Anti-TNF-α therapy in membranous glomerulonephritis.
Ontology highlight
ABSTRACT:
SUBMITTER: Santoro D
PROVIDER: S-EPMC4432417 | biostudies-literature | 2012 Oct
REPOSITORIES: biostudies-literature
Publications
Anti-TNF-α therapy in membranous glomerulonephritis.
Santoro Domenico D Postorino Adele A Costantino Giuseppe G Savica Vincenzo V Bellinghieri Guido G
Clinical kidney journal 20121001 5
Similar Datasets
Project description:In September 2010, a 75-year-old hepatitis B virus (HBV)-positive man was admitted to our hospital because of fever, persistent cough, general fatigue, and leg edema. The patient was a hepatitis B surface antigen carrier with detectable HBV DNA level. On admission, laboratory examination revealed severe inflammatory signs, decreased serum albumin, and renal insufficiency with proteinuria. The patient had rapidly progressive renal insufficiency without pulmonary involvement over the few days after admission. Renal biopsy showed membranous nephropathy (MN) with crescent formation. Further serological study revealed a high titer of anti-glomerular basement membrane (GBM) antibody, suggestive of anti-GBM glomerulonephritis superimposed on HBV-associated MN. For both preventing HBV reactivation during immunosuppressive therapy and treating HBV-associated MN, the administration of entecavir was immediately initiated, and then treatment with plasma exchange (PE) and intravenous methylprednisolone administration was performed. Both HBV DNA level and an anti-GBM titer became undetectable, and clinical remission of MN was subsequently achieved. This was a rare case of an elderly patient with anti-GBM glomerulonephritis superimposed on HBV-associated MN, who was successfully treated with PE, corticosteroid, and entecavir combination therapy.
| S-EPMC5411555 | biostudies-literature
Project description:BackgroundAnti-tumor necrosis factor-α (TNF-α) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis.MethodsWe conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998-2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using Cox proportional hazards analysis to adjust for baseline propensity scores and time-varying use of glucocorticoids. We also made head-to-head comparisons between anti-TNF-α agents.ResultsAmong the 8417 persons included in the analysis, 38 (0.4%) received a diagnostic code for ILD by the end of follow-up, including 23 of 4200 (0.5%) who used anti-TNF-α during study follow-up, and 15 of 5423 (0.3%) who used only non-biologic therapies. The age-standardized and gender-standardized incidence rate of ILD, per 100 person-years, was 0.21 [95% confidence interval (CI) 0-0.43] for rheumatoid arthritis and appreciably lower for other autoimmune diseases. Compared with the use of non-biologic therapies, use of anti-TNF-α therapy was not associated with a diagnosis of ILD among patients with rheumatoid arthritis (adjusted hazard ratio, 1.03; 95%CI 0.51-2.07), nor did head-to-head comparisons across anti-TNF-α agents suggest important differences in risk, although the number of cases available for analysis was limited.ConclusionThe study provides evidence that compared with non-biologic therapies, anti-TNF-α therapy does not increase the occurrence of ILD among patients with autoimmune diseases and informs research design of future safety studies of ILD.
| S-EPMC3618622 | biostudies-literature
Project description: Not available
| S-EPMC10943853 | biostudies-literature
Project description:PurposeTo compare mortality among patients with selected autoimmune diseases treated with anti-tumor necrosis factor alpha (TNF-α) agents with similar patients treated with non-biologic therapies.MethodsCohort study set within several large health care programs, 1998-2007. Autoimmune disease patients were identified using diagnoses from computerized healthcare data. Use of anti-TNF-α agents and comparison of non-biologic therapies were identified from pharmacy data, and mortality was identified from vital records and other sources. We compared new users of anti-TNF-α agents to new users of non-biologic therapies using propensity scores and Cox proportional hazards analysis to adjust for baseline differences. We also made head-to-head comparisons among anti-TNF-α agents.ResultsAmong the 46 424 persons included in the analysis, 2924 (6.3%) had died by the end of follow-up, including 1754 (6.1%) of the 28 941 with a dispensing of anti-TNF-α agent and 1170 (6.7%) of the 17 483 who used non-biologic treatment alone. Compared to use of non-biologic therapies, use of anti-TNF-α therapy was not associated with an increased mortality in patients with rheumatoid arthritis (adjusted hazard ratio [aHR] 0.93 with 95% confidence intervals (CI) 0.85-1.03); psoriasis, psoriatic arthritis, or ankylosing spondylitis (combined aHR 0.81 with CI 0.61-1.06; or inflammatory bowel disease (aHR 1.12 with CI 0.85-1.46). Mortality rates did not differ to an important degree between patients treated with etanercept, adalimumab, or infliximab.ConclusionAnti-TNF-α therapy was not associated with increased mortality among patients with autoimmune diseases.
