The immunopathological landscape of human pre-TCRa deficiency: From rare to common variants

Marie Materna; Ottavia M. Delmonte; Marita Bosticardo; Mana Momenilandi; Peyton E. Conrey; Bénédicte Charmeteau De Muylder; Clotilde Bravetti; Rebecca Bellworthy; Axel Cederholm; Frederik Staels; Christian A. Ganoza; Samuel Darko; Samir Sayed; Corentin Le Floc’h; Masato Ogishi; Darawan Rinchai; Andrea Guenoun; Alexandre Bolze; Taushif Khan; Adrian Gervais; Renate Krüger; Mirjam Völler; Boaz Palterer; Mahnaz Sadeghi-Shabestari; Anne Langlois de Septenville; Chaim A. Schramm; Sanjana Shah; John J. Tello-Cajiao; Francesca Pala; Kayla Amini; Jose S. Campos; Noemia Santana Lima; Daniel Eriksson; Romain Lévy; Yoann Seeleuthner; Soma Jyonouchi; Manar Ata; Fatima Al Ali; Caroline Deswarte; Anaïs Pereira; Jérôme Mégret; Tom Le Voyer; Paul Bastard; Laureline Berteloot; Michaël Dussiot; Natasha Vladikine; Paula P. Cardenas; Emmanuelle Jouanguy; Mashael Alqahtani; Amal Hasan; Thangavel Alphonse Thanaraj; Jérémie Rosain; Fahd Al Qureshah; Vito Sabato; Marie Alexandra Alyanakian; Marianne Leruez-Ville; Flore Rozenberg; Elie Haddad; Jose R. Regueiro; Maria L. Toribio; Judith R. Kelsen; Mansoor Salehi; Shahram Nasiri; Mehdi Torabizadeh; Hassan Rokni-Zadeh; Majid Changi-Ashtiani; Nasimeh Vatandoost; Hossein Moravej; Seyed Mohammad Akrami; Mohsen Mazloomrezaei; Aurélie Cobat; Isabelle Meyts; Etsushi Toyofuku; Madoka Nishimura; Kunihiko Moriya; Tomoyuki Mizukami; Kohsuke Imai; Laurent Abel; Bernard Malissen; Fahd Al-Mulla; Fowzan Sami Alkuraya; Nima Parvaneh; Horst von Bernuth; Christian Beetz; Frédéric Davi; Daniel C. Douek; Rémi Cheynier; David Langlais; Nils Landegren; Nico Marr; Tomohiro Morio; Mohammad Shahrooei; Rik Schrijvers; Sarah E. Henrickson; Hervé Luche; Luigi D. Notarangelo; Jean Laurent Casanova; Vivien Béziat

doi:10.1126/science.adh4059

The immunopathological landscape of human pre-TCRa deficiency: From rare to common variants

Marie Materna, Ottavia M. Delmonte, Marita Bosticardo, Mana Momenilandi, Peyton E. Conrey, Bénédicte Charmeteau De Muylder, Clotilde Bravetti, Rebecca Bellworthy, Axel Cederholm, Frederik Staels, Christian A. Ganoza, Samuel Darko, Samir Sayed, Corentin Le Floc’h, Masato Ogishi, Darawan Rinchai, Andrea Guenoun, Alexandre Bolze, Taushif Khan, Adrian GervaisRenate Krüger, Mirjam Völler, Boaz Palterer, Mahnaz Sadeghi-Shabestari, Anne Langlois de Septenville, Chaim A. Schramm, Sanjana Shah, John J. Tello-Cajiao, Francesca Pala, Kayla Amini, Jose S. Campos, Noemia Santana Lima, Daniel Eriksson, Romain Lévy, Yoann Seeleuthner, Soma Jyonouchi, Manar Ata, Fatima Al Ali, Caroline Deswarte, Anaïs Pereira, Jérôme Mégret, Tom Le Voyer, Paul Bastard, Laureline Berteloot, Michaël Dussiot, Natasha Vladikine, Paula P. Cardenas, Emmanuelle Jouanguy, Mashael Alqahtani, Amal Hasan, Thangavel Alphonse Thanaraj, Jérémie Rosain, Fahd Al Qureshah, Vito Sabato, Marie Alexandra Alyanakian, Marianne Leruez-Ville, Flore Rozenberg, Elie Haddad, Jose R. Regueiro, Maria L. Toribio, Judith R. Kelsen, Mansoor Salehi, Shahram Nasiri, Mehdi Torabizadeh, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Nasimeh Vatandoost, Hossein Moravej, Seyed Mohammad Akrami, Mohsen Mazloomrezaei, Aurélie Cobat, Isabelle Meyts, Etsushi Toyofuku, Madoka Nishimura, Kunihiko Moriya, Tomoyuki Mizukami, Kohsuke Imai, Laurent Abel, Bernard Malissen, Fahd Al-Mulla, Fowzan Sami Alkuraya, Nima Parvaneh, Horst von Bernuth, Christian Beetz, Frédéric Davi, Daniel C. Douek, Rémi Cheynier, David Langlais, Nils Landegren, Nico Marr, Tomohiro Morio, Mohammad Shahrooei, Rik Schrijvers, Sarah E. Henrickson, Hervé Luche, Luigi D. Notarangelo, Jean Laurent Casanova, Vivien Béziat

