DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for selective IgA deficiency disease — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSelective IgA deficiency disease maps to a 6-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 selective iga deficiency disease 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
interferon induced with helicase C domain 1 (IFIH1) — IFIH1 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9LOV · 3.07 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Selective IgA deficiency is the most common primary immunodeficiency, defined by a decreased serum level of IgA with normal levels of other immunoglobulins. Most individuals are asymptomatic and identified coincidentally, but some present with recurrent respiratory and gastrointestinal infections, allergic disorders, and autoimmune manifestations. The frequency among 4,799 blood donors in Iceland was 1:533, and 1:340 among 1,017 Rh negative women screened, giving a combined frequency of 1:485. A separate 1981 study found that among 37 patients with selective IgA deficiency, those with disease had coexisting IgG2 deficiency, while healthy subjects did not.
The pathogenesis involves a maturation defect in B cells to produce IgA. Alterations in the transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, which likely lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility. A 2024 review notes that the exact pathogenesis remains unknown, and defects in B-cell development, IgA class switch recombination, synthesis, secretion, and long-term survival of IgA switched memory B cells and plasma cells may contribute.
A 2018 study of systemic ozone therapy by rectal insufflation in IgA deficiency patients reported that one month after 12 weeks of treatment, 70% of the experimental group had significant increases in IgG and IgM, while the control group did not. Complete therapeutic response was achieved in 85% of the experimental group and 45% of the control group. Mild, transient adverse events occurred in both groups. No replacement therapy exists for IgA deficiency, and treatment consists of prevention and management of infections and associated conditions.
What is still missing is a clear genetic basis, as the genetic predictors remain early and the exact cellular pathways are not fully understood. No large randomised controlled trials exist for any intervention, and patient stratification by IgG subclass deficiency or genetic subtype has not been prospectively tested.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Immunology · 2010 · 579 citations · open access
Selective IgA Deficiency
AbstractINTRODUCTION: Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. IGA AND ITS FUNCTIONS: Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals. PATHOGENESIS: In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency. CONCLUSION: The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency.
New England Journal of Medicine · 1981 · 325 citations
IgG Subclasses in Selective IgA Deficiency
AbstractA SELECTIVE deficiency in IgA appears in about one in 700 persons.1 Many of these persons are healthy,2 but there is an increased frequency of infections, autoimmune disorders, atopy, and malabsorption syndromes in such subjects.3 In an attempt to explain why some IgA-deficient patients have illnesses and others do not, we measured IgG subclasses in patients with selective IgA deficiency with and without disease. We found coexisting IgG2 deficiency in some of the diseased patients but not in the healthy subjects.MethodsWe obtained serum samples from 37 patients (22 children one to 14 years old and 15 adults) with . . .
FREQUENCY OF IgA DEFICIENCY IN BLOOD DONORS AND Rh NEGATIVE WOMEN IN ICELAND
AbstractSera from 6,842 individuals were tested for IgA deficiency, using double and radial immunodiffusion. Sera containing less than 1 mg/100 ml of IgA were classified as deficient. The frequency of selective IgA deficiency among 4,799 blood donors investigated was 1:533, but 1:340 among 1,017 Rh negative women screened and 1:485 for both groups combined. One of the nine IgA deficient blood donors detected belonged to a 1st cousin marriage family previously investigated, in which the mother also was deficient in IgA. One IgA deficient recipient was found among 704 hospital patients screened for this abnormality.
Systemic Ozone Therapy by Rectal Insufflation for Immunoglobulin A Deficiency
AbstractINTRODUCTION: IgA deficiency is a primary immunodeficiency predominantly due to an antibody defect, for which there is no replacement therapy. Treatment consists of prevention and treatment of infections and other associated conditions. Given the immunomodulatory and regulatory properties of the redox balance of ozone therapy in infectious and inflammatory conditions, evaluation of its effect on IgA deficiency is of interest. OBJECTIVE: Assess the benefits and possible adverse effects of ozone treatment in patients with IgA deficiency. METHODS: of body surface area subcutaneously, once weekly for 12 weeks. Frequency of appearance and severity of clinical symptoms and signs of associated diseases, serum immunoglobulin concentrations and balance of pro-oxidant and antioxidant biomarkers were recorded at treatment initiation and one month after treatment completion. Therapeutic response was defined as complete, partial, stable disease or progressive disease. Descriptive statistics and significance were calculated to compare groups and assess effect size. RESULTS: One month after treatment completion, 70% of patients in the experimental group experienced significant increases in IgG(p = 0.000) and IgM (p = 0.033). The experimental group also displayed decreased pro-oxidation biomarkers, glutathione modulation and increased antioxidant enzymes, with reduced oxidative stress; none of these occurred in the control group. Complete therapeutic response was achieved in 85% of patients in the experimental group and only 45% in the control group. Mild, transient adverse events were reported in both groups. CONCLUSIONS: Ozone therapy by rectal insufflation is a suitable therapeutic option for treating IgA deficiency because it produces antioxidant and immunomodulatory effects and is feasible, safe and minimally invasive. CONTRIBUTION OF THIS RESEARCH: This paper introduces in Cuba a new treatment a for IgA deficiency, with immunomodulatory and antioxidant effects offering substantial clinical benefits to patients with this immunodeficiency.
Expert Review of Molecular Diagnostics · 2024 · 1 citations
An overview of early genetic predictors of IgA deficiency
AbstractINTRODUCTION: Inborn errors of immunity (IEIs) refer to a heterogeneous category of diseases with defects in the number and/or function of components of the immune system. Immunoglobulin A (IgA) deficiency is the most prevalent IEI characterized by low serum level of IgA and normal serum levels of IgG and/or IgM. Most of the individuals with IgA deficiency are asymptomatic and are only identified through routine laboratory tests. Others may experience a wide range of clinical features including mucosal infections, allergies, and malignancies as the most important features. IgA deficiency is a multi-complex disease, and the exact pathogenesis of it is still unknown. AREAS COVERED: This review compiles recent research on genetic and epigenetic factors that may contribute to the development of IgA deficiency. These factors include defects in B-cell development, IgA class switch recombination, synthesis, secretion, and the long-term survival of IgA switched memory B cells and plasma cells. EXPERT OPINION: A better and more comprehensive understanding of the cellular pathways involved in IgA deficiency could lead to personalized surveillance and potentially curative strategies for affected patients, especially those with severe symptoms.
Revista chilena de pediatría · 1992 · 0 citations · open access
Deficiencia selectiva de inmunoglobulina A (IgA)
AbstractA nine year old male with selective IgA deficiency was detected while performing a study on healthy children s rnrrunoglobulm levels from etropolitan Santiago, Chile. Non detectable serum levels of IgA were repeatedly recorded, but no ether clinical or laboratory abnormality, neither family or personal history of significant previous disease we r e detected even thougn they were carefully searched for
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.
