Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia

Roshini S. Abraham; Amrita Basu; Jennifer R. Heimall; Elizabeth Dunn; Alison Yip; Malika Kapadia; Neena Kapoor; Lisa Forbes Satter; Rebecca Buckley; Richard O'Reilly; Geoffrey D.E. Cuvelier; Sharat Chandra; Jeffrey Bednarski; Sonali Chaudhury; Theodore B. Moore; Hilary Haines; Blachy J. Dávila Saldaña; Deepakbabu Chellapandian; Ahmad Rayes; Karin Chen; Emi Caywood; Shanmuganathan Chandrakasan; Mark Thomas Vander Lugt; Christen Ebens; Pierre Teira; Evan Shereck; Holly Miller; Victor Aquino; Hesham Eissa; Lolie C. Yu; Alfred Gillio; Lisa Madden; Alan Knutsen; Ami J. Shah; Kenneth DeSantes; Jessie Barnum; Larisa Broglie; Avni Y. Joshi; Gary Kleiner; Jasmeen Dara; Susan Prockop; Caridad Martinez; Talal Mousallem; Joseph Oved; Lauri Burroughs; Rebecca Marsh; Troy R. Torgerson; Jennifer W. Leiding; Sung Yun Pai; Donald B. Kohn; Michael A. Pulsipher; Linda M. Griffith; Luigi D. Notarangelo; Morton J. Cowan; Jennifer Puck; Christopher C. Dvorak; Elie Haddad

doi:10.1016/j.clim.2024.109942

Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia

Roshini S. Abraham^*, Amrita Basu, Jennifer R. Heimall, Elizabeth Dunn, Alison Yip, Malika Kapadia, Neena Kapoor, Lisa Forbes Satter, Rebecca Buckley, Richard O'Reilly, Geoffrey D.E. Cuvelier, Sharat Chandra, Jeffrey Bednarski, Sonali Chaudhury, Theodore B. Moore, Hilary Haines, Blachy J. Dávila Saldaña, Deepakbabu Chellapandian, Ahmad Rayes, Karin ChenEmi Caywood, Shanmuganathan Chandrakasan, Mark Thomas Vander Lugt, Christen Ebens, Pierre Teira, Evan Shereck, Holly Miller, Victor Aquino, Hesham Eissa, Lolie C. Yu, Alfred Gillio, Lisa Madden, Alan Knutsen, Ami J. Shah, Kenneth DeSantes, Jessie Barnum, Larisa Broglie, Avni Y. Joshi, Gary Kleiner, Jasmeen Dara, Susan Prockop, Caridad Martinez, Talal Mousallem, Joseph Oved, Lauri Burroughs, Rebecca Marsh, Troy R. Torgerson, Jennifer W. Leiding, Sung Yun Pai, Donald B. Kohn, Michael A. Pulsipher, Linda M. Griffith, Luigi D. Notarangelo, Morton J. Cowan, Jennifer Puck, Christopher C. Dvorak, Elie Haddad

^*Corresponding author for this work

Pediatrics

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

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Abstract

Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.02). Further, in patients with CD3+ T cell counts between 51 and 300 cells/μL, there was a higher proliferative response with the PHA flow assay compared to the ³H-T assay (p < 0.0001), suggesting that the method of analysis influences the resolution and interpretation of PHA results. Importantly, we observed many SCID patients with profound T cell lymphopenia having normal T cell proliferation when assessed by flow cytometry. We recommend this test be considered only as supportive in the diagnosis of typical SCID.

Original language	English (US)
Article number	109942
Journal	Clinical Immunology
Volume	261
DOIs	https://doi.org/10.1016/j.clim.2024.109942
State	Published - Apr 2024