Research output: Contribution to journal › Article › peer-review

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Abstract

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-a T cell receptor (pre-TCRa) expression. Low circulating naive a|! T cell counts at birth persisted over time, with normal memory a|>, and high _T5 T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue aft T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive aft T cell counts but high yS T cell counts. Although residual pre-TCRa expression drove the differentiation of more ap T cells, autoimmune conditions were more frequent in these patients compared with the general population.

Original language	English
Article number	adh4059
Journal	Science
Volume	383
Issue number	6686
DOIs	https://doi.org/10.1126/science.adh4059
State	Published - 1 Mar 2024

Funding Agency

Kuwait Foundation for the Advancement of Sciences

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10.1126/science.adh4059

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Materna, M., Delmonte, O. M., Bosticardo, M., Momenilandi, M., Conrey, P. E., Muylder, B. C. D., Bravetti, C., Bellworthy, R., Cederholm, A., Staels, F., Ganoza, C. A., Darko, S., Sayed, S., Floc’h, C. L., Ogishi, M., Rinchai, D., Guenoun, A., Bolze, A., Khan, T., ... Béziat, V. (2024). The immunopathological landscape of human pre-TCRa deficiency: From rare to common variants. Science, 383(6686), Article adh4059. https://doi.org/10.1126/science.adh4059

@article{8087217a252649649d9b1ab35b8910b6,

title = "The immunopathological landscape of human pre-TCRa deficiency: From rare to common variants",

abstract = "We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-a T cell receptor (pre-TCRa) expression. Low circulating naive a|! T cell counts at birth persisted over time, with normal memory a|>, and high T5 T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue aft T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive aft T cell counts but high yS T cell counts. Although residual pre-TCRa expression drove the differentiation of more ap T cells, autoimmune conditions were more frequent in these patients compared with the general population.",

author = "Marie Materna and Delmonte, {Ottavia M.} and Marita Bosticardo and Mana Momenilandi and Conrey, {Peyton E.} and Muylder, {B{\'e}n{\'e}dicte Charmeteau De} and Clotilde Bravetti and Rebecca Bellworthy and Axel Cederholm and Frederik Staels and Ganoza, {Christian A.} and Samuel Darko and Samir Sayed and Floc{\textquoteright}h, {Corentin Le} and Masato Ogishi and Darawan Rinchai and Andrea Guenoun and Alexandre Bolze and Taushif Khan and Adrian Gervais and Renate Kr{\"u}ger and Mirjam V{\"o}ller and Boaz Palterer and Mahnaz Sadeghi-Shabestari and {de Septenville}, {Anne Langlois} and Schramm, {Chaim A.} and Sanjana Shah and Tello-Cajiao, {John J.} and Francesca Pala and Kayla Amini and Campos, {Jose S.} and Lima, {Noemia Santana} and Daniel Eriksson and Romain L{\'e}vy and Yoann Seeleuthner and Soma Jyonouchi and Manar Ata and Ali, {Fatima Al} and Caroline Deswarte and Ana{\"i}s Pereira and J{\'e}r{\^o}me M{\'e}gret and {Le Voyer}, Tom and Paul Bastard and Laureline Berteloot and Micha{\"e}l Dussiot and Natasha Vladikine and Cardenas, {Paula P.} and Emmanuelle Jouanguy and Mashael Alqahtani and Amal Hasan and Thanaraj, {Thangavel Alphonse} and J{\'e}r{\'e}mie Rosain and Qureshah, {Fahd Al} and Vito Sabato and Alyanakian, {Marie Alexandra} and Marianne Leruez-Ville and Flore Rozenberg and Elie Haddad and Regueiro, {Jose R.} and Toribio, {Maria L.} and Kelsen, {Judith R.} and Mansoor Salehi and Shahram Nasiri and Mehdi Torabizadeh and Hassan Rokni-Zadeh and Majid Changi-Ashtiani and Nasimeh Vatandoost and Hossein Moravej and Akrami, {Seyed Mohammad} and Mohsen Mazloomrezaei and Aur{\'e}lie Cobat and Isabelle Meyts and Etsushi Toyofuku and Madoka Nishimura and Kunihiko Moriya and Tomoyuki Mizukami and Kohsuke Imai and Laurent Abel and Bernard Malissen and Fahd Al-Mulla and Alkuraya, {Fowzan Sami} and Nima Parvaneh and {von Bernuth}, Horst and Christian Beetz and Fr{\'e}d{\'e}ric Davi and Douek, {Daniel C.} and R{\'e}mi Cheynier and David Langlais and Nils Landegren and Nico Marr and Tomohiro Morio and Mohammad Shahrooei and Rik Schrijvers and Henrickson, {Sarah E.} and Herv{\'e} Luche and Notarangelo, {Luigi D.} and Casanova, {Jean Laurent} and Vivien B{\'e}ziat",

