DeCure for Combined immunodeficiency due to LRBA deficiency
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for combined immunodeficiency due to LRBA deficiency — 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 moduleCombined immunodeficiency due to LRBA deficiency 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 combined immunodeficiency due to lrba deficiency 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
LPS responsive beige-like anchor protein (LRBA) — LRBA 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1T77 · 2.4 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
LRBA deficiency is a primary immunodeficiency disorder that can cause a common variable immunodeficiency (CVID)-like disease. Typical features include autoimmunity, chronic diarrhoea, and hypogammaglobulinaemia. In a 2020 case report, a 7-year-old female with LRBA deficiency presented with acute cervical longitudinally extensive transverse myelitis (LETM), described as the first such case in the literature. Neurological complications are reported in patients with LRBA deficiency.
A 2019 Colombian study evaluated LRBA protein expression in 112 patients with a clinical phenotype associated with LRBA deficiency. LRBA expression varied greatly between healthy donors and patients. Six patients showed decreased LRBA protein expression, but no pathogenic or likely pathogenic biallelic variants were found in LRBA or in other immune-related genes. The authors concluded that other genetic, epigenetic, or environmental mechanisms might regulate LRBA expression. No patients with LRBA deficiency had been reported in Colombia prior to this study.
The broader context of common variable immunodeficiency includes that it is the most frequent clinically manifested primary immunodeficiency, marked by quantitative and functional deficiencies in B and T lymphocytes, most commonly associated with deficient antibody production. Around 38% of individuals with CVID develop autoimmune diseases due to disrupted immune regulation. A 2025 review found an inverse correlation between reduced number and functional activity of T-regulatory lymphocytes in CVID patients and the activation of clinical symptoms of secondary systemic vasculitis, attributed to depletion of immune response reserve capabilities.
What remains missing is a clear genetic diagnosis for patients with reduced LRBA expression but no identifiable biallelic mutations, limiting the ability to stratify patients or design targeted trials. The neurological complications of LRBA deficiency are only beginning to be documented, with no systematic data on frequency or progression. Funding for larger, multi-centre natural history studies and for functional work on epigenetic or environmental regulation of LRBA expression is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Internal Medicine · 1980 · 61 citations · open access
Mild Hypertension: Natural History and Management.
Abstractto concentrate on the recent advances in this field.The second part of the book is devoted to various papers on purine metabolic defects in immunode- ficiency.There is a good deal of clinical and biochemical detail here for those interested in purine nucleoside phosphorylase and adenosine deaminase deficiency.The third part consists of a series of papers on phagocytic defects which includes reviews, single case reports, hypotheses and technical innovations.This book is of interest to the connoisseur of lymphocyte and neutrophil defects, but it is too specialized and fragmented for those seeking a more general approach to the management and diagnosis of immunodeficiency.
International Journal of Immunogenetics · 2007 · 31 citations · open access
Genetic defects in common variable immunodeficiency
AbstractCommon variable immunodeficiency (CVID) is the most frequent clinically manifested primary immunodeficiency. According to clinical and laboratory findings, CVID is a heterogeneous group of diseases. Recently, the defects of molecules regulating activation and terminal differentiation of B lymphocytes have been described in some patients with CVID. In this study, we show the overview of deficiencies of inducible costimulator, transmembrane activator and calcium-modulator and cytophilin ligand interactor, CD19 molecules, their genetic basis, pathogenesis and clinical manifestations.
Frontiers in Pediatrics · 2020 · 5 citations · open access
Acute Cervical Longitudinally Extensive Transverse Myelitis in a Child With Lipopolysaccharide-Responsive-Beige-Like-Anchor-Protein (LRBA) Deficiency: A New Complication of a Rare Disease
AbstractLipopolysaccharide responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disorder (PID) that can cause a common variable immunodeficiency (CVID)-like disease. The typical features of the disease are autoimmunity, chronic diarrhea, and hypogammaglobulinemia. Neurological complications are also reported in patients affected by LRBA deficiency. We describe a 7-year old female with an acute cervical longitudinally extensive transverse myelitis (LETM) as a feature of LRBA deficiency. This is the first case of LETM associated with LRBA deficiency described in literature.
Colombia medica · 2019 · 5 citations · open access
Clinical, immunological and genetic characteristic of patients with clinical phenotype associated to LRBA-deficiency in Colombia.
