DeCure for Immunodeficiency 113 with autoimmunity and autoinflammation
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 113 with autoimmunity and autoinflammation — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleImmunodeficiency 113 with autoimmunity and autoinflammation maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for immunodeficiency 113 with autoimmunity and autoinflammation is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
actin related protein 2/3 complex subunit 5 (ARPC5) — ARPC5 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6UHC · 3.9 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2016 retrospective study of 30 genetically diagnosed primary immunodeficiency patients with autoimmunity, the mean age at first symptoms was 8.96 months and mean age at genetic diagnosis was 82.55 months. Twelve patients (40%) had autoimmunity at first presentation. The most common autoimmune findings were inflammatory bowel disease or IBD-like findings (14 patients, 46.7%), immune thrombocytopenic purpura (11 patients, 36.7%), and autoimmune hemolytic anaemia (9 patients, 30.0%). Fifteen patients (50%) responded to immunosuppressive agents. Ten patients underwent haematopoietic stem cell transplantation. Six patients were lost to follow-up due to complications.
A 2002 review notes that primary immunodeficiency diseases are associated with troublesome and sometimes life-threatening autoimmune complications, and that understanding the molecular basis of these conditions has led to more focused treatment. A 2021 review states that systemic immunodeficiency disorders are heterogeneous and that many patients are diagnosed late, suffering from chronic infections, end-organ damage, or death before diagnosis. It adds that ideal diagnosis and suitable treatment remain key to successful management.
No drug is tested or recommended in any of these abstracts. No survival or response rates beyond the 50% immunosuppressive response in the 2016 cohort are reported. The 2016 study does not specify which immunosuppressive agents were used, nor does it report long-term outcomes for the transplanted patients beyond noting six lost to follow-up.
What is still missing is a prospective trial designed to test any specific drug in a defined genetic subgroup of immunodeficiency with autoimmunity. The 2016 study is retrospective and small. No randomised controlled trial exists. Patient stratification by genetic mutation is possible but not yet linked to a tested therapy. Funding for such a trial, and a clear regulatory path for a repurposed drug, are absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 2002 · 182 citations · open access
Autoimmunity in human primary immunodeficiency diseases
AbstractHuman primary immunodeficiency diseases are experiments of nature characterized by an increased susceptibility to infection. In many cases, they are also associated with troublesome and sometimes life-threatening autoimmune complications. In the past few years, great strides have been made in understanding the molecular basis of primary immunodeficiencies, and this had led to more focused and successful treatment. This review has 3 aims: (1) to highlight the variety of autoimmune phenomena associated with human primary immunodeficiency diseases; (2) to explore how primary immunodeficiencies predispose patients to autoimmune phenomena triggered by opportunistic infections; and (3) to consider the rationale for the current treatment strategies for autoimmune phenomena, specifically in relation to primary immunodeficiency diseases. Reviewing recent advances in our understanding of the small subgroup of patients with defined causes for their autoimmunity may lead to the development of more effective treatment strategies for idiopathic human autoimmune diseases.
Current Opinion in Rheumatology · 2008 · 71 citations · open access
Rheumatologic and autoimmune manifestations of primary immunodeficiency disorders
AbstractPURPOSE OF REVIEW: Although it may seem paradoxical, primary immunodeficiency disorders are frequently complicated by autoimmune and inflammatory conditions. These conditions pose significant diagnostic and therapeutic challenges for clinicians caring for these patients. There have been a number of new insights into how immunodeficiencies can predispose to autoimmunity, and rheumatologists should understand the basis for and manifestations of autoimmunity in primary immunodeficiency disorders to more effectively care for these patients. RECENT FINDINGS: A number of mechanisms have recently been found to link primary immunodeficiencies and autoimmunity, including increased homeostatic proliferation in primary immunodeficiencies associated with lymphopenia and defects in regulatory T cells in the Wiskott-Aldrich syndrome. Primary immunodeficiencies that affect the innate immune system can also lead to inappropriate inflammation through impairing negative regulatory mechanisms in innate immune cells. SUMMARY: The realization that primary immunodeficiencies can also impair negative regulation of immune responses has provided a new framework for the understanding of autoimmunity associated with these conditions. These insights may lead to new, more targeted therapies for autoimmune complications in primary immunodeficiency patients.
Türk Pediatri Arşivi · 2016 · 11 citations · open access
The plethora, clinical manifestations and treatment options of autoimmunity in patients with primary immunodeficiency
AbstractAIM: Although the association between primary immunodeficiency and autoimmunity is already well-known, it has once again become a topic of debate with the discovery of newly-defined immunodeficiencies. Thus, investigation of the mechanisms of development of autoimmunity in primary immunodefficiency and new target-specific therapeutic options has come to the fore. In this study, we aimed to examine the clinical findings of autoimmunity, autoimmunity varieties, and treatment responses in patients who were genetically diagnosed as having primary immunodeficiency. MATERIAL AND METHODS: The files of patients with primary immunodeficiency who had clinical findings of autoimmunity, who were diagnosed genetically, and followed up in our clinic were investigated. The demographic and clinical features of the patients and their medical treatments were evaluated. RESULTS: Findings of autoimmunity were found in 30 patients whose genetic mutations were identified. The mean age at the time of the first symptoms was 8.96±14.64 months, and the mean age of receiving a genetic diagnosis was 82.55±84.71 months. The most common diseases showing findings of autoimmunity included immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome (16.7%); autoimmune lymphoproliferative syndrome (10%); lipopolysaccharide-responsive beige-like anchor protein deficiency (10%); and DiGeorge syndrome (10%). Twelve (40%) patients showed findings of autoimmunity at the time of first presentation. The most common findings of autoimmunity included inflammatory bowel disease, inflammatory bowel disease-like findings (n=14, 46.7%), immune thrombocytopenic purpura (n=11, 36.7%), and autoimmune hemolytic anemia (n=9, 30.0%). A response to immunosupressive agents was observed in 15 (50%) patients. Ten patients underwent hematopoietic stem cell transplantation. Six patients were lost to follow-up due to a variety of complications. CONCLUSION: Autoimmunity is frequently observed in patients with primary immunodeficiency. The possibility of primary immunodeficiency should be considered in patients with early-onset manifestations of autoimmunity, and these patients should be carefully monitored in terms of immunodeficiency development. Early diagnosis of primary immunodeficiency may provide favorable outcomes in terms of survival.
Journal of Pharmaceutical Research International · 2021 · 0 citations · open access
Mechanism of Common Systemic Immunodeficiency Disorders and its Literature Comparison
AbstractSystemic immunodeficiency disorders are heterogenous groups ofImmunodeficiency disorders could experience an assortment of clinical signs, including intermittent, extreme, or irregular diseases, autoimmunity, and lymphoproliferative/malignancies. Immunodeficiency involves an enormous amount of sicknesses, influencing the advancement of the immune system, its function, or both. There is a increase in percentage of immunodeficiency disorders among population. However, numerous patients are diagnosed late; numerous cases experience the ill effects of difficulties by chronic infections, end-organ damage, or even demise before the diagnosis is made. Ideal determination and suitable treatment remain key to the successful management of patients. The objective of this review is to overview the various systemic immunodeficiency disorders and their mechanism of occurrence of immunodeficiency.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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