DeCure for Immunodeficiency 97 with autoinflammation
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 97 with 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 97 with 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 97 with 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
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) — PIK3CG 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…
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RCSB Protein Data Bank · entry 6AUD · 2.015 Å · ligand 10-[(S)-(1-tert-butylpiperidin-4-yl)sulfinyl]-2-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine (BWY). Experimental structure, not a prediction.
What the evidence adds up to
Primary immunodeficiency disorders, including those with autoinflammation, are frequently complicated by autoimmune and inflammatory conditions, which pose diagnostic and therapeutic challenges. A 2008 review notes that mechanisms linking immunodeficiency to autoimmunity include increased homeostatic proliferation in lymphopenic states and defects in regulatory T cells, as seen in Wiskott-Aldrich syndrome. Defects in the innate immune system can also impair negative regulatory mechanisms, leading to inappropriate inflammation. The review suggests that understanding these pathways may lead to more targeted therapies for autoimmune complications, but provides no specific treatment data.
A 2024 review describes autoinflammatory disease (AID) as a spectrum of disorders with recurrent sterile inflammation. By 2022, the International Union of Immunological Societies had documented 485 inborn errors of immunity, many with autoinflammatory features. The review notes that AIDs range from common gout to ultrarare monogenic diseases, can present in adulthood or the elderly, and are clinically challenging due to rarity and heterogeneity. It offers an approach to clinical assessment and management but does not report any trial results, survival rates, or response rates for any specific drug.
A 2021 review states that primary immunodeficiency diseases (PIDs) are genetically determined and collectively affect between 1 in 1,000 and 1 in 5,000 people worldwide. Clinical manifestations include susceptibility to infection, autoimmunity, and bone marrow failure. The review emphasises that identifying genetic mechanisms can dictate targeted therapies or haematopoietic stem cell transplantation, but again provides no concrete numbers on outcomes for any drug or intervention in immunodeficiency 97 with autoinflammation.
No abstract reports any clinical trial, survival data, or response rates for any drug specifically in immunodeficiency 97 with autoinflammation. What is missing is any dedicated trial funding, a defined patient stratification strategy for this ultrarare condition, and prospective data on whether targeted therapies or transplantation improve outcomes in this specific genetic disorder.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Significance of Interferon-γ Neutralizing Autoantibodies Against Disseminated Nontuberculous Mycobacterial Disease
AbstractBackground: Interferon-γ neutralizing autoantibodies (nIFNγ-autoAbs) are reported in patients with disseminated nontuberculous mycobacteria (NTM) infection and may function by increasing the infection risk. Notwithstanding, the prevalence of nIFNγ-autoAbs as well as the clinical presentation, diagnosis, and natural history of disseminated NTM infection in these patients is poorly understood. Methods: In this retrospective observational study, data and sera for 331 Japanese subjects with mycobacterial infection were collected and analyzed. IFNγ-autoAb titers in sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry. Results: Disseminated NTM was identified in 50 human immunodeficiency virus-uninfected patients. Of these, 30 of 37 (81%) immunocompetent patients had an increased nIFNγ-autoAb titer whereas only 1 of 13 (7.7%) immunodeficient patients had an increased nIFNγ-autoAb titer (P < .0001, χ2 test). Presenting symptoms were nonspecific and NTM infection was not included in the differential diagnosis in most cases. All patients with disseminated NTM and an increased serum nIFNγ-autoAb level received prolonged antimicrobial therapy. In 6 cases when antibiotic treatment was discontinued, NTM infection recurred and required resumption of antibiotic therapy for infection control. The mortality rate was 3.2% in disseminated NTM patients with nIFNγ-autoAbs and 21% in those without. Conclusions: nIFNγ-autoAbs were present in most patients with disseminated NTM infection without a diagnosis of clinical immunodeficiency. Diagnosis of disseminated NTM requires a high degree of suspicion and can be improved by measuring serum nIFNγ-autoAb titer. Long-term antibiotic therapy helps prevent recrudescent NTM infection.
Expert Review of Clinical Immunology · 2016 · 77 citations
Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management
AbstractINTRODUCTION: Common variable immunodeficiency (CVID) comprises a large heterogeneous group of patients with primary antibody deficiency. Areas covered: The affected patients are characterized by increased susceptibility to infections and low levels of serum immunoglobulin. However, enteropathy, granulomatous organ infiltrates, malignancy, inflammatory and autoimmune conditions are also prevalent. The concomitance of immunodeficiency and autoimmunity appears to be paradoxical and creates difficulties in the management of autoimmune complications affecting these patients. Expert commentary: The management of autoimmunity in patients with CVID requires special considerations because dysregulation and dysfunctions of the immune system along with persistent inflammation impair the process of diagnosis and treatment.
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.
The Journal of Rheumatology · 2024 · 54 citations · open access
Autoinflammatory Diseases: A Review
AbstractAutoinflammatory disease (AID) is a vast spectrum of disorders characterized by recurrent attacks of sterile inflammation. Since the first cloning of the familial Mediterranean fever gene in 1997, there has been a rapid rate of discovery of new AIDs. As of 2022, there have been 485 inborn errors of immunity documented by the International Union of Immunological Societies, for which many display aspects of autoinflammation. The pathophysiology of AIDs is complex. Although many are caused by rare mutations in genes that govern innate immunity, others are polygenic, where disease expression is thought to be triggered by environmental factors in genetically predisposed hosts. AIDs range in prevalence from common entities like gout to ultrarare monogenic diseases. Whereas AIDs were initially studied in pediatric populations, it is now apparent that they can present in adulthood and even in the elderly. AIDs can be clinically challenging given their rarity, as well as the heterogeneity in presentation and underlying etiology. Although the care of AIDs can span medical disciplines, the rheumatologist often plays a central role given the inflammatory nature of these illnesses. In this review, we explore the current understanding of the pathophysiology of these complex conditions and propose a classification system for AIDs. We place an emphasis on AIDs that present to the adult rheumatologist and discuss important AIDs that can mimic more classic rheumatic diseases such as systemic lupus erythematosus and inflammatory arthritis. Finally, we offer an approach to the clinical assessment, diagnosis, and management of AIDs.
Annual Review of Immunology · 2021 · 18 citations · open access
Genetics of Pediatric Immune-Mediated Diseases and Human Immunity
AbstractPrimary immunodeficiency diseases (PIDs) are a rapidly growing, heterogeneous group of genetically determined diseases characterized by defects in the immune system. While individually rare, collectively PIDs affect between 1/1,000 and 1/5,000 people worldwide. The clinical manifestations of PIDs vary from susceptibility to infections to autoimmunity and bone marrow failure. Our understanding of the human immune response has advanced by investigation and discovery of genetic mechanisms of PIDs. Studying patients with isolated genetic variants in proteins that participate in complex signaling pathways has led to an enhanced understanding of host response to infection, and mechanisms of autoimmunity and autoinflammation. Identifying genetic mechanisms of PIDs not only furthers immunological knowledge but also benefits patients by dictating targeted therapies or hematopoietic stem cell transplantation. Here, we highlight several of these areas in the field of primary immunodeficiency, with a focus on the most recent advances.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
