DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for common variable immunodeficiency — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCommon variable immunodeficiency maps to a 42-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 common variable immunodeficiency 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
Bruton tyrosine kinase (BTK) — BTK 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 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). 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, which makes coherent sense of immunopathogenesis or genetic abnormalities difficult. In a 2021–2022 study of 185 patients suspected of immunodeficiency without a definitive diagnosis, 12% were found to have CVID. The average age of participants was 9.28 years, and consanguineous marriage was observed in 79.8% of cases. Pneumonia was the most common clinical manifestation, occurring in 33.51% of patients. In 37.04% of identified genes, there was a discrepancy between clinical and genetic diagnosis.
Up to 50% of patients with recalcitrant chronic rhinosinusitis have been found to have immune dysfunction, with CVID and X-linked agammaglobulinemia being the most frequent primary immunodeficiencies studied. Medical therapy, particularly immunoglobulin replacement, appears most effective when administered at high doses early in the disease course. The addition of endoscopic sinus surgery is less clearly supported but may also provide benefit if performed early. Most studies supporting these findings are Level 4 evidence.
CVID is characterised by hypogammaglobulinaemia, poor response to vaccines, and increased susceptibility to infections. Cellular abnormalities have been described in both adaptive and innate immune responses. Genetic defects have been identified in only 2% to 10% of patients, involving genes such as ICOS, TNFRSF13B, CD19, LRBA, CTLA4, NFKB1, and others. These monogenetic defects provide a possible explanation for pathogenesis, as the molecules play roles in B and T cell cooperation and intrinsic signalling pathways.
What is still missing is a coherent framework linking the varied clinical phenotypes to specific immunopathological and genetic findings, which would improve accuracy of prognosis and management of complications. The genetic basis remains unexplained in the vast majority of CVID patients, and the evidence for treatment strategies, particularly surgery, is weak. Funding for large, well-designed prospective studies with clear patient stratification is needed.
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.
International Forum of Allergy & Rhinology · 2016 · 40 citations
Primary immunodeficiency and recalcitrant chronic sinusitis: a systematic review
AbstractBACKGROUND: A subset of patients with chronic rhinosinusitis (CRS) has disease refractory to standard therapies. Primary immunodeficiency should be considered in this group. Past literature has demonstrated an association between immunodeficiency and chronic sinusitis. METHODS: A systematic literature search was performed using OVID, MEDLINE, EMBASE, and Cochrane databases to identify English language papers containing original human data on subjects with primary immunodeficiency and chronic sinusitis. A total of 39 studies met inclusion criteria. Data was collected pertaining to immune dysfunction in patients with chronic sinusitis, the clinical workup for these patients, and the effectiveness of medical and surgical treatments. The studies were assessed to determine their level of evidence. RESULTS: The majority of studies were supported by Level 4 evidence. Up to 50% of patients with recalcitrant CRS were found to have immune dysfunction. The most frequent primary immunodeficiencies studied were common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Common collected data included measurement of serum immunoglobulins and functional antibody responses. Treatments reviewed include immunoglobulin replacement, long-term antibiotics and endoscopic sinus surgery. CONCLUSION: Patients with recalcitrant CRS should be evaluated for primary immunodeficiency. This should include as assessment of quantitative serum immunoglobulin levels as well as functional antibody responses. Medical therapy, particularly immunoglobulin replacement therapy, appears to be most effective when administered at high doses early in the disease course. The addition of surgery is less clearly supported, but may also provide benefit if performed early.
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.
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.
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.
