DeCure for Immunodeficiency 98 with autoinflammation, X-linked
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency 98 with autoinflammation, X-linked — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleImmunodeficiency 98 with autoinflammation, X-linked maps to a 2-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 98 with autoinflammation, x-linked 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
toll like receptor 8 (TLR8) — TLR8 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 d87drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3WN4 · 1.81 Å · ligand 2-butylfuro[2,3-c]quinolin-4-amine (D87). Experimental structure, not a prediction.
What the evidence adds up to
A 2000 case report describes correction of hyper-IgM syndrome after liver and bone marrow transplantation. The syndrome is characterised by neutropenia, defective B-cell isotype switching, elevated or normal serum IgM, and low serum IgG, IgA, and IgE. Patients suffer serious pyogenic infections from encapsulated bacteria and are susceptible to intracellular pathogens such as Pneumocystis carinii, Cryptosporidium parvum, and leishmania. Inheritance is usually X-linked, though autosomal recessive and dominant forms exist. The report does not provide survival or response rates, nor does it specify the number of patients treated.
A 2002 review states that molecular biological techniques have allowed new, therapeutically useful treatments for X-linked severe combined immunodeficiency to be introduced into clinical practice. It does not name any specific drug or provide quantitative outcomes. A 2023 review of HIV-associated rheumatic diseases notes that highly active antiretroviral therapy and subsequent immune restoration have been linked to the resurgence of multiple immune-mediated diseases in the HIV population. This abstract does not address primary immunodeficiency.
A 2020 review of primary immunodeficiency disorders in Egyptian children describes them as inherent immune defects presenting with increased susceptibility to infections, autoimmunity, autoinflammation, allergy, or malignancy. Autosomal recessive disorders are more common due to high consanguinity. The review discusses challenges of establishing a PID service in a resource-limited setting but provides no drug efficacy data. A 2018 review of X-linked immunodeficiency with hyper-immunoglobulin M states the disease is caused by mutation of the CD40 ligand gene, leading to dysfunction of immunoglobulin class switching, with clinical manifestations of recurrent infection, neutropenia, autoimmune disease, or tumour. No treatment outcomes are reported.
What is still missing is any controlled trial of a drug for this specific condition, any data on patient stratification by CD40L mutation type, and funding for prospective studies that measure survival or infection rates after any intervention beyond transplantation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2000 · 104 citations · open access
Correction of the Hyper-IgM Syndrome after Liver and Bone Marrow Transplantation
AbstractThe hyper-IgM syndrome, a rare form of combined primary immunodeficiency, is characterized by neutropenia and defective B-cell isotype switching, which results in elevated or normal levels of serum IgM and low levels of serum IgG, IgA, and IgE.1 Clinically, patients with the syndrome have serious pyogenic infections caused by encapsulated bacteria, suggestive of the presence of humoral immunodeficiency. They are also susceptible to infections with intracellular pathogens such as Pneumocystis carinii, Cryptosporidium parvum, and leishmania, because of a possible defect in cellular immunity.2,3 The inheritance is usually X-linked, but autosomal recessive and autosomal dominant forms have also been documented. . . .
AbstractSevere combined immunodeficiency is one of the most common causes of primary immunodeficiencies in humans. Molecular biological techniques have allowed new, therapeutically useful treatments for these diseases to be introduced into clinical practice. This review will focus on the molecular basis and new treatments for X-linked severe combined immunodeficiency.
AbstractThe most common of the primary immunodeficiency diseases are those that involve inadequate antibody production. The characteristic presentation of these disorders is recurrent sinopulmonary infections. An arrest in B cell development at the pre-B cell stage leads to agammaglobulinemia and an insignificant number of B cells. X-linked agammaglobulinemia is the most common of these developmental arrests while the autosomal recessive agammaglobulinemias comprise a small minority of the total cases. Likewise, the most common form of the hyper-IgM syndromes (CD40 ligand deficiency) is X-linked. Of the autosomal recessive forms, CD40 deficiency is basically identical to the X-linked form in its clinical phenotype where, in addition to inadequate antibody production, there is defective T cell signaling through the CD40-CD40L interaction. Aside from CD40 deficiency, the other recessive forms of hyper-IgM syndrome have adequate T cell function. IgA deficiency is the most common and the most benign of the B cell disorders. Common variable immunodeficiency is diverse in its presentation and clinical course. The pathophysiology of this disease is multifactorial and frequently ill defined, often making it a diagnosis of exclusion. A working knowledge of identifiable PIDDs is essential in both recognizing when to suspect immunodeficiency and making a diagnosis.
JCR Journal of Clinical Rheumatology · 2023 · 3 citations
HIV-Associated Rheumatic Diseases
AbstractABSTRACT: Human immunodeficiency virus (HIV) is widely prevalent among the world population. Although, historically, it has been linked to opportunistic infections in keeping with immunodeficiency and immune dysregulation, it has also been associated with a wide variety of autoimmune manifestations. With the introduction of highly active antiretroviral therapy and subsequent restoration of immunity, there have been multiple immune-mediated diseases that have resurfaced in the HIV population. Our review highlights autoimmune diseases in association with HIV and its targeted therapies in detail.
Clinical Spectrum and Challenges of Primary Immunodeficiency disorders in Egyptian children
AbstractPrimary Immunodeficiency Disorders (PID) are inherent defects of the immune system that may present in infants and children. The main presentations include increased susceptibility to infections (a narrow or broad spectrum of pathogens), autoimmunity, autoinflammation, allergy and/or malignancy. PIDs are increasingly diagnosed and may present with different phenotypes that range from subtle to severe ones. They are classified into ten major categories according to the International Union of Immunological Societies (IUIS). Autosomal recessive disorders are noticeably more common because of the high consanguinity rates in the society. The spectrum of PID is highlighted with a brief walk through the challenges of establishing a PID service in a resource limited setting like catching up with the rapidly changing field, provision of state of the art diagnostic services and actual provision of medical care to PID patients. Several opportunities for growth of the field and overcoming obstacles are discussed.
X-linked immunodeficiency with hyper-immunoglobulin M
AbstractX-linked immunodeficiency with hyper-immunoglobulin(Ig) M is a primary immunodeficiency disease, mainly due to the mutation of coding CD40 ligand(CD40L), which results in the dysfunction of immunoglobulin class switching that causes in a normal or increased IgM level, and a marked decrease in IgG, IgA and IgE level.The clinical manifestations are recurrent infection, neutropenia, and autoimmune disease or tumor.
Key words:
X-linked immunodeficiency with hyper-immunoglobulin M; CD40L gene; Mutation
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.
