DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency, common variable, 7 — 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, common variable, 7 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, common variable, 7 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
complement C3d receptor 2 (CR2) — CR2 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 ndgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1GHQ · 2.04 Å · ligand 2-acetamido-2-deoxy-alpha-D-glucopyranose (NDG). Experimental structure, not a prediction.
What the evidence adds up to
Common variable immunodeficiency disorders are a mixed group of heterogeneous conditions linked by lack of immunoglobulin production and primary antibody failure, and this variability makes coherent sense of immunopathogenesis or the role of genetic abnormalities difficult. The diagnosis can be challenging because symptoms are non-specific and heterogeneous, and due to this heterogeneous presentation including a heightened rate of infections, diagnosis is often delayed for 4 to 9 years, a delay that may contribute to increased morbidity and mortality. Radiological findings and clinical suspicion could be helpful in diagnosing the condition, thereby decreasing associated mortality and morbidity.
Cellular phenotypes and abnormalities have been described in both adaptive and innate immune responses, and several classifications are based on defects found on T and B cells that have been correlated with clinical manifestations. Significant progress has been made in elucidating genetic mechanisms, and massive sequencing technologies have favoured the description of mutations in several genes, but only in 2% to 10% of patients. These monogenetic defects include ICOS, TNFRSF13B (TACI), TNFRS13C (BAFFR), TNRFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), CD27, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R, VAV1, RAC1, BLK, IKZF1 (IKAROS) and IRF2BP2.
In one genetic evaluation study of 185 patients suspected of immunodeficiency without a definitive diagnosis, 58.56% were male, the average age was 9.28±5.40 years, and consanguineous marriage of parents was observed in 79.8% of cases. Pneumonia with 33.51% was the most common clinical manifestation. In total, 41.14% of patients suffered from combined immunodeficiency, 26.86% had defects of phagocyte number or function or both, and 24% had predominantly antibody deficiencies. CVID was detected in 12% of patients. In 37.04% of the identified genes, there was a discrepancy between clinical and genetic diagnosis.
The recent attempt to collate the varied complications and define particular clinical phenotypes has improved understanding, but these definitions need to be refined and confirmed by other studies to improve accuracy of prognosis and management. What is still missing is a coherent framework that reconciles the genetic heterogeneity with the clinical variability, larger studies that can confirm proposed phenotype definitions, and a trial design that can stratify patients by the specific monogenetic defects found in only a small minority.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Haematology · 2009 · 392 citations · open access
Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions
AbstractThe common variable immunodeficiency disorders are a mixed group of heterogeneous conditions linked by lack of immunoglobulin production and primary antibody failure. This variability results in difficulty in making coherent sense of either immunopathogenesis or the role of various genetic abnormalities reported in the literature. The recent attempt to collate the varied complications in these conditions and to define particular clinical phenotypes has improved our understanding of these diseases. Once refined and confirmed by other studies, these definitions will facilitate improved accuracy of prognosis and better management of clinical complication. They may also provide a method of analysing outcomes as related to new immunopathological and genetic findings.
Revista Alergia México · 2017 · 8 citations · open access
Alteraciones inmunológicas en la inmunodeficiencia común variable
AbstractCommon variable immunodeficiency (CVID) is the largest group of symptomatic primary immune deficiencies; it is characterized by hypogammaglobulinemia, poor response to vaccines and increased susceptibility to infections. Cellular phenotypes and abnormalities have been described both in adaptive and innate immune response. Several classifications of common variable immunodeficiency are based on defects found on T and B cells, which have been correlated with clinical manifestations. In recent years, significant progress has been made in elucidating the genetic mechanisms that result in a IDCV phenotype. Massive sequencing technologies have favored the description of mutations in several genes, but only in 2 % to 10 % of patients. These monogenetic defects are: ICOS, TNFRSF13B (TACI), TNFRS13C (BAFFR), TNRFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), (CD27), LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R, VAV1, RAC1, BLK, IKZF1 (IKAROS) and IRF2BP2. These findings have provided a possible explanation for the pathogenesis of IDCV, since these molecules play an important role in the co-operation between B and T cells in the germinal center, as well as in intrinsic signaling pathways of both.
Common variable immunodeficiency diagnosed by capsule endoscopy
AbstractCommon variable immunodeficiency (CVID) is the most frequent primary immunodeficiency, characterized by reduced levels of immunoglobulins [1] [2]. Due to a heterogeneous presentation including a heightened rate of infections, the diagnosis is often delayed for 4 – 9 years. This delay may contribute to the increased morbidity and mortality in CVID patients [1] [3].
Indian Journal of Allergy Asthma and Immunology · 2021 · 0 citations · open access
Imaging findings in common variable immunodeficiency
AbstractCommon variable immunodeficiency is characterized by decreased levels of immunoglobulins leading to repeated infections of chest, gastrointestinal tract, etc., Radiological findings and clinical suspicion could be helpful in diagnosing common variable immunodeficiency thereby decreasing mortality and morbidity associated with disease. We present radiological findings in a 20-year-old patient with laboratory findings supporting the diagnosis of common variable immunodeficiency.
Malaysian Journal of Paediatrics and Child Health · 2023 · 0 citations · open access
Common Variable Immunodeficiency: A Paradox of Immunodeficiency and Autoimmunity
AbstractCommon variable immunodeficiency disorders (CVID) are the most common form of symptomatic primary immunodeficiency. The diagnosis of CVID can be challenging as the symptoms are non-specific and heterogenous in nature. In light of this, a broad review of this disease is presented here based on the important clinical symptoms, complications and management.
Immunology and Genetics Journal · 2024 · 0 citations
Genetic Evaluation of Patients Suspected of Immunodeficiency Referred to the Immunodeficiency Clinic of Akbar Hospital in Mashhad
AbstractBackground: The purpose of this study was genetic evaluation of patients suspected of immunodeficiency, without a definitive diagnosis, referred to the Immunodeficiency Clinic of Akbar Hospital in Mashhad in 2021-2022. Methods: In this study, patients suspected of immunodeficiency, without a definitive diagnosis, referred to an immunodeficiency clinic were included A complete clinical and paraclinical examination has been done by expert specialists and clinical geneticists. Blood samples were taken for genetic analysis using the Exome Sequencing technique followed by comprehensive bioinformatics analysis. Parents and healthy offspring were assessed for the candidate gene variants. Results: In this study, 185 patients were included; 58.56% of them were male; The average age of the participants was 9.28±5.40 years, and consanguineous marriage of parents was observed in 79.8 % of cases. Pneumonia with 33.51% was the most common clinical manifestation in patients with suspected immunodeficiency. In total, 41.14% of patients suffered from combined immunodeficiency, 26 .86% of them had defects of phagocyte number, function, or both; and 24% had predominantly antibody deficiencies. Hyper IgE syndrome was detected in 16% of patients, SCID and CGD each in 14.86% of patients, CVID in 12% of patients, and LAD in 7.43% of them. In 37.04% of the identified genes, there was a discrepancy between clinical and genetic diagnosis in patients. Conclusion: The most common clinical manifestation of patients suspected of primary immunodeficiency is pneumonia; therefore, patients who suffer from recurrent respiratory infections should be checked for genetic immunodeficiency. In this study, most patients were in the groups of immunodeficiencies affecting multiple cell types, defects of phagocyte number, function, or both; and predominantly antibody deficiencies, respectively. The most common diseases diagnosed were: Hyper IgE syndrome, SCID and CGD, CVID, and LAD.
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.
