DeCure for Immunodeficiency 72 with autoinflammation
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 72 with autoinflammation — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleImmunodeficiency 72 with autoinflammation maps to a 3-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 72 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.
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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
Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiency syndromes. Patients have low serum immunoglobulins and increased susceptibility to infections, but also frequently develop enteropathy, granulomatous organ infiltrates, malignancy, and inflammatory or autoimmune conditions. The coexistence of immunodeficiency and autoimmunity is described as paradoxical and creates diagnostic and therapeutic difficulties because immune dysregulation and persistent inflammation impair standard management. A 2016 review notes that treating autoimmunity in CVID requires special considerations, but does not report any specific drug trial results, response rates, or survival data.
Primary immunodeficiency disorders in general are often complicated by autoimmune and inflammatory conditions. A 2008 review describes mechanisms linking the two, such as increased homeostatic proliferation in lymphopenic states and defects in regulatory T cells in Wiskott-Aldrich syndrome. Impairment of negative regulatory mechanisms in innate immune cells can also drive inappropriate inflammation. The review suggests that understanding these pathways might lead to more targeted therapies for autoimmune complications, but it provides no concrete efficacy data from clinical studies.
Autoinflammatory diseases (AIDs) are a broad spectrum of disorders marked by recurrent sterile inflammation. As of 2022, the International Union of Immunological Societies had documented 485 inborn errors of immunity, many with autoinflammatory features. AIDs range from common entities like gout to ultrarare monogenic diseases, and can present in childhood, adulthood, or old age. A 2024 review emphasises the heterogeneity in presentation and underlying etiology, and notes that clinical assessment and diagnosis remain challenging. It does not report any treatment outcomes, response rates, or survival figures for any specific drug.
No abstract provides evidence for any drug treatment in immunodeficiency 72 with autoinflammation specifically. The literature reviewed describes the general complexity of managing autoimmunity in primary immunodeficiency and the broad landscape of autoinflammatory diseases, but no trial data, sample sizes, or survival statistics are given for any intervention. What is missing are dedicated clinical trials, patient stratification by genetic subtype, and funding to study this particular condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
American Journal of Rhinology and Allergy · 2013 · 77 citations
Common Variable Immunodeficiency
AbstractCommon variable immunodeficiency (CVID) is a common primary immunodeficiency characterized by a failure in B-cell differentiation with defective immunoglobulin production. Affected patients are uniquely susceptible to recurrent infection with encapsulated organisms and have an increased propensity for the development of inflammatory and autoimmune manifestations. The diagnosis of CVID is commonly delayed and the underlying cause of the disorder is not understood. Replacement antibody therapy reduces the risk of serious infections. However, optimal treatment regimens for the uncommon manifestations associated with this disease, such as granulomatous lymphocytic interstitial lung disease, require further research.
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.
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.
