SAMHD1 Research Digest — 2026-09-06¶
Generated by samhd1_monitor | Model: claude-sonnet-5
Summary: 13 papers evaluated | 2 high-relevance (≥7) | 6 medium (5–6) | 5 low (3–4) | 0 scored <3
🔴 High Relevance (Score 7–10)¶
Auto-added to Zotero (threshold ≥6)
The mitochondrial RNA extrusion-induced innate immunity is regulated by N6-methyladenosine machinery (from RNA epigenetics/molecular virology)
Hu Qing; Zhang Yifei; Wang Shixuan; Zeng Xueping; Wang Fengyu — preprint (preprint) 2026
Score: 7/10 | Pathways: VDAC1, cGAS-STING, NLRP3, treatment-target
This paper details VDAC1-mediated mitochondrial nucleic acid (mtRNA) extrusion activating cytosolic PRRs (RIG-I/MDA5/TLR/PKR), directly extending the BLUE-loop VDAC1-macropore mechanism central to SAMHD1 A565T interferon pathology beyond mtDNA to mtRNA, with m6A machinery as a novel druggable node.
DOI: 10.64898/2026.08.27.747681
Neonatal Aicardi-Goutières syndrome presenting with macrophage activation syndrome-like hyperinflammation and severe congenital glaucoma: a case report. (from pediatric rheumatology/neonatology and ophthalmology)
Konak Murat; Bozkurt Banu; Ceylaner Gülay; Cüceoğlu Müşerref Kasap; Özdemir Fati — Pediatric rheumatology online journal 2026
Score: 7/10 | Pathways: AGS-spectrum, JAK-STAT, treatment-target, clinical-phenotype
AGS type 2 case with type I interferonopathy responding to JAK1/2 inhibitor (ruxolitinib) directly parallels the SAMHD1 interferonopathy spectrum, MAS-like hyperinflammation, and glaucoma phenotype tracked in the family, plus congenital glaucoma overlaps with a listed family phenotype.
DOI: 10.1186/s12969-026-01264-x
🟡 Medium Relevance (Score 5–6)¶
Score ≥6 auto-added to Zotero; lower scores: review manually
Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure. (from cardiology/aging biology)
Bubb Kristina; Rigoni Giovanni; Papadea Polyxeni; Pironti Gianluigi; Misic Jelen — Science advances 2026
Score: 6/10 | Pathways: POLG-mtDNA, mito-ROS-NF-kB, clinical-phenotype
Demonstrates that cardiomyocyte-intrinsic POLG-driven mtDNA mutations trigger an immune/antigen-presentation response and progressive heart failure, paralleling the PURPLE-stream POLG stalling→ox-mtDNA→immune activation mechanism and supporting cardiac relevance of mitochondrial-immune crosstalk in the SAMHD1 model.
DOI: 10.1126/sciadv.aec8606
Beyond genes: EpiSwitch® and Orion platform-powered 3D genome architecture biomarkers reveal shared biology across ME/CFS, long COVID, PTSD, rheumatoid arthritis, and multiple sclerosis. (from systems genomics/epigenetics (3D chromatin architecture biomarker platform) applied across rheumatology, neurology, and post-viral fatigue syndromes)
Hunter Ewan; Alshaker Heba; Vugrinec Dominik; Bautista Shekinah; Gebregzabhar Ab — Journal of translational medicine 2026
Score: 6/10 | Pathways: ME-CFS, cGAS-STING, mTOR-lysosomal, JAK-STAT, clinical-phenotype
This paper identifies shared immune/interferon/mitochondrial/mTOR pathway convergence across ME/CFS, long COVID, RA, and MS using 3D genomic architecture analysis, directly relevant to the proband's ME/CFS phenotype and the family's autoimmune/interferonopathy features (RA tracked in family phenotypes) even though SAMHD1 is not mentioned.
DOI: 10.1186/s12967-026-08874-9
Modulatory effects of methyl gallate on the inflammatory response in gout arthritis via P2X7 receptor. (from Pharmacology/Rheumatology)
Pereira Felipe M S; Correa Luana B; Seito Leonardo N; Ranke Natalia L VON; Mende — Anais da Academia Brasileira de Ciencias 2026
Score: 6/10 | Pathways: NLRP3, urate-NLRP3, treatment-target
This paper directly addresses the GOLD pathway (dGTP→purine catabolism→uric acid→MSU crystals→NLRP3) via P2X7-mediated MSU/NLRP3 activation and IL-1β release, offering a treatment target relevant to the gout phenotype tracked in the family.
DOI: 10.1590/0001-3765202620250722
Mitochondrial immunometabolism in sepsis: bridging immune cell dysfunction and organ failure. (from Critical care/sepsis immunometabolism)
Zhang Xingzhan; Zhao Ling; Fu Wei; Pan Lili; Wu Huanhuan — Frontiers in immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, treatment-target
Reviews mtDNA/mtROS/cardiolipin-driven cGAS-STING and NLRP3 activation as core drivers of sepsis organ failure, mechanistically overlapping with the SAMHD1 A565T ox-mtDNA→cGAS-STING/NLRP3 loops even though SAMHD1 itself is not mentioned.
