To dissect the mechanisms of anti-TNFα-induced autoimmunity we examined the phenotype and function of B cells from anti-TNFα-treated patients. Levels of Lyn, Syk, SHP-1, tyrosine 348 phospho-Syk (Y348-Syk) and tyrosine phosphorylated (P-Y) proteins were evaluated and B-cell-surface CD20, CD21 and CD5 were also assessed in 29 patients treated with TNF-α blockers. Following treatment, Lyn, but not Syk or SHP-1, significantly increased particularly in patients with spondyloarthropathies. Increased Lyn levels following treatment correlated with increased Lyn activity as evidenced by a 2.9-fold increase of Y348-Syk (a Lyn target). Peripheral B-cells from 56.3% of the patients displayed a tendency towards increased P-Y levels without any BCR-initiated activation during treatment. CD20, but not CD21, significantly increased in patients with rheumatoid arthritis. Circulating CD5+ B-cells were also significantly expanded during treatment. Our findings suggest that B cells in anti-TNFα-treated patients display functional and phenotypical aberrations that may enhance our understanding of TNF-α blocker-induced autoimmunity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.clim.2011.01.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Engineering Resilient CAR T Cells for Immunosuppressive Environment.
Mol Ther
January 2025
Brown Center for Immunotherapy. Indiana University School of Medicine. 975 W. Walnut St., IB554A, Indianapolis, IN 46202. Electronic address:
Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized cancer treatment and is now being explored for other diseases, such as autoimmune disorders. While the tumor microenvironment (TME) in cancer is often immunosuppressive, in autoimmune diseases, the environment is typically inflammatory. Both environments can negatively impact CAR T cell survival: the former through direct suppression, hypoxia, and nutrient deprivation, and the latter through chronic T cell receptor (TCR) engagement, risking exhaustion.
View Article and Find Full Text PDFTissue nanotransfection-based endothelial PLCγ2-targeted epigenetic gene editing in vivo rescues perfusion and diabetic ischemic wound healing.
Mol Ther
January 2025
Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, United States; Department of Surgery, Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address:
Diabetic wounds are complicated by underlying peripheral vasculopathy. Reliance on vascular endothelial growth factor (VEGF) therapy to improve perfusion makes logical sense, yet clinical study outcomes on rescuing diabetic wound vascularization have yielded disappointing results. Our previous work has identified that low endothelial phospholipase Cγ2 (PLCγ2) expression hinders the therapeutic effect of VEGF on the diabetic ischemic limb.
View Article and Find Full Text PDFPharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.
Mol Ther
January 2025
Department of Molecular Medicine, University of Southern Denmark; Odense, 5230, Denmark. Electronic address:
Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.
View Article and Find Full Text PDFA Comprehensive Atlas of AAV Tropism in the Mouse.
Mol Ther
January 2025
Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.
View Article and Find Full Text PDFGITRL enhances cytotoxicity and persistence of CAR-T cells in cancer therapy.
Mol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!