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Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay
Published on: September 7, 2018
Inherited human TFIIIA deficiency disrupts T cell development
Evi Duthoo1,2,3, Sueun Park1,2, Tamara Jarayseh1,2
1Primary Immunodeficiency Research Lab (PIRL), Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Medrxiv : the Preprint Server for Health Sciences
|July 10, 2026
Summary
Rare genetic variants in GTF3A cause TFIIIA deficiency, leading to severe combined immunodeficiency (SCID) and combined immune deficiency (CID). This discovery highlights TFIIIA
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Inborn errors of T cell immunity offer biological insights and medical advancements.
- Understanding the genetic basis of severe combined immunodeficiency (SCID) and combined immune deficiency (CID) is crucial for developing effective treatments.
Purpose of the Study:
- To identify the genetic cause of (S)CID in patients with T cell lymphopenia.
- To elucidate the molecular mechanisms underlying TFIIIA deficiency in human adaptive immunity.
Main Methods:
- Whole-exome sequencing to identify deleterious variants in GTF3A.
- Functional assays including DNA binding, nuclear localization, and protein stability studies.
- In vitro studies using artificial thymic organoids and in vivo studies in zebrafish models.
Main Results:
- Identified biallelic deleterious GTF3A variants in ten patients from eight families with (S)CID.
- Demonstrated that GTF3A variants impair TFIIIA function, affecting 5S rRNA transcription and chaperoning.
- Observed early developmental arrest in T cell commitment in TFIIIA-deficient models.
Conclusions:
- TFIIIA deficiency is a novel monogenic cause of (S)CID.
- TFIIIA plays an essential role in human T cell development and adaptive immunity.
- This finding expands the genetic landscape of primary immunodeficiencies.
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