Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prior studies have demonstrated that treatment of young, prenephritic lupus-prone mice with Ab directed against CD40 ligand (CD40L) prolongs survival and decreases the incidence of severe nephritis. In this report, we show that for (SWR x NZB)F1 (SNF1) animals with established lupus nephritis, long-term treatment with anti-CD40L beginning at either 5.5 or 7 mo of age prolonged survival and decreased the incidence of severe nephritis. "Older" mice were chosen for these studies to more closely resemble the clinical presentation of patients with established renal disease. We show that age at the start of treatment, which typically correlates with severity of disease, is an important factor when determining an efficacious therapeutic protocol since animals that began treatment at 7 mo of age required a more aggressive treatment protocol than animals at 5.5 mo of age. Remarkably, several anti-CD40L-treated animals beginning treatment at age 5.5 mo demonstrated a decline in proteinuria, as opposed to increasing proteinuria levels seen in hamster IgG (HIg)-treated controls, and histologic examination of kidneys from anti-CD40L-treated mice revealed dramatically diminished inflammation, sclerosis/fibrosis, and vasculitis, in marked contrast to the massive inflammation and kidney destruction observed in control animals that received hamster IgG. Spleens from anti-CD40L-treated mice also exhibited markedly reduced inflammation and fibrosis compared with controls. Together, these results show that treatment of older, nephritic SNF1 animals with long-term anti-CD40L immunotherapy significantly prolongs survival, reduces the severity of nephritis, and diminishes associated inflammation, vasculitis, and fibrosis.
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PMID:Anti-CD40 ligand antibody treatment of SNF1 mice with established nephritis: preservation of kidney function. 949 53

Kawasaki disease (KD) is an acute systemic vasculitis syndrome of infants and young children. Although its etiology is largely unknown, epidemiological findings suggest that genetic factors play a role in the pathogenesis of KD. To identify genetic factors, affected sib-pair analysis has been performed. One of the identified peaks was located on the Xq26 region. A recent report of elevated expression of CD40 ligand (CD40L), which maps to Xq26, during the acute-phase KD, and its relationship to the development of coronary artery lesions (CAL) prompted us to screen for polymorphism of CD40L and to study the association of the gene to KD. A newly identified SNP in intron 4 (IVS4+121 A>G) is marginally over-represented in KD patients as compared to controls (109/602, 18.1 vs 111/737, 15.1%). When male KD patients with CAL were analyzed as a patient group, the SNP was significantly more frequent than in controls (15/58, 25.9%, vs 111/737, 15.1%, OR=2.0, 95% CI=1.07-3.66; P=0.030). Interestingly, this variation was extremely rare in a control Caucasian population (1/145, 0.7%). Our results suggest a role of CD40L in the pathogenesis of CAL and might explain the excess of males affected with KD.
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PMID:CD40 ligand gene and Kawasaki disease. 1536 12

Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is B cell-dependent, although how particular B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype remains controversial, regulatory B cells (Bregs ), play a role in immunological tolerance via interleukin (IL)-10. Putative CD19(+) CD24(hi) CD38(hi) and CD19(+) CD24(hi) CD27(+) Bregs were evaluated in addition to their CD5(+) subsets in 69 patients with ANCA-associated vasculitis (AAV). B cell IL-10 was verified by flow cytometry following culture with CD40 ligand and cytosine-phosphate-guanosine (CpG) DNA. Patients with active disease had decreased levels of CD5(+) CD24(hi) CD38(hi) B cells and IL-10(+) B cells compared to patients in remission and healthy controls (HCs). As IL-10(+) and CD5(+) CD24(hi) CD38(hi) B cells normalized in remission within an individual, ANCA titres decreased. The CD5(+) subset of CD24(hi) CD38(hi) B cells decreases in active disease and rebounds during remission similarly to IL-10-producing B cells. Moreover, CD5(+) B cells are enriched in the ability to produce IL-10 compared to CD5(neg) B cells. Together these results suggest that CD5 may identify functional IL-10-producing Bregs . The malfunction of Bregs during active disease due to reduced IL-10 expression may thus permit ANCA production.
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PMID:Reduced CD5(+) CD24(hi) CD38(hi) and interleukin-10(+) regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies. 2537 52

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that results from massive expansion of polyclonal IgG4-switched B and/or plasma cells. It can virtually affect all organs and its diagnosis relies on clinical, serological and histopathological criteria. The role of autoimmunity and adaptive immune system in IgG4-RD is reflected in plasmablast differentiation, germinal center formation and IgG4 production induced by CD4+ cells expressing CD40 ligand. IgG4-RD has been considered to be a Th2/Treg-driven disorder, but follicular helper T cells are important in driving the IgG subclass switch. Prompt clinical responses to rituximab, human leukocyte antigen (HLA) associations and the presence of autoantibodies also point to the importance of adaptive immune system. However, innate immunity may induce storiform fibrosis through T-cell independent responses as a consequence of toll-like receptors activation by microbe-and damage-associated molecular patterns, while macrophages and basophils also appear to have a significant role in IgG4-RD pathogenesis. Allergic mechanisms may drive IgG4-RD, but only a subgroup has elevated IgE serum levels and peripheral eosinophilia. Finally, the 2012 revised Chapel Hill Consensus Conference nomenclature pointed IgG4-RD as a cause of large-vessel vasculitis. This review aims to discuss how to place IgG4-RD in the spectrum of immune-mediated and rheumatologic disorders.
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PMID:IgG4-related disease: How to place it in the spectrum of immune-mediated and rheumatologic disorders? 3185 51