AbstractBackground: LPS-responsive beige -like anchor protein (LRBA) deficiency is a primary immunodeficiency disease caused by loss of LRBA protein expression, due to biallelic mutations in LRBA gene. LRBA deficiency patients exhibit a clinically heterogeneous syndrome. The main clinical complication of LRBA deficiency is immune dysregulation. Furthermore, hypogammaglobulinemia is found in more than half of patients with LRBA-deficiency. To date, no patients with this condition have been reported in Colombia Objective: To evaluate the expression of the LRBA protein in patients from Colombia with clinical phenotype associated to LRBA-deficiency. Methods: In the present study the LRBA-expression in patients from Colombia with clinical phenotype associated to LRBA-deficiency was evaluated. After then, the clinical, the immunological characteristics and the possible genetic variants in LRBA or other genes associated with the immune system in patients that exhibit decrease protein expression was evaluated. Results: In total, 112 patients with different clinical manifestations associated to the clinical LRBA phenotype were evaluated. The LRBA expression varies greatly between different healthy donors and patients. Despite the great variability in the LRBA expression, six patients with a decrease in LRBA protein expression were observed. However, no pathogenic or possible pathogenic biallelic variants in LRBA, or in genes related with the immune system were found. Conclusion: LRBA expression varies greatly between different healthy donors and patients. Reduction LRBA-expression in 6 patients without homozygous mutations in LRBA or in associated genes with the immune system was observed. These results suggest the other genetic, epigenetic or environmental mechanisms, that might be regulated the LRBA-expression.
Proceedings of the Shevchenko Scientific Society Medical Sciences · 2025 · 2 citations · open access
T-REGULATORY LYMPHOCYTES IN PATIENTS WITH ANTIBODY DEFICIENCY AND MANIFESTATIONS OF SECONDARY SYSTEMIC VASCULITIS
AbstractThe review focused on analyzing clinical and immunological peculiarities in patients with common variable immunodeficiency, with and without manifestations of secondary systemic vasculitis. CVID is a primary immunodeficiency marked by quantitative and functional deficiencies in B and T lymphocytes. However, it is most commonly associated with a deficiency in antibody production. Around 38% of individuals with common variable immunodeficiency develop autoimmune diseases as a result of disrupted immune regulation. The outcomes of the clinical progression analysis and laboratory immunological changes in patient groups being compared are presented. The results suggest an inverse correlation between the reduction in the number and functional activity of T-regulatory lymphocytes in patients with common variable immunodeficiency and the activation of clinical symptoms of secondary systemic vasculitis in these patients, primarily due to the depletion of the immune response’s reserve capabilities. A deeper understanding of the risks associated with the dysregulation of immune surveillance in patients with common variable immunodeficiency and secondary systemic vasculitis will enable the prescription of modern comprehensive replacement and immunopathogenetic therapy.
Oligoclonal T Cells and B Cells in an Amish Girl With Atypical RAG-1 Deficient Severe Combined Immunodeficiency
AbstractWe report a 5-month-old Amish girl with atypical recombinase-activating gene (RAG)-deficient severe combined immunodeficiency disease. There was a lys992glu RAG-1 substitution leading to impaired RAG activity. Immunological studies revealed mildly decreased CD3+ T cells, markedly decreased CD4+ T cells, and oligoclonal T-cell receptor-Vβ T cells. B cells were markedly decreased but serum immunoglobulin levels were normal with monoclonal IgG and IgM antibodies.
Oxford University Press eBooks · 2013 · 0 citations
Primary immunodeficiency
AbstractIntroduction Classification of immunodeficiency Clinical features of immunodeficiency Investigation of immunodeficiency Laboratory investigation Major B-lymphocyte disorders Rare antibody deficiency syndromes X-linked agammaglobulinaemia (Bruton’s disease) Common variable immunodeficiency (CVID) CVID 2: complications and treatment Selective IgA deficiency IgG subclass deficiency Specific antibody deficiency with normal serum immunoglobulins...
British Journal of Clinical Pharmacology · 1985 · 0 citations · open access
Lack of inhibition of purine nucleoside phosphorylase and adenosine deaminase in patients treated with azathioprine.
AbstractDeficiency of the purine salvage enzymes purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) are known causes of immunodeficiency. Evidence for inhibition of these enzymes was sought in 16 patients on azathioprine therapy by testing for deoxyguanosine (PNP deficiency) and deoxyadenosine (ADA deficiency) in urine using a novel phosphorescence method. These abnormal nucleosides were not found in urine of azathioprine treated patients or in 30 normal controls but were easily detected in urine from proven cases of PNP and ADA deficiency suggesting lack of in vivo inhibition of PNP and ADA by azathioprine.
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.
