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Vivien Béziat @vbeziat.bsky.social · 09/01/2026

6/ This argues for stronger dialogue in clinical immunology (and other medical fields) between patient-based and population-based genetics —biology and medicine sit at their intersection.

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Vivien Béziat @vbeziat.bsky.social · 09/01/2026

5/ Practical consequences in the field of clinical immunology at large: 🔹 For clinical genetics: stop using frequency as an exclusion criterion. 🔹 For population genetics: common variants deserve mechanistic and clinical follow-up —in “monogenic” frameworks they can have large effect.

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Vivien Béziat @vbeziat.bsky.social · 09/01/2026

4/ We compile and discuss examples of common variants across 14 immunity genes, illustrating how they can cause or shape monogenic disorders with high or low penetrance.

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Vivien Béziat @vbeziat.bsky.social · 09/01/2026

3/ Pathogenicity should be evaluated through functional impact, penetrance, and context, not MAF thresholds alone.

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Vivien Béziat @vbeziat.bsky.social · 09/01/2026

2/ “Monogenic” ≠ “rare.” Allele frequency is a population metric — not a proxy for biological or medical impact.

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Vivien Béziat @vbeziat.bsky.social · 09/01/2026

🧬 New in @cellpress.bsky.social 🧵 1/ With @casanovalab.bsky.social , we propose a rethinking of monogenic disorders of immunity: 👉 common variants can matter — a lot.

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Vivien Béziat @vbeziat.bsky.social · 06/06/2025

Thank you to all the fantastic collaborators involved in this story. @casanovalab.bsky.social, and all not on bluesky, in particular Marie Materna, Simin Seyedpour, Tom Le Voyer, Nima Parvaneh, Niloufar Yazdanpanah, Jacinta Bustamante, Mohammad Shahrooei and Nima Rezaie

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Vivien Béziat @vbeziat.bsky.social · 06/06/2025

Please consider submitting your work to @jhumimmunity.org, the novel journal of the “Inborn Error of Immunity” community. It is published by the nonprofit @rupress.org

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Vivien Béziat @vbeziat.bsky.social · 06/06/2025

🧩 Conclusion: The absence of ⍺β T cells is sufficient to cause SCID. γδ T cells and other leukocytes cannot compensate for this loss.

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Vivien Béziat @vbeziat.bsky.social · 06/06/2025

🧬 Our molecular data show: • New variants = complete loss-of-function → total absence of ⍺β T cells • Original c.+1G>A variant = partial loss-of-function → low TCR⍺β expression & unconventional ⍺β T cells, explaining longer survival without transplant

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Vivien Béziat @vbeziat.bsky.social · 06/06/2025

In our study, we report 2 patients from unrelated families with novel TCR⍺ variants. Unlike earlier cases, they presented with severe combined immunodeficiency and early, life-threatening infections.

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Vivien Béziat @vbeziat.bsky.social · 06/06/2025

This suggested that lacking ⍺β T cells results “only” in combined immunodeficiency (CID), not severe combined immunodeficiency (SCID)—likely due to compensation by γδ T cells.

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Vivien Béziat @vbeziat.bsky.social · 06/06/2025

Previously, TCR⍺ deficiency was reported in 5 patients from 3 kindreds, all carrying the same variant (c.+1G>A). Despite the absence of conventional ⍺β T cells, these patients survived into childhood without early transplant. 📖 www.jci.org/articles/vie...

jci.org

JCI - Mutation in the TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ+ T cells

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Reposted by Vivien Béziat

Journal of Human Immunity @jhumimmunity.org · 04/06/2025

Materna, @vbeziat.bsky.social‬ et al. @institutimagine.bsky.social‬ report children with complete TCRα deficiency, a lack of αβ T cells, & a severe condition. Previously characterized TCRα deficiency, which wasn't as severe as expected, was partial, as opposed to complete rupress.org/jhi/article/...

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Reposted by Vivien Béziat

Rockefeller University Press @rupress.org · 04/06/2025

New in @jhumimmunity.org: Materna, @vbeziat.bsky.social‬ et al. report children with complete TCRα deficiency, a lack of αβ T cells, & a severe condition. Previously characterized TCRα deficiency, which wasn't as severe as expected, was partial, as opposed to complete rupress.org/jhi/article/...

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