IPEX syndrome from diagnosis to cure, learning along the way

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 153(3), P. 595 - 605

Published: Nov. 30, 2023

In the past 2 decades, a significant number of studies have been published describing molecular and clinical aspects immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome. These refined our knowledge this rare yet prototypic genetic autoimmune disease, advancing diagnosis, broadening spectrum, improving understanding underlying immunologic mechanisms. Despite these advances, Forkhead box P3 mutations devastating consequences, treating patients with IPEX syndrome remains challenge, even safer strategies for hematopoietic stem cell transplantation gene therapy becoming promising reality. The aim review was to highlight novel features disease further advance awareness improve diagnosis treatment

Language: Английский

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The recombinase activating genes: architects of immune diversity during lymphocyte development

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 11, 2023

The mature lymphocyte population of a healthy individual has the remarkable ability to recognise an immense variety antigens. Instead encoding unique gene for each potential antigen receptor, evolution used rearrangements, also known as variable, diversity, and joining segment (V(D)J) recombination. This process is critical development relies on recombination-activating genes-1 (RAG1) RAG2, here collectively referred RAG. RAG serves powerful genome editing tools lymphocytes strictly regulated prevent dysregulation. However, in case dysregulation, been implicated cases cancer, autoimmunity severe combined immunodeficiency (SCID). review examines functional protein domains motifs RAG, describes advances our understanding function (dys)regulation discuss new therapeutic options, such therapy, deficiencies, explore

Language: Английский

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Gene regulation in inborn errors of immunity: Implications for gene therapy design and efficacy

Immunological Reviews, Journal Year: 2024, Volume and Issue: 322(1), P. 157 - 177

Published: Jan. 17, 2024

Summary Inborn errors of immunity (IEI) present a unique paradigm in the realm gene therapy, emphasizing need for precision therapeutic design. As therapy transitions from broad‐spectrum addition to careful modification specific genes, enduring safety and effectiveness these therapies clinical settings have become crucial. This review discusses significance IEIs as foundational models pioneering refining medicine. We explore capabilities correction platforms modifying DNA sequence primary cells tailored IEIs. The uses four highlight key issues strategies: X‐linked agammaglobulinemia (XLA), chronic granulomatous disease (X‐CGD), hyper IgM syndrome (XHIGM), immune dysregulation, polyendocrinopathy, enteropathy, (IPEX). detail regulatory intricacies innovations each disorder, incorporating insights relevant trials. For most IEIs, regulated expression is vital aspect underlying biology, we discuss importance endogenous regulation developing strategies.

Language: Английский

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Precision Reimagined: CRISPR and Multiomics Transform Systemic Lupus Erythematosus Diagnosis and Therapy

International Journal of Rheumatic Diseases, Journal Year: 2025, Volume and Issue: 28(4)

Published: April 1, 2025

ABSTRACT Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with diverse clinical manifestations and unpredictable progression, posing significant challenges to accurate diagnosis effective treatment. Traditional biomarkers treatments often fail address the disease's molecular heterogeneity. Recent advancements in CRISPR gene‐editing technology multiomics approaches offer transformative opportunities for personalized SLE care by unraveling its underlying complexity enabling precise therapeutic interventions. allows targeted editing of SLE‐associated genetic mutations, addressing disease drivers directly, while multiomics—including genomics, transcriptomics, proteomics—provides insights into dysregulated immune networks, identifying targets. Integrating these can refine patient stratification enhance precision treatments. Artificial intelligence (AI) complements technologies synthesizing high‐dimensional data, treatment plans, predicting trajectories, optimizing strategies. However, integration settings raises challenges, including technical limitations, ethical concerns, economic barriers. Emerging trials case studies demonstrate potential innovations personalize improve outcomes. Nonetheless, transition from experimental research routine application requires robust regulatory frameworks strategies challenges. This review aims explore revolutionize therapy, emphasizing their AI advance care. By existing barriers, envisions future where medicine transforms management, paving way individualized, patient‐centered therapy.

Language: Английский

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Correcting Autoinflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI) by Human Stem Cell Genome-Editing

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Type I interferonopathies comprise a large group of Mendelian autoinflammatory diseases that generally lack effective treatments. STING-associated Vasculitis with onset in Infancy (SAVI) is severe autosomal dominant disease due to gain-of-functon(GOF) mutations the gene STING1, encoding for Stimulator Interferon Response CGAMP Interactor 1 (STING1). SAVI leads multisystemic comprising systemic vasculitis and lung fibrosis. A possible therapeutic approach engineer patient’s hematopoietic system restore interferon homeostasis, thereby preventing chronic inflammation organ damage halting development. Here, we describe “universal” genome editing correction strategy using CRISPR/Cas9 targets stimulator response cGAMP interactor (STING1) at endogenous locus patient-derived induced pluripotent stem cells (iPSCs) human CD34+ progenitor (HSPCs). The engineered SAVI-iPSCs express normal levels STING1 protein following differentiation into monocytes macrophages no longer produce interferon-alpha (IFN-α) basal state. Using SAVI-gene-engineered HSPCs, determined minimum fraction mutant alleles required induce spontaneous IFN-α production, thus establishing threshold necessary rescue disease. Finally, demonstrated HSPCs retain regenerative potential by supporting long-term repopulating capacity multi-lineage transplantation immunocompromised mice. Together, these studies established rationale clinical translation framework correcting other type interferonopathies.

Language: Английский

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Must Reads for Clinicians Seeking a Better Understanding of Primary Immune Deficiency Disorders and Related Disorders

The Journal of Allergy and Clinical Immunology In Practice, Journal Year: 2023, Volume and Issue: 11(6), P. 1703 - 1705

Published: April 23, 2023

Language: Английский

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Editorial: Advances in therapeutic strategies of inborn errors of immunity

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 9, 2023

EDITORIAL article Front. Immunol., 09 November 2023Sec. Primary Immunodeficiencies Volume 14 - 2023 | https://doi.org/10.3389/fimmu.2023.1328846

Language: Английский

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