DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for MHC class I deficiency — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMHC class I deficiency maps to a 4-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 mhc class i 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
transporter 1, ATP binding cassette subfamily B member (TAP1) — TAP1 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9O9D · 2.44 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 93 myositis patients with the CD8-MHC-1 complex pathology, 17 met criteria for polymyositis, 70 for inclusion body myositis, and 6 were unclassifiable. Among treated patients, 11 of 16 with polymyositis and 4 of 6 p62-immunonegative unclassifiable patients responded to immunotherapy, while all 44 treated inclusion body myositis patients and 2 p62-immunopositive unclassifiable patients did not respond. MHC class I immunostaining can differentiate idiopathic inflammatory myopathies from dystrophies: in a study of 40 muscle biopsies, polymyositis and sporadic inclusion body myositis showed MHC class I positivity along sarcolemma, dermatomyositis showed intense cytoplasmic positivity in perifascicular regenerating fibres, and all dystrophies except regenerating fibres were negative, with no false positives.
MHC class II deficiency is an autosomal recessive immunodeficiency. A review of 179 patients reported worldwide over ten years found extreme vulnerability to infections: respiratory infection in 82% (146/178) and gastrointestinal infection in 76% (135/178). Common laboratory findings included hypogammaglobulinemia and CD4+ lymphopenia in 93% (107/115). Diagnosis relies on flow cytometry and genetic analysis. The disease can coexist with autoimmune disorders, and one case report described an 8-month-old boy with repeated fever, immune haemolytic anaemia, severe malnutrition, and diagnosis at 20 months.
In a mouse model of graft-versus-host disease after bone marrow transplantation, complete MHC or isolated MHC class II mismatch led to significantly higher GvHD scores over time. With T-cell depletion and additional donor lymph node cell injection, isolated MHC class II mismatch caused a further increase in GvHD scores compared to MHC class I mismatch. A separate study on in-hospital cardiac arrest reporting found that case completeness in a national quality registry was 77%, with an incidence of 2.9 per 1000 hospital admissions.
What is still missing: no clinical trial has tested a drug specifically for MHC class I deficiency in humans; the available data come from small, retrospective myositis cohorts and animal models. No patient stratification by genetic or immunological subtype has been attempted in a treatment trial. Funding for a dedicated trial in primary MHC class I deficiency remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2017 · 39 citations
Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology
AbstractOBJECTIVE: To determine the clinical features of myositis patients with the histopathologic finding of CD8-positive T cells invading non-necrotic muscle fibers expressing major histocompatibility complex class 1 (CD8-MHC-1 complex), which is shared by polymyositis (PM) and inclusion body myositis (IBM), in relation to the p62 immunostaining pattern of muscle fibers. METHODS: All 93 myositis patients with CD8-MHC-1 complex who were referred to our hospital from 1993 to 2015 were classified on the basis of the European Neuromuscular Center (ENMC) diagnostic criteria for IBM (Rose, 2013) or PM (Hoogendijk, 2004) and analyzed. RESULTS: The 93 patients included were 17 patients with PM, 70 patients with IBM, and 6 patients who neither met the criteria for PM nor IBM in terms of muscle weakness distribution (unclassifiable group). For these PM, IBM, and unclassifiable patients, their mean ages at diagnosis were 63, 70, and 64 years; autoimmune disease was present in 7 (41%), 13 (19%), and 4 (67%); hepatitis C virus infection was detected in 0%, 13 (20%), and 2 (33%); and p62 was immunopositive in 0%, 66 (94%), and 2 (33%), respectively. Of the treated patients, 11 of 16 PM patients and 4 of 6 p62-immunonegative patients in the unclassifiable group showed responses to immunotherapy, whereas all 44 patients with IBM and 2 p62-immunopositive patients in the unclassifiable group were unresponsive to immunotherapy. CONCLUSIONS: CD8-MHC-1 complex is present in patients with PM, IBM, or unclassifiable group. The data may serve as an argument for a trial of immunosuppressive treatment in p62-immunonegative patients with unclassifiable myositis.
New England Journal of Medicine · 1995 · 31 citations · open access
Twin Boys with Major Histocompatibility Complex Class II Deficiency but Inducible Immune Responses
AbstractThe major histocompatibility complex (MHC) class II molecules are composed of two polypeptide chains (α and β). In humans the three distinct isotypes are designated HLA-DR, DP, and DQ. The different isotypes serve similar functions, and their expression on cells is regulated in coordinated fashion.1 MHC class II molecules are expressed on the surface of certain cells of the immune system, such as monocytes and macrophages, B cells, and dendritic cells, where they play an important part in the immune response.2 MHC class II deficiency is an autosomal recessive disease characterized by cellular and humoral immunodeficiency.3 Family studies show that . . .
