via recombination. Naive B cells undergo class-switch recombination (CSR) from initially producing membrane-bound IgM and IgD to expressing more effective membrane-bound IgG, IgA, or IgE when encountering antigens. To ensure the “one cell — one antibody” paradigm, only the constant region of the H chain is replaced during CSR, while the rearranged V H DJ H pattern and the L chain are kept unchanged. To define those long-standing classical concepts at the single-cell transcriptome level, we applied the Chromium Single-Cell Immune Profiling Solution and Sanger sequencing to evaluate the Ig transcriptome repertoires of single B cells. Consistent with the “one cell — one antibody” rule, most of the B cells showed one V(D)J recombination pattern. Intriguingly, however, two or more V H DJ H or V L J L recombination patterns of IgH chain or IgL chain were also observed in hundreds to thousands of single B cells. Moreover, each Ig class showed unique V H DJ H recombination pattern in a single B-cell expressing multiple Ig classes. Together, our findings reveal an unprecedented presence of multi-Ig specificity in some single B cells, implying regulation of Ig gene rearrangement and class switching that differs from the classical mechanisms of both the “one cell — one antibody” rule and CSR.
Psoriasis is a chronic inflammatory skin disease with etiologies related to genetics, immunity, and the environment. It is characterized by excessive proliferation of keratinocytes and infiltration of inflammatory immune cells. Glycosylation is a post-translational modification of proteins that plays important roles in cell adhesion, signal transduction, and immune cell activation. Abnormal glycosylation is associated with inflammation, tumors, autoimmunity, and several diseases. Glycan profiles and glycosylation-related enzymes are altered in patients with psoriasis. Specific glycan structures, such as glycosaminoglycans and gangliosides, inhibit the development of psoriasis through various pathways. Lectins are glycan-binding proteins that are widely involved in the pathogenesis of psoriasis. The differential serum, epidermal, and dermal expression of galectins in patients with psoriasis distinguishes psoriasis from other nonspecific psoriasis-like dermatitis. This article summarizes relevant literature on psoriasis-related glycans to help clarify the potential molecular mechanisms of psoriasis and identify novel biomarkers and targets for the treatment of psoriasis.
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