DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 87 and autoimmunity — 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 87 and autoimmunity 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 87 and autoimmunity 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.
What the evidence adds up to
Intravenous immunoglobulin is used as replacement therapy in primary immunodeficiency diseases and as an immunomodulatory agent in autoimmune and inflammatory disorders, though its mechanisms of action are complex and not well understood for some conditions. A 2015 classification update from the International Union of Immunological Societies reported 34 new gene defects in primary immunodeficiencies, noting an increasing overlap between immunodeficiency—manifested by infection or malignancy—and immune dysregulation, including autoimmunity and allergy. The same review states that ideal diagnosis and suitable treatment remain key to successful management, but many patients are diagnosed late, suffering from chronic infections, end-organ damage, or death before diagnosis.
A 2018 case report describes a 24-year-old woman with relapsing and remitting multiple sclerosis who was treated with daclizumab, a monoclonal antibody blocking CD25. After six months of therapy, she presented with febrile neutropenia; bone marrow biopsy showed agranulocytosis with a maturation block at the myeloblast stage. Neutrophil recovery occurred only after daclizumab was stopped and T cell immunosuppressive agents—systemic corticosteroids and methotrexate—were started. The patient was found to have a novel heterozygous missense variant in CTLA4, leading to a diagnosis of CTLA-4 haploinsufficiency with autoimmune infiltration (CHAI). The authors note that autoimmune disease may be the presenting feature of primary immunodeficiency and should be investigated before starting immunotherapy, as genetic clarification can alter the safety of the proposed treatment.
A 1999 review discusses approved, new, and controversial indications for intravenous immunoglobulin, including its use in primary immunodeficiency and autoimmune disorders, but does not provide specific survival or response rate data. A 2013 introduction to severe combined immunodeficiency and combined immunodeficiency outlines therapeutic options from prophylactic anti-infective measures to hematopoietic stem cell transplantation and gene therapy, without reporting trial results. A 2021 review states that systemic immunodeficiency disorders are heterogeneous and that the percentage of these disorders is increasing among the population, but provides no quantitative evidence for this claim.
What is still missing are large, controlled trials that stratify patients by specific genetic defects—such as CTLA4 haploinsufficiency—before testing immunomodulatory therapies. The 2018 case report highlights that even a well-established drug like daclizumab can cause life-threatening agranulocytosis in an unrecognised primary immunodeficiency patient, yet no prospective study has addressed this risk. Funding for genetic screening before immunotherapy, and for trials that separate immunodeficiency from autoimmunity phenotypes, remains 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.
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.
An Update on the Use of Immunoglobulin for the Treatment of Immunodeficiency Disorders
AbstractFor patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement.
Current Opinion in Pediatrics · 1999 · 23 citations
Supply, use, and abuse of intravenous immunoglobulin
AbstractIntravenous immunoglobulin is used as a replacement therapy in primary immunodeficiency diseases as well as an immunomodulatory agent in a variety of autoimmune and inflammatory disorders. The mechanisms of intravenous immunoglobulin action are complex and, for some disorders, not well understood. This paper reviews the recent literature and discusses approved, new, and controversial indications for intravenous immunoglobulin therapy, with special emphasis on its mechanism of action.
Allergy Asthma and Clinical Immunology · 2018 · 13 citations · open access
Pitfalls of immunotherapy: lessons from a patient with CTLA-4 haploinsufficiency
AbstractDaclizumab is a humanized monoclonal antibody that blocks CD25, the high affinity alpha subunit of the interleukin-2 receptor. Daclizumab therapy targets T regulatory cell and activated effector T cell proliferation to suppress autoimmune disease activity, in inflammatory conditions like relapsing and remitting multiple sclerosis. Here, we present the first report of agranulocytosis with daclizumab therapy in a patient with relapsing and remitting multiple sclerosis. Our patient was a 24-year-old Australian female with a clinical history of atopy, lymphocytic enteritis complicated by B12 deficiency, relapsing and remitting multiple sclerosis, recurrent lower respiratory tract infections, vulval/cervical intraepithelial neoplasia and melanoma. She was commenced on daclizumab therapy after failing several lines of treatment for relapsing and remitting multiple sclerosis. During a hospital admission for lymphocytic enteritis, she was incidentally diagnosed with combined immunodeficiency with hypogammaglobulinaemia and declined proposed regular intravenous immunoglobulin infusions. Following six months of daclizumab therapy, our patient presented to hospital with febrile neutropenia. No clear infective cause was found, despite numerous investigations. However, bone marrow biopsy revealed agranulocytosis with an apparent maturation block at the myeloblasts stage. Neustrophil recovery occurred following cessation of daclizumab and the initiation of T cell immunosuppressive agents including systemic corticosteroids and methotrexate. The patient was further investigated for combined immunodeficiency and whole exome sequencing revealed a novel heterozygous missense variant in cytotoxic T lymphocyte antigen 4 ( CTLA4 ), leading to a diagnosis of CTLA-4 haploinsufficiency with autoimmune infiltration (CHAI). This case demonstrates that autoimmune disease may be the presenting feature of primary immunodeficiency and should be appropriately investigated prior to the commencement of immunotherapy. Genetic clarification of underlying primary immunodeficiency may provide critical clinical information that alters the safety of the proposed treatment strategy.
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.
Oxford University Press eBooks · 2013 · 0 citations
Introduction to Severe Combined Immunodeficiency (SCID) and Combined Immunodeficiency (CID)
AbstractPrimary immunodeficiency diseases are inherited disorders that affect human adaptive and innate immunity. In most cases, affected individuals experience recurrent infections, but they may also suffer from autoimmune diseases and malignancies. This chapter focuses on Introduction to Severe Combined Immunodeficiency (SCID) and Combined Immunodeficiency (CID) including the historic and scientific background, clinical presentations, immunologic characteristics, and the molecular/genetic underpinnings. Where appropriate, diagnostic tools and therapeutic options are outlined -- from prophylactic anti-infective measures to hematopoietic stem cell transplantation and gene therapy.
Greater South Information System · 2015 · 0 citations · open access
Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015
AbstractWe report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In the two years since the previous version, 34 new gene defects are reported in this updated version. For each disorder, the key clinical and laboratory features are provided. In this new version we continue to see the increasing overlap between immunodeficiency, as manifested by infection and/or malignancy, and immune dysregulation, as manifested by auto-inflammation, auto-immunity, and/or allergy. There is also an increased number of genetic defects that lead to susceptibility to specific organisms which reflects the finely tuned nature of immune defense systems. This classification is the most up to date catalogue of all known and published primary immunodeficiencies and acts as a current reference of the knowledge of these conditions and is an important aid for the genetic and molecular diagnosis of patients with these rare diseases.
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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