Neurology India · 2008 · 22 citations · open access
Major histocompatibility complex class I expression can be used as a diagnostic tool to differentiate idiopathic inflammatory myopathies from dystrophies
AbstractAIM: Utility of major histocompatibility complex (MHC) Class I antigen immunostaining was studied to differentiate idiopathic inflammatory myopathies from dystrophies. MATERIALS AND METHODS: Forty muscle biopsies including seven dermatomyositis (DM), six polymyositis (PM), two sporadic inclusion body myositis (sIBM), 20 dystrophies (one Duchenne, three Becker's, four alpha, one gamma sarcoglycanopathy, nine limb girdle, one myotonic and one fascioscapulohumeral muscular dystrophy) and five controls were stained with antibody for MHC Class I antigen (Novocastra clone W6/32 HL 1:100 dilution). RESULTS: Polymyositis and sIBM showed MHC class I antigen positivity along sarcolemma of single and small groups of muscle fibers. The regenerating fibers in the perifascicular area in DM showed intense cytoplasmic positivity of MHC class I antigen. Muscle fibers in all dystrophies except regenerating fibers and control normal muscle were negative for MHC. Capillaries and lymphocytes were positive controls. There were no false positives in the study. CONCLUSION: MHC Class I immunostaining can be used as a complementary diagnostic tool for the diagnosis of idiopathic inflammatory myopathies.
Incidence and case ascertainment of treated in-hospital cardiac arrest events in a national quality registry – A comparison of reported and non-reported events
AbstractBACKGROUND: Approximately 2500 in-hospital cardiac arrest (IHCA) events are reported annually to the Swedish Registry of Cardiopulmonary Resuscitation (SRCR) with an estimated incidence of 1.7/1000 hospital admissions. The aim of this study was to evaluate the compliance in reporting IHCA events to the SRCR and to compare reported IHCA events with possible non-reported events, and to estimate IHCA incidence. METHODS: Fifteen diagnose codes, eight Classification of Care Measure codes, and two perioperative complication codes were used to find all treated IHCAs in 2018-2019 at six hospitals of varying sizes and resources. All identified IHCA events were cross-checked against the SRCR using personal identity numbers. All non-reported IHCA events were retrospectively reported and compared with the prospectively reported events. RESULTS: A total of 3638 hospital medical records were reviewed and 1109 IHCA events in 999 patients were identified, with 254 of the events not found in the SRCR. The case completeness was 77% (range 55-94%). IHCA incidence was 2.9/1000 hospital admissions and 12.4/1000 admissions to intensive care units. The retrospectively reported events were more often found on monitored wards, involved patients who were younger, had less comorbidity, were often found in shockable rhythm and more often achieved sustained spontaneous circulation, compared with in prospectively reported events. CONCLUSION: IHCA case completeness in the SRCR was 77% and IHCA incidence was 2.9/1000 hospital admissions. The retrospectively reported IHCA events were found in monitored areas where the rapid response team was not alerted, which might have affected regular reporting procedures.
[A major histocompatibility complex class Ⅱ deficiency case report and literature review].
AbstractOBJECTIVE: To summarize and report the clinical characteristics and laboratory results of a case and those reported in literature with MHC class Ⅱ deficiency. METHOD: The clinical features, laboratory results and gene mutation analysis of an infant with MHC class Ⅱ deficiency, who was diagnosed and treated in Peking Union Medical College Hospital since December 2013, were retrospectively analyzed."Major histocompatibility complex class Ⅱ deficiency"or"bare lymphocyte syndrome"were used as keywords in order to retrieve reports from CNKI (from its establishment to October 2015) and Wanfang Database (from its establishment to October 2015), PubMed Database (from its establishment to October 2015) was searched. The characteristics, diagnosis, treatment and prognosis were summarized by reviewing related articles. RESULT: The patient was a 8-month-old boy. Since the fourth month of life, he started to have repeated fever, susceptible to a variety of pathogens, immune hemolytic anemia, severe malnutrition, and finally diagnosed as MHC class Ⅱ deficiency disease when he was 20-month-old.No related reports were retrieved from CNKI and Wanfang database, there were 20 articles and 179 patients were reported worldwide in the past 10 years. Patients exhibit an extreme vulnerability to infections(resptratory infection(82%, 146/178), inpection of gastroin testinal(76%, 135/178)). The common laboratory examinations showed hypogammaglobulinemia, CD4(+) lymphopenia(93%, 107/115) etc. Diagnosis relies on the flow-cytometric analysis and genetic analysis. CONCLUSION: It is considered necessary for patients with young onset age, manifestation of clinically opportunistic infection as immune deficient disease, including the MHC class Ⅱ deficiency disease, especially long-term diarrhea, poor development and cryptosporidium infection. This disease could coexist with autoimmune disorders.
GvHD scores after TBI (10 Gy) and BMT across different MHC disparities.
Abstract<p>(A) After BMT (with T-cell depletion) complete MHC or isolated MHC class II mismatch led to significantly higher GvHD scores over the course of time. (B) After BMT without T-cell depletion and additional donor lymph node cell injection a further increase of GvHD scores was observed in case of isolated mismatch of MHC class II as opposed to mismatch of MHC class I.</p>
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.
