ArticleNature immunology2019
SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2.
Article in Nature immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- A guide to B cell metabolism.Nature reviews. Immunology · 2026Review
- TCR γδ cell-specific STAT5 gain of function induces a druggable chronic human immune dysregulation.Journal of human immunity · 2026Article
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- MPPMolecular biology reports · 2025Article
- circRNA-79530 regulates Twist-mediated mitochondrial damageEuropean journal of histochemistry : EJH · 2025Article
- ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion.Nature cell biology · 2025Article
- Unveiling the hidden role of SDHA in breast cancer proliferation: a novel therapeutic avenue.Cancer cell international · 2025Article
- Transcriptional dynamics in type 2 diabetes progression is linked with circadian, thermogenic, and cellular stress in human adipose tissue.Communications biology · 2025Article
- Interplay between the Redox System and Renal Tubular Transport.Antioxidants (Basel, Switzerland) · 2024Review
- Metabolic profiling of single cells by exploiting NADH and FAD fluorescence via flow cytometry.Molecular metabolism · 2024Article
- Metabolic rewiring and communication in cancer immunity.Cell chemical biology · 2024Review
- Tricarboxylic acid cycle metabolites: new players in macrophage.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Post-transplant Inflammatory Bowel Disease Associated with Donor-Derived TIM-3 Deficiency.Journal of clinical immunology · 2024Article
- The immunometabolic ecosystem in cancer.Nature immunology · 2023Review
- Immunologic and Genetic Contributors to CD46-Dependent Immune Dysregulation.Journal of clinical immunology · 2023Article
- Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.Cell reports. Medicine · 2023Article
- Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure.Gut and liver · 2023Article
- Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023Review
- The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer's Disease Reveals New Insights for AD Study.International journal of molecular sciences · 2023Article
- Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency.The Journal of allergy and clinical immunology · 2023Article
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Authors and funding
33 authors at 13 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Whether screening the metabolic activity of immune cells facilitates discovery of molecular pathology remains unknown. Here we prospectively screened the extracellular acidification rate as a measure of glycolysis and the oxygen consumption rate as a measure of mitochondrial respiration in B cells from patients with primary antibody deficiency. The highest oxygen consumption rate values were detected in three study participants with persistent polyclonal B cell lymphocytosis (PPBL). Exome sequencing identified germline mutations in SDHA, which encodes succinate dehydrogenase subunit A, in all three patients with PPBL. SDHA gain-of-function led to an accumulation of fumarate in PPBL B cells, which engaged the KEAP1-Nrf2 system to drive the transcription of genes encoding inflammatory cytokines. In a single patient trial, blocking the activity of the cytokine interleukin-6 in vivo prevented systemic inflammation and ameliorated clinical disease. Overall, our study has identified pathological mitochondrial retrograde signaling as a disease modifier in primary antibody deficiency.
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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.