year = "2024",

month = mar,

day = "1",

doi = "10.1126/science.adh4059",

language = "English",

volume = "383",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6686",

}

Materna, M, Delmonte, OM, Bosticardo, M, Momenilandi, M, Conrey, PE, Muylder, BCD, Bravetti, C, Bellworthy, R, Cederholm, A, Staels, F, Ganoza, CA, Darko, S, Sayed, S, Floc’h, CL, Ogishi, M, Rinchai, D, Guenoun, A, Bolze, A, Khan, T, Gervais, A, Krüger, R, Völler, M, Palterer, B, Sadeghi-Shabestari, M, de Septenville, AL, Schramm, CA, Shah, S, Tello-Cajiao, JJ, Pala, F, Amini, K, Campos, JS, Lima, NS, Eriksson, D, Lévy, R, Seeleuthner, Y, Jyonouchi, S, Ata, M, Ali, FA, Deswarte, C, Pereira, A, Mégret, J, Le Voyer, T, Bastard, P, Berteloot, L, Dussiot, M, Vladikine, N, Cardenas, PP, Jouanguy, E, Alqahtani, M, Hasan, A, Thanaraj, TA, Rosain, J, Qureshah, FA, Sabato, V, Alyanakian, MA, Leruez-Ville, M, Rozenberg, F, Haddad, E, Regueiro, JR, Toribio, ML, Kelsen, JR, Salehi, M, Nasiri, S, Torabizadeh, M, Rokni-Zadeh, H, Changi-Ashtiani, M, Vatandoost, N, Moravej, H, Akrami, SM, Mazloomrezaei, M, Cobat, A, Meyts, I, Toyofuku, E, Nishimura, M, Moriya, K, Mizukami, T, Imai, K, Abel, L, Malissen, B, Al-Mulla, F, Alkuraya, FS, Parvaneh, N, von Bernuth, H, Beetz, C, Davi, F, Douek, DC, Cheynier, R, Langlais, D, Landegren, N, Marr, N, Morio, T, Shahrooei, M, Schrijvers, R, Henrickson, SE, Luche, H, Notarangelo, LD, Casanova, JL & Béziat, V 2024, 'The immunopathological landscape of human pre-TCRa deficiency: From rare to common variants', Science, vol. 383, no. 6686, adh4059. https://doi.org/10.1126/science.adh4059

TY - JOUR

T1 - The immunopathological landscape of human pre-TCRa deficiency

T2 - From rare to common variants

AU - Materna, Marie

AU - Delmonte, Ottavia M.

AU - Bosticardo, Marita

AU - Momenilandi, Mana

AU - Conrey, Peyton E.

AU - Muylder, Bénédicte Charmeteau De

AU - Bravetti, Clotilde

AU - Bellworthy, Rebecca

AU - Cederholm, Axel

AU - Staels, Frederik

AU - Ganoza, Christian A.

