Systematic analysis for clinical characteristics and outcomes of IgG4-related disease patients during the COVID-19 pandemic.

BACKGROUND: To systematically describe clinical characteristics and investigate factors associated with COVID-19-related infection, hospital admission, and IgG4-related disease relapse in IgG4-RD patients. METHODS: Physician-reported IgG4-RD patients were included in this retrospective study. Using multivariable logistic regression analysis to determine factors for primary outcome (COVID-19-related IgG4-RD relapse) and secondary outcome (COVID-19-related infection and hospital admission). Covariates included age, sex, body mass index, smoking status, comorbidities, IgG4-RD clinical features, and treatment strategies. RESULTS: Among 649 patients, 530 had a diagnosis of COVID-19, 25 had COVID-19-related hospital admission, and 69 had COVID-19-related IgG4-RD relapse. Independent factors associated with COVID-19 infection were age (OR, 0.98; 95% CI, 0.96-1.00), body mass index (1.10, 1.03-1.18), and tofacitinib (0.34, 0.14-0.79). Further analysis indicated that age (1.10, 1.03-1.16), coronary heart disease (24.38, 3.33-178.33), COVID-19-related dyspnea (7.11, 1.85-27.34), pulmonary infection (73.63, 16.22-4615.34), and methotrexate (17.15, 1.93-157.79) were associated with a higher risk of COVID-19-related hospital admission. Importantly, age (0.93, 0.89-0.98), male sex (0.16, 0.03-0.80), ever/current smoking (19.23, 3.78-97.80), COVID-19-related headache (2.98, 1.09-8.17) and psychiatric symptoms (3.12, 1.07-9.10), disease activity before COVID-19 (1.89, 1.02-3.51), number of involved organs (1.38, 1.08-1.76), glucocorticoid dosage (1.08, 1.03-1.13), and methotrexate (5.56, 1.40-22.08) were strong factors for COVID-19-related IgG4-RD relapse. CONCLUSIONS: Our data add to evidence that smoking and disease-specific factors (disease activity, number of involved organs, and specific medications) were risk factors of COVID-19-related IgG4-RD relapse. The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate and increasing glucocorticoid dosages in the COVID-19 era. Key Points • COVID-19-related infection or hospital admission were associated with known general factors (age, body mass index, specific comorbidities and methotrexate) among IgG4-RD patients. • Smoking and disease-specific factors (disease activity, number of involved organs and specific medications) were associated with higher odds of COVID-19-related IgG4-RD relapse. • The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate or increasing glucocorticoid dosages.

CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

OBJECTIVES: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. METHODS: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. RESULTS: In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24 h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. CONCLUSIONS: Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

Lycium barbarum polysaccharide alleviates DSS-induced chronic ulcerative colitis by restoring intestinal barrier function and modulating gut microbiota.

PURPOSE: This study examined the protective effects and mechanism of Lycium barbarum polysaccharides (LBP) in the context of intestinal barrier function and intestinal microbiota in mice with dextran sulfate sodium (DSS)-induced chronic ulcerative colitis (UC). METHODS: C57BL/6J male mice were assigned to a standard normal diet without DSS (control group), a normal diet with DSS (DSS group, 2% DSS given discontinuously for 3 weeks) or a normal diet supplemented with LBP (1% dry feed weight, LBP group, 2% DSS given discontinuously for 3 weeks) for a total of 8 weeks, at which point colonic tissues and caecal contents were collected. RESULTS: LBP exerted a significant effect against colitis by increasing body weight, colon length, DAI and histopathological scores. LBP inhibited proinflammatory cytokines (IL-1ß, IL-6, iNOS and TNF-α) expression, improved anti-inflammatory cytokine (IL-10) expression, promoted the expression of tight junction proteins (Occludin and ZO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2) activation and decreased Claudin-2 expression to maintain the intestinal mucosal barrier. In addition, the abundances of some probiotics (Ruminococcaceae, Lactobacillus, Butyricicoccus, and Akkermansia) were decreased with DSS treatment but increased obviously with LBP treatment. And LBP reduced the abundance of conditional pathogens associated with UC (Mucispirillum and Sutterella). Furthermore, LBP improved the production of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid and isobutyric acid. CONCLUSION: LBP can alleviate DSS-induced UC by regulating inflammatory cytokines and tight junction proteins. Moreover, LBP promotes probiotics, suppresses conditional pathogens and increases SCFAs production, showing a strong prebiotic effect.

The spectrum of B cells in the pathogenesis, diagnosis and therapeutic applications of immunoglobulin G4-related disease.

Immunoglobulin G4 (IgG4)-related disease is a chronic fibroinflammatory disease mediated by immune disorders. Given the challenging clinical diagnosis and treatment, knowledge of the pathogenesis of IgG4-related disease is important. The typical elevation of serum IgG4 concentrations and infiltration of IgG4-positive plasma cells in the involved tissues indicate the involvement of B lymphocytes in the pathogenesis of IgG4-related disease. Mass production of autoantibodies reflects abnormal activation of B cells, which causes tissue damage. Circulating plasmablasts are recently discovered markers that correlate with serum IgG4 concentration, the extent of organ involvement and disease activity. B-cell depletion therapy is an emerging curative strategy that can significantly alleviate clinical manifestations and achieve remission in patients with IgG4-related disease. These findings highlight the potential role of B cells in IgG4-related disease. In this review, we discuss the pathogenic impact of B lymphocytes on IgG4-related disease and describe novel therapies targeting B cells.

Detection methods of synchronous colorectal lesions in proximal colon for patients with obstructive colorectal cancer: a literature review.

INTRODUCTION: Colorectal cancer holds a high morbidity and mortality rate. As a common method for colorectal cancer detection, colonoscopy has difficulty in passing through the malignant stenosis in patients with obstructive colorectal cancer, which results in incomplete detection and missed diagnosis. The missed synchronous lesions increase the risk of metachronous cancer. Therefore, detecting proximal synchronous lesions in patients with obstructive colorectal cancer should be appreciated before operation. AREA COVERED: This review evaluates related literature, aiming at providing clinicians with more ideas and attention for detecting proximal synchronous lesions in patients with obstructive colorectal cancer. EXPERT OPINION: In patients with obstructive colorectal cancer, missed diagnosis of lesions proximal to the obstruction may lead to metachronous colorectal cancer. Except for preoperative colonoscopy which is difficult to pass through malignant stenosis, other methods that can evaluate proximal colon segment are critical. This article introduced several preoperative, intraoperative and postoperative measures for synchronous lesions detection. The choice of methods should base on patients' conditions, aiming at a high diagnostic yield and low risk. Early detection and resection of synchronous lesions in the proximal section of malignant obstruction are expected to minimize the risk of metachronous colorectal cancer and even effect follow-up treatment strategy, which deserves the attention of clinicians.