DOI . ORG {
}
Title[redir]:
Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity | Journal of Clinical Immunology
Description:
Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.
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Keywords {🔍}
patients, article, iei, variants, pubmed, google, scholar, molecular, diagnosis, genetic, clinical, adult, immunol, sequencing, immune, syndrome, group, gene, cas, autoimmune, immunity, dysregulation, study, fig, diseases, immunodeficiency, somatic, inborn, errors, signs, due, warning, patient, clin, disorders, diagnostic, primary, lymphoproliferative, ngs, variant, deficiency, hospital, allergy, wmoldx, germline, human, identified, targeted, phenotype, years,
Topics {✒️}
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headline:Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity
description:Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.
datePublished:2024-02-16T00:00:00Z
dateModified:2024-02-16T00:00:00Z
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autoimmunity
germline variants
human inborn errors of immunity (IEI)
infections
Jeffrey model foundation warning signs
immune dysregulation
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NGS
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Immunology
Infectious Diseases
Internal Medicine
Medical Microbiology
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headline:Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity
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infections
Jeffrey model foundation warning signs
immune dysregulation
lymphoproliferation
NGS
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somatic variants
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Medical Microbiology
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name:Research Institute Hospital
address:
name:Research Institute Hospital, Madrid, Spain
type:PostalAddress
type:Organization
name:Complutense University of Madrid
address:
name:School of Medicine, Complutense University of Madrid, Madrid, Spain
type:PostalAddress
type:Organization
name:University Hospital
address:
name:Unit of Immunodeficiencies, Department of Pediatrics, University Hospital, Madrid, Spain
type:PostalAddress
type:Organization
name:Juan F. Quesada-Espinosa
affiliation:
name:Research Institute Hospital
address:
name:Research Institute Hospital, Madrid, Spain
type:PostalAddress
type:Organization
name:University Hospital
address:
name:Department of Genetics, University Hospital, Madrid, Spain
type:PostalAddress
type:Organization
name:Luis M. Allende
url:http://orcid.org/0000-0001-9586-8539
affiliation:
name:University Hospital
address:
name:Department of Immunology, University Hospital, Madrid, Spain
type:PostalAddress
type:Organization
name:Research Institute Hospital
address:
name:Research Institute Hospital, Madrid, Spain
type:PostalAddress
type:Organization
name:Complutense University of Madrid
address:
name:School of Medicine, Complutense University of Madrid, Madrid, Spain
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:School of Medicine, Complutense University of Madrid, Madrid, Spain
name:Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
name:Department of Internal Medicine, University Hospital, Madrid, Spain
name:Unit of Immunology, University Hospital General Dr Balmis, Alicante, Spain
name:Department of Immunology, University Hospital Fundación Jiménez Díaz, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:School of Medicine, Complutense University of Madrid, Madrid, Spain
name:Unit of Immunodeficiencies, Department of Pediatrics, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:Department of Genetics, University Hospital, Madrid, Spain
name:Department of Immunology, University Hospital, Madrid, Spain
name:Research Institute Hospital, Madrid, Spain
name:School of Medicine, Complutense University of Madrid, Madrid, Spain
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