Advances and highlights in primary immunodeficiencies in 2017

Area of Science:

• Immunology
• Genetics
• Hematology

Background:

• Primary immunodeficiency diseases (PIDDs) encompass a heterogeneous group of genetic disorders affecting the immune system.
• Understanding the pathogenesis of PIDDs is crucial for developing effective diagnostic and therapeutic strategies.
• Recent research has shed light on various aspects of PIDDs, from cellular mechanisms to novel genetic defects.

Purpose of the Study:

• To review key advancements in the understanding and management of primary immunodeficiency diseases (PIDDs) published in 2017.
• To highlight progress in areas such as B-cell differentiation, signaling pathways, autoimmune manifestations, and genetic underpinnings of PIDDs.
• To summarize the latest therapeutic interventions, including stem cell transplantation, gene therapy, and gene editing, for various PIDDs.

Main Methods:

• Literature review of selected topics in primary immunodeficiency diseases (PIDDs) published in 2017.
• Synthesis of findings related to T-cell and B-cell function, signaling pathways, and autoimmune phenomena in PIDDs.
• Compilation of data on newly identified gene defects and the efficacy of emerging therapies like gene editing and transplantation.

Main Results:

• Identified the role of follicular T cells in B-cell differentiation and antibody responses.
• Revealed impaired nuclear factor κB subunit 1 signaling in common variable immunodeficiency, linking B-cell maturation defects to inflammation.
• Described new gene defects (EXTL3, TNFAIP3, ARPC1B, RELA, HYOU1, BACH2, CD70, CD55) associated with PIDDs.
• Demonstrated improved outcomes (90% 2-year survival) in hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID) due to early diagnosis and screening.
• Showcased the efficacy of lentiviral gene therapy for adenosine deaminase-deficient SCID and the promise of gene editing (CRISPR/Cas9, ZFN) for SCID and chronic granulomatous disease.
• Reported the efficacy of thymus transplantation in Europe, alongside an unexpected high incidence of autoimmunity.

Conclusions:

• Significant progress has been made in understanding the pathogenesis and genetic basis of PIDDs.
• Novel therapeutic strategies, including gene therapy and gene editing, offer promising avenues for treating severe forms of PIDDs.
• Early diagnosis through newborn screening and advancements in transplantation have dramatically improved outcomes for conditions like SCID.
• Continued research in PIDDs is essential for improving patient care and developing more targeted treatments.