DOI: 10.3389/fimmu.2026.1921226
Leptin attenuates heat stress-induced mitoxyperilysis in porcine Sertoli cells by suppressing the mtDNA-cGAS-STING axis. (from veterinary reproductive biology/animal science)
Guo Ming; Zhang Jinyang; Gu Shanshan; Gao Yawen; Zhu Zhendong — Journal of animal science and biotechnology 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NF-kB-IKK, mito-ROS-NF-kB, treatment-target
Demonstrates VDAC1-mediated mtDNA leakage activating cGAS-STING-TBK1-IRF3/NF-κB axis and inflammatory cytokine production, directly paralleling the BLUE pathway mechanism in the SAMHD1 model, with leptin as a novel mitochondrial-protective therapeutic modulator of this axis.
DOI: 10.1186/s40104-026-01489-6
Gut microbiota–mitochondria–barrier–multiorgan axis: a network-based hypothesis for systemic injury (from Gastroenterology/Critical Care Medicine)
Yachao Li; Huai-Jue Qiu; Xiang Gao; Yanling Zhang; Qin Xia — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, mito-ROS-NF-kB, clinical-phenotype
Describes mtDNA/mtDAMP-driven cGAS-STING and NLRP3 activation as a mechanistic hub linking mitochondrial dysfunction to systemic inflammation, paralleling the SAMHD1-driven Loop A/B mitochondrial-innate immune convergence though in a gut-microbiota context rather than SAMHD1 pathway directly.
DOI: 10.3389/fimmu.2026.1885379
🟢 Low Relevance (Score 3–4)¶
Potential specialty bridges — skim titles
Quantitative adaptor heterogeneity sets single-cell thresholds for innate immune activation and attenuation (from single-cell biophysics/systems immunology)
Dey Arpan; Cui Yuhao; Nawalpuri Bharti; Meisl Georg; Sewell Gavin — preprint (preprint) 2026
Score: 4/10 | Pathways: NF-kB-IKK, other
This paper studies MyD88/TLR-driven NF-κB signaling heterogeneity in macrophages, tangential to the SAMHD1-cGAS-STING-NLRP3-NF-κB interferonopathy axis but not directly connected to SAMHD1, dNTP metabolism, or mitochondrial pathology.
DOI: 10.21203/rs.3.rs-10682444/v1
Mutant p53 Gain-of-Function and Immune Suppression: Mathematical Modeling of STING-TBK1-IRF3 Axis Restoration for Enhanced Cancer Therapy. (from computational oncology/mathematical biology)
Omer Salaheldin; Ouifki Rachid; Mambili-Mamboundou Hermane — Mathematical biosciences 2026
Score: 4/10 | Pathways: cGAS-STING
This is a mathematical modeling paper about mutant p53 suppression of the STING-TBK1-IRF3 axis in cancer immune evasion, touching the same IFN-I signaling node relevant to SAMHD1 biology but with no connection to SAMHD1, dNTP metabolism, or the family phenotype.
DOI: 10.1016/j.mbs.2026.109806
NLRP3 Inflammasome Activation and Atherogenic Lipid Profile in Hemodialysis Patients. (from Nephrology/dialysis)
Abdelaziz Mohammed N; Elshabrawy Nehal; Almenshawy Ahmed; Elsodany Karim A; Elka — Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 2026
Score: 3/10 | Pathways: NLRP3
Studies NLRP3 inflammasome and lipid atherogenicity in hemodialysis patients without any SAMHD1, interferon, or mitochondrial dNTP connection, only tangentially touching the NLRP3 node in this framework.
DOI: 10.1002/1744-9987.70158
Precision genome editing strategies for enduring lipid lowering in atherosclerosis. (from Cardiology/lipidology gene therapy)
Chowdhury Durlav; Singh Nirdesh; Garai Swarnalata; Pandey Devi Prasad; Bodakhe S — European journal of pharmacology 2026
Score: 3/10 | Pathways: prime-editing, gene-therapy-delivery
Reviews precision genome editing (CRISPR, base/prime editing, AAV/LNP delivery) for lipid-lowering in atherosclerosis, offering only generic technology overlap with gene therapy correction strategies but no SAMHD1, interferonopathy, or mitochondrial pathway relevance.
DOI: 10.1016/j.ejphar.2026.179312
NIR-II Small-Molecule Shuttle-Like Nanoassemblies for Mild-Temperature NIR-II Photothermal Enhanced Cuproptosis/STING Activation and Cancer Immunotherapy. (from oncology nanomedicine/photothermal therapy)
Dong Xue; Zhu Junfan; Sun Ying; Li Nianshu; Dai Shipeng — 2026
Score: 3/10 | Pathways: cGAS-STING, VDAC1
This is a cancer nanomedicine paper using mtDNA-release/cGAS-STING activation as an immunotherapy mechanism in tumors, unrelated to SAMHD1 haploinsufficiency but tangentially touching the same downstream cGAS-STING/mtDNA-release pathway.
DOI: 10.1002/smll.75620
Pathway Coverage This Week¶
cGAS-STING: 7 papersNLRP3: 5 paperstreatment-target: 5 papersclinical-phenotype: 4 papersmito-ROS-NF-kB: 4 papersVDAC1: 3 papersJAK-STAT: 2 papersNF-kB-IKK: 2 papersAGS-spectrum: 1 papersPOLG-mtDNA: 1 papersME-CFS: 1 papersmTOR-lysosomal: 1 papersurate-NLRP3: 1 papersother: 1 papersprime-editing: 1 papersgene-therapy-delivery: 1 papers