Monogenic forms of common variable immunodeficiency and implications on target therapeutic approaches

Tessarin, Giulio; Baronio, Manuela; Lougaris, Vassilios

doi:10.1097/aci.0000000000000947

Cited by 3 publications

(1 citation statement)

References 56 publications

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“…However, no significant differences in CD8 Treg ratios were observed between patients with CVID with or without autoimmunity ( 109 ). Because CVID is an umbrella term for a probable heterogeneous group of diseases with different pathophysiological mechanisms ( 110 ), the study of Treg in this disease is challenging. Further research with larger series and more specific approaches are needed to fully understand the role of CD4 and CD8 Tregs in the pathogenesis and clinical manifestations of CVID and its relationship with autoimmunity.…”

Section: Iei and Treg: The New Kid On The Blockmentioning

confidence: 99%

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Kennedy-Batalla,

Acevedo,

Luo

et al. 2024

Front. Immunol.

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Regulatory T cells (Treg) are essential for immune balance, preventing overreactive responses and autoimmunity. Although traditionally characterized as CD4+CD25+CD127lowFoxP3hi, recent research has revealed diverse Treg subsets such as Tr1, Tr1-like, and CD8 Treg. Treg dysfunction leads to severe autoimmune diseases and immune-mediated inflammatory disorders. Inborn errors of immunity (IEI) are a group of disorders that affect correct functioning of the immune system. IEI include Tregopathies caused by genetic mutations affecting Treg development or function. In addition, Treg dysfunction is also observed in other IEIs, whose underlying mechanisms are largely unknown, thus requiring further research. This review provides a comprehensive overview and discussion of Treg in IEI focused on: A) advances and controversies in the evaluation of Treg extended subphenotypes and function; B) current knowledge and gaps in Treg disturbances in Tregopathies and other IEI including Treg subpopulation changes, genotype-phenotype correlation, Treg changes with disease activity, and available therapies, and C) the potential of Treg cell-based therapies for IEI with immune dysregulation. The aim is to improve both the diagnostic and the therapeutic approaches to IEI when there is involvement of Treg. We performed a non-systematic targeted literature review with a knowledgeable selection of current, high-quality original and review articles on Treg and IEI available since 2003 (with 58% of the articles within the last 6 years) in the PubMed database.

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Section: Iei and Treg: The New Kid On The Blockmentioning

confidence: 99%

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Kennedy-Batalla,

Acevedo,

Luo

et al. 2024

Front. Immunol.

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Unmasking inborn errors of immunity: identifying the red flags of immune dysregulation

Cortesi,

Dotta,

Cattalini

et al. 2024

Front. Immunol.

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Inborn errors of immunity (IEI) are rare diseases that affect the immune system. According to the latest International Union of Immunological Societies (IUIS) classification, 485 different IEI have been identified. Even if increased susceptibility to infections is the best-known symptom, IEI are no longer defined by the higher likelihood of infections alone. Immune dysregulation with autoimmune disease and hyperinflammation, lymphoproliferation, and malignancy are common manifestations and could be the only symptoms of IEI that must be recognized. An exclusive focus on infection-centered warning signs would miss around 25% of patients with IEI who initially present with other manifestations. Timely and appropriate diagnosis and treatment are essential to enhance the quality of life (QoL) and, in some cases, survival, as patients are susceptible to life-threatening infections or autoimmunity. In addition, the advantage of early diagnosis in IEI with immune dysregulation (i.e. CTLA4 deficiency, LRBA deficiency, NF-kB1/NF-kB2 deficiency, activated phosphoinositide 3-kinase delta syndrome -APDS-) is the initiation of targeted therapies with precise re-balancing of the dysregulated immune pathways (i.e., biologicals, selective inhibitors) or definitive therapy (i.e., HSCT).

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Immunogenetic Landscape in Pediatric Common Variable Immunodeficiency

Szczawińska-Popłonyk,

Ciesielska,

Konarczak

et al. 2024

IJMS

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Common variable immunodeficiency (CVID) is the most common symptomatic antibody deficiency, characterized by heterogeneous genetic, immunological, and clinical phenotypes. It is no longer conceived as a sole disease but as an umbrella diagnosis comprising a spectrum of clinical conditions, with defects in antibody biosynthesis as their common denominator and complex pathways determining B and T cell developmental impairments due to genetic defects of many receptors and ligands, activating and co-stimulatory molecules, and intracellular signaling molecules. Consequently, these genetic variants may affect crucial immunological processes of antigen presentation, antibody class switch recombination, antibody affinity maturation, and somatic hypermutation. While infections are the most common features of pediatric CVID, variants in genes linked to antibody production defects play a role in pathomechanisms of immune dysregulation with autoimmunity, allergy, and lymphoproliferation reflecting the diversity of the immunogenetic underpinnings of CVID. Herein, we have reviewed the aspects of genetics in CVID, including the monogenic, digenic, and polygenic models of inheritance exemplified by a spectrum of genes relevant to CVID pathophysiology. We have also briefly discussed the epigenetic mechanisms associated with micro RNA, DNA methylation, chromatin reorganization, and histone protein modification processes as background for CVID development.

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Monogenic forms of common variable immunodeficiency and implications on target therapeutic approaches

Cited by 3 publications

References 56 publications

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Unmasking inborn errors of immunity: identifying the red flags of immune dysregulation

Immunogenetic Landscape in Pediatric Common Variable Immunodeficiency

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