| S-EPMC3565563 | biostudies-literature
Project description:A Japanese man in his early 70s was referred to our hospital because of massive proteinuria. Analysis of his kidney biopsy demonstrated glomerular subepithelial immune deposits containing immunoglobulin (Ig)G, which was dominant for the IgG1 subclass. Immunoperoxidase staining for neural epidermal growth factor-like 1 protein (NELL1) was positive on the glomerular capillary walls, whereas neither serum anti-phospholipase A2 receptor (PLA2R) antibodies nor immunofluorescence staining for PLA2R was positive. Detailed investigation revealed no associated conditions, including underlying malignancies, and thus he was diagnosed as having NELL1-associated idiopathic membranous nephropathy (MN). The patient was treated with steroids, which substantially improved his nephrotic syndrome. Interestingly, serum anti-NELL1 as well as anti-PLA2R antibodies became positive during his clinical course. Serology-based approaches are currently proposed for the treatment of patients suspected of having MN; however, an accurate diagnosis of the present patient would have been difficult if such an approach was performed only at a later phase of the disease. Several target antigens for the glomerular immune deposits observed in patients with MN have recently been identified, and dual positivity of antibodies to these antigens reportedly occurs in some patients. Further accumulation and analyses of such patients are needed to establish more appropriate diagnostic approaches for MN.
| S-EPMC10131105 | biostudies-literature
Project description:Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.
| S-EPMC9963154 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.
| S-EPMC7566733 | biostudies-literature
Project description:BackgroundMembranous glomerulonephritis (MGN) is a common kidney disease. Despite many evidences support that many immune and inflammation-related genes could serve as effective biomarkers and treatment targets for MGN patients, the potential associations among MGN-, immune- and inflammation-related genes have not been sufficiently understood.MethodsHere, a global immune-, inflammation- and MGN-associated triplets (IIMATs) network is constructed and analyzed. An integrated and computational approach is developed to identify dysregulated IIMATs for MGN patients based on expression and interaction data.Results45 dysregulated IIMATs are identified in MGN by above method. Dysregulated patterns of these dysregulated IIMATs are complex and various. We identify four core clusters from dysregulated IIMATs network and some of these clusters could distinguish MGN and normal samples. Specially, some anti-cancer drugs including Tamoxifen, Bosutinib, Ponatinib and Nintedanib could become candidate drugs for MGN based on drug repurposing strategy follow IIMATs. Functional analysis shows these dysregulated IIMATs are associated with some key functions and chemokine signaling pathway.ConclusionsThe present study explored the associations among immune, inflammation and MGN. Some effective candidate drugs for MGN were identified based on immune and inflammation. Overall, these comprehensive results provide novel insights into the mechanisms and treatment of MGN.
| S-EPMC6947948 | biostudies-literature
Project description:Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.
| S-EPMC9997925 | biostudies-literature
Project description:Crohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract. We performed a whole-genome transcriptional analysis using colonic biopsies from CD patients before and after anti-TNF-α therapy. Involved colonic samples from Crohn's disease patients and healthy colonic samples from non-inflammatory controls were collected for RNA extraction and hybridization on Affymetrix microarrays. Inclusion criteria for CD patients were: age between 18 and 70, diagnosis of CD established at least 4 months before inclusion and exclusion of concomitant infection. Active disease was defined by endoscopic and clinical score: endoscopic active disease was defined as a CD endoscopic index of severity (CDEIS) of 5 or more and the presence of large ulcers (> 0.5 cm diameter) in at least one of the explored segments. Clinical activity was defined as a CD activity index (CDAI) above 150. Finally, a total of 39 biopsies were analyzed: 17 healthy controls, 10 active CD without anti-TNF therapy, 5 active CD with anti-TNF therapy (non-responders) and 7 inactive CD with anti-TNF therapy (responders).
2014-04-08 | E-GEOD-52746 | biostudies-arrayexpress