ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Bcl-2 as a Therapeutic Target in Human Tubulointerstitial Inflammation.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Unlocking the Neuroprotective Potential ofAntioxidants (Basel, Switzerland) · 2026Review
- The Pathogenesis, Potential Biomarkers and Novel Therapeutic Strategies for Tubulointerstitial Nephritis in Systemic Lupus Erythematosus-A Narrative Review.International journal of molecular sciences · 2025Review
- Apoptosis in post-streptococcal glomerulonephritis and mechanisms for failed of inflammation resolution.Pediatric nephrology (Berlin, Germany) · 2024Review
- Spatial proteomics landscape and immune signature analysis of renal sample of lupus nephritis based on laser-captured microsection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Case Report: Rapid renal response to venetoclax monotherapy in a CLL patient with secondary membranous glomerulonephritis.Frontiers in oncology · 2023Article
- Ferroptosis of CD163Frontiers in immunology · 2023Article
- Interstitial Inflammation in the ISN/RPS 2018 Classification of Lupus Nephritis Predicts Renal Outcomes and is Associated With Bcl-2 Expression.Journal of rheumatic diseases · 2022Article
- Specific in situ inflammatory states associate with progression to renal failure in lupus nephritis.The Journal of clinical investigation · 2022Article
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection.Nature communications · 2021Article
- Quantifying the effects of biopsy fixation and staining panel design on automatic instance segmentation of immune cells in human lupus nephritis.Journal of biomedical optics · 2021Article
- Anti-vimentin antibodies: a unique antibody class associated with therapy-resistant lupus nephritis.Lupus · 2020Article
- Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis.Science translational medicine · 2020Article
- Exposure-Response Analyses of the Effects of Venetoclax, a Selective BCL-2 Inhibitor, on B-Lymphocyte and Total Lymphocyte Counts in Women with Systemic Lupus Erythematosus.Clinical pharmacokinetics · 2020Article
- Development of Murine Systemic Lupus Erythematosus in the Absence of BAFF.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- Contribution of poly(ADP-ribose)polymerase-1 activation and apoptosis in trichloroethene-mediated autoimmunity.Toxicology and applied pharmacology · 2019Article
- The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis.Clinical immunology (Orlando, Fla.) · 2017Review
- Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax.Cancer discovery · 2017Review
- Redefining lupus nephritis: clinical implications of pathophysiologic subtypes.Nature reviews. Nephrology · 2017Review
- Lupus nephritis: Targeting Bcl-2 prevents nephritis in mice.Nature reviews. Rheumatology · 2016Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveIn lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ adaptive immune cell networks that amplify local tissue damage. Since conventional therapy appears ineffective for severe TII, and these patients often progress to renal failure, understanding in situ mechanisms might reveal new therapeutic targets. This study was undertaken to assess whether dysregulated apoptotic regulators maintain local adaptive immunity and drive inflammation in TII.
methodsThis study utilized novel computational approaches that, when applied to multicolor confocal images, quantified apoptotic regulator protein expression in selected lymphocyte subsets. This approach was validated using laser-capture microdissection (LCM) coupled to quantitative polymerase chain reaction (qPCR). Furthermore, the consequences of dysregulated apoptotic mediator expression were explored in a murine model of lupus nephritis.
resultsAnalyses of renal biopsy tissue from patients with lupus nephritis and those with mixed cellular renal allograft rejection revealed that the B cell lymphoma 2 protein (Bcl-2) was frequently expressed in infiltrating lymphocytes, whereas expression of myeloid cell leukemia 1 was low. In contrast, the reciprocal pattern of expression was observed in tonsil germinal centers. These results were consistent with RNA expression data obtained using LCM and qPCR. Bcl-2 was also highly expressed in tubulointerstitial infiltrates in (NZB × NZW)F1 (NZB/NZW) mice. Furthermore, treatment of NZB/NZW mice with ABT-199, a selective oral inhibitor of Bcl-2, prolonged survival and prevented proteinuria and development of TII in a lupus prevention model. Interestingly, glomerular immune complexes were partially ameliorated by ABT-199 treatment, and serum anti-double-stranded DNA antibody titers were unaffected.
conclusionThese data demonstrate that Bcl-2 is an attractive therapeutic target in patients with lupus nephritis who manifest TII.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.