AU - Darko, Samuel

AU - Sayed, Samir

AU - Floc’h, Corentin Le

AU - Ogishi, Masato

AU - Rinchai, Darawan

AU - Guenoun, Andrea

AU - Bolze, Alexandre

AU - Khan, Taushif

AU - Gervais, Adrian

AU - Krüger, Renate

AU - Völler, Mirjam

AU - Palterer, Boaz

AU - Sadeghi-Shabestari, Mahnaz

AU - de Septenville, Anne Langlois

AU - Schramm, Chaim A.

AU - Shah, Sanjana

AU - Tello-Cajiao, John J.

AU - Pala, Francesca

AU - Amini, Kayla

AU - Campos, Jose S.

AU - Lima, Noemia Santana

AU - Eriksson, Daniel

AU - Lévy, Romain

AU - Seeleuthner, Yoann

AU - Jyonouchi, Soma

AU - Ata, Manar

AU - Ali, Fatima Al

AU - Deswarte, Caroline

AU - Pereira, Anaïs

AU - Mégret, Jérôme

AU - Le Voyer, Tom

AU - Bastard, Paul

AU - Berteloot, Laureline

AU - Dussiot, Michaël

AU - Vladikine, Natasha

AU - Cardenas, Paula P.

AU - Jouanguy, Emmanuelle

AU - Alqahtani, Mashael

AU - Hasan, Amal

AU - Thanaraj, Thangavel Alphonse

AU - Rosain, Jérémie

AU - Qureshah, Fahd Al

AU - Sabato, Vito

AU - Alyanakian, Marie Alexandra

AU - Leruez-Ville, Marianne

AU - Rozenberg, Flore

AU - Haddad, Elie

AU - Regueiro, Jose R.

AU - Toribio, Maria L.

AU - Kelsen, Judith R.

AU - Salehi, Mansoor

AU - Nasiri, Shahram

AU - Torabizadeh, Mehdi

AU - Rokni-Zadeh, Hassan

AU - Changi-Ashtiani, Majid

AU - Vatandoost, Nasimeh

AU - Moravej, Hossein

AU - Akrami, Seyed Mohammad

AU - Mazloomrezaei, Mohsen

AU - Cobat, Aurélie

AU - Meyts, Isabelle

AU - Toyofuku, Etsushi

AU - Nishimura, Madoka

AU - Moriya, Kunihiko

AU - Mizukami, Tomoyuki

AU - Imai, Kohsuke

AU - Abel, Laurent

AU - Malissen, Bernard

AU - Al-Mulla, Fahd

AU - Alkuraya, Fowzan Sami

AU - Parvaneh, Nima

AU - von Bernuth, Horst

AU - Beetz, Christian

AU - Davi, Frédéric

AU - Douek, Daniel C.

AU - Cheynier, Rémi

AU - Langlais, David

AU - Landegren, Nils

AU - Marr, Nico

AU - Morio, Tomohiro

AU - Shahrooei, Mohammad

AU - Schrijvers, Rik

AU - Henrickson, Sarah E.

AU - Luche, Hervé

AU - Notarangelo, Luigi D.

AU - Casanova, Jean Laurent

AU - Béziat, Vivien

PY - 2024/3/1

Y1 - 2024/3/1

N2 - We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-a T cell receptor (pre-TCRa) expression. Low circulating naive a|! T cell counts at birth persisted over time, with normal memory a|>, and high T5 T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue aft T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive aft T cell counts but high yS T cell counts. Although residual pre-TCRa expression drove the differentiation of more ap T cells, autoimmune conditions were more frequent in these patients compared with the general population.

AB - We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-a T cell receptor (pre-TCRa) expression. Low circulating naive a|! T cell counts at birth persisted over time, with normal memory a|>, and high T5 T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue aft T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive aft T cell counts but high yS T cell counts. Although residual pre-TCRa expression drove the differentiation of more ap T cells, autoimmune conditions were more frequent in these patients compared with the general population.

UR - http://www.scopus.com/inward/record.url?scp=85186292695&partnerID=8YFLogxK

U2 - 10.1126/science.adh4059

DO - 10.1126/science.adh4059

M3 - Article

C2 - 38422122

AN - SCOPUS:85186292695

SN - 0036-8075

VL - 383

JO - Science

JF - Science

IS - 6686

M1 - adh4059

ER -

The immunopathological landscape of human pre-TCRa deficiency: From rare to common variants

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