DeCure for Immunodeficiency 115 with autoinflammation
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 115 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 115 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 115 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
ring finger protein 31 (RNF31) — RNF31 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 2-oxidanylidene-5,6,7,8-tetrahydro-1~{h}-quinolin-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6SC5 · 2.1 Å · ligand methyl 4-[(2-oxidanylidene-5,6,7,8-tetrahydro-1~{H}-quinolin-3-yl)carbonylamino]but-3-enoate (L6B). Experimental structure, not a prediction.
What the evidence adds up to
Primary immunodeficiency diseases, including common variable immunodeficiency, are characterised by increased susceptibility to infection but also by troublesome and sometimes life-threatening autoimmune complications. The concomitance of immunodeficiency and autoimmunity appears paradoxical and creates difficulties in management. A 2002 review noted that understanding the molecular basis of these disorders had led to more focused treatment, but the review itself provided no new trial data. A 2008 review described mechanisms linking immunodeficiency to autoimmunity, such as increased homeostatic proliferation in lymphopenia and defects in regulatory T cells in Wiskott-Aldrich syndrome, but again offered no patient outcomes. A 2016 review of common variable immunodeficiency stated that enteropathy, granulomatous organ infiltrates, malignancy, and inflammatory conditions are prevalent, and that dysregulation of the immune system along with persistent inflammation impairs diagnosis and treatment. No specific drug, response rate, or survival figure appears in any of these abstracts.
A 2021 review noted that primary immunodeficiencies affect between 1 in 1,000 and 1 in 5,000 people worldwide, and that identifying genetic mechanisms can dictate targeted therapies or haematopoietic stem cell transplantation. However, the abstract gives no numbers for how many patients receive such therapies or with what success. The same review states that studying patients with isolated genetic variants has enhanced understanding of host response to infection and mechanisms of autoimmunity and autoinflammation, but it does not report any clinical trial results.
Across all four abstracts, no concrete survival data, response rates, or sample sizes are provided. No drug is named, and no treatment is shown to be effective in a controlled study. The reviews repeatedly call for better understanding and more targeted therapies, but they do not supply evidence that any existing intervention changes outcomes for patients with immunodeficiency and autoinflammation. What is still missing are prospective trials that stratify patients by genetic defect, funding for such trials, and a standardised approach to measuring autoimmune complications in these rare, heterogeneous populations.
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.
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.
Experimental Biology and Medicine · 2021 · 30 citations · open access
Minireview: Insights into anti-interferon-γ autoantibodies
AbstractThe association between the presence of anti-interferon-γ autoantibodies and the onset of immunodeficiency with intracellular infections has been clearly established. No standard regimen to control the production of these pathogenic autoantibodies, apart from antimicrobial therapy to eliminate infections, contributes to the medical burden of this syndrome, which sometimes has a fatal outcome. In this review, we summarize the findings on anti-interferon-γ autoantibodies to facilitate further research and to provide guidance for treatment strategies.
British Society for Immunology and United Kingdom Primary Immunodeficiency Network (UKPIN) consensus guideline for the management of immunoglobulin replacement therapy
AbstractCurrently, there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence, a modified Delphi approach was used covering statements for the initiation, monitoring, discontinuation of IgRT as well as home therapy programme. A group of six consultant immunologists and three nurse specialists created the statements, reviewed responses and feedback and agreed on final recommendations. This guideline includes 22 statements for initiation, 22 statements for monitoring, 11 statement for home therapy, and 19 statements for discontinuation of IgRT. Further areas of research are proposed to improve future delivery of care.
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.
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.
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.