Funding

This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID), and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) grant U54A1082973, MPI: JMP, CCD, EH; grants U54NS064808 and U01TR001263, PI: JP Krischer). The content and opinions expressed are solely the responsibility of the authors and do not represent the official policy and positions of the funding agencies and sponsors.SYP is supported by funding from the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research. EH is supported by The Bank of Montreal Research Chair in Pediatric Immunology. JRH is supported by the Elizabeth Paige Lavin Endowed Chair in Immunology and Clinical Care. LDN is supported by funding from the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health. MJC is supported by the California Institute of Regenerative Medicine (CIRM, CLIN2-10830) and NIAID-NIH U54-AI082973). MAP is supported by 1U01AI126612-01A1, P30CA040214, and 2UG1HL069254.RSA has been on the advisory board for Horizon Pharma (now Amgen) and Sobi in the past 2 years but is not currently serving in that capacity.RM is an employee of Pharming Healthcare Inc., Warren, NJ.JWL is an employee and shareholder of Bluebird Bio, and has been a speaker/consultant and on the advisory board for Sobi, Inc. This work was supported by the Division of Allergy, Immunology and Transplantation , National Institute of Allergy and Infectious Diseases (NIAID), and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) grant U54A1082973 , MPI: JMP, CCD, EH ; grants U54NS064808 and U01TR001263 , PI: JP Krischer ). The content and opinions expressed are solely the responsibility of the authors and do not represent the official policy and positions of the funding agencies and sponsors. SYP is supported by funding from the Intramural Research Program , National Institutes of Health , National Cancer Institute , Center for Cancer Research . EH is supported by The Bank of Montreal Research Chair in Pediatric Immunology . JRH is supported by the Elizabeth Paige Lavin Endowed Chair in Immunology and Clinical Care . LDN is supported by funding from the Intramural Research Program , National Institute of Allergy and Infectious Diseases , National Institutes of Health . MJC is supported by the California Institute of Regenerative Medicine (CIRM, CLIN2-10830 ) and NIAID-NIH U54-AI082973 ). MAP is supported by 1U01AI126612-01A1 , P30CA040214 , and 2UG1HL069254 .

Keywords

Mitogen
PHA
PIDTC
SCID
Severe combined immunodeficiency
T-cell lymphopenia
T-cell proliferation

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.clim.2024.109942

Cite this

Abraham, R. S., Basu, A., Heimall, J. R., Dunn, E., Yip, A., Kapadia, M., Kapoor, N., Satter, L. F., Buckley, R., O'Reilly, R., Cuvelier, G. D. E., Chandra, S., Bednarski, J., Chaudhury, S., Moore, T. B., Haines, H., Dávila Saldaña, B. J., Chellapandian, D., Rayes, A., ... Haddad, E. (2024). Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia. Clinical Immunology, 261, Article 109942. https://doi.org/10.1016/j.clim.2024.109942

@article{cf6715c3927b4fe5aeb33b1eee912a7a,

title = "Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia",

abstract = "Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.02). Further, in patients with CD3+ T cell counts between 51 and 300 cells/μL, there was a higher proliferative response with the PHA flow assay compared to the 3H-T assay (p < 0.0001), suggesting that the method of analysis influences the resolution and interpretation of PHA results. Importantly, we observed many SCID patients with profound T cell lymphopenia having normal T cell proliferation when assessed by flow cytometry. We recommend this test be considered only as supportive in the diagnosis of typical SCID.",

keywords = "Mitogen, PHA, PIDTC, SCID, Severe combined immunodeficiency, T-cell lymphopenia, T-cell proliferation",

author = "Abraham, {Roshini S.} and Amrita Basu and Heimall, {Jennifer R.} and Elizabeth Dunn and Alison Yip and Malika Kapadia and Neena Kapoor and Satter, {Lisa Forbes} and Rebecca Buckley and Richard O'Reilly and Cuvelier, {Geoffrey D.E.} and Sharat Chandra and Jeffrey Bednarski and Sonali Chaudhury and Moore, {Theodore B.} and Hilary Haines and {D{\'a}vila Salda{\~n}a}, {Blachy J.} and Deepakbabu Chellapandian and Ahmad Rayes and Karin Chen and Emi Caywood and Shanmuganathan Chandrakasan and Lugt, {Mark Thomas Vander} and Christen Ebens and Pierre Teira and Evan Shereck and Holly Miller and Victor Aquino and Hesham Eissa and Yu, {Lolie C.} and Alfred Gillio and Lisa Madden and Alan Knutsen and Shah, {Ami J.} and Kenneth DeSantes and Jessie Barnum and Larisa Broglie and Joshi, {Avni Y.} and Gary Kleiner and Jasmeen Dara and Susan Prockop and Caridad Martinez and Talal Mousallem and Joseph Oved and Lauri Burroughs and Rebecca Marsh and Torgerson, {Troy R.} and Leiding, {Jennifer W.} and Pai, {Sung Yun} and Kohn, {Donald B.} and Pulsipher, {Michael A.} and Griffith, {Linda M.} and Notarangelo, {Luigi D.} and Cowan, {Morton J.} and Jennifer Puck and Dvorak, {Christopher C.} and Elie Haddad",

note = "Publisher Copyright: {\textcopyright} 2024 Elsevier Inc.",

year = "2024",

month = apr,

doi = "10.1016/j.clim.2024.109942",

language = "English (US)",

volume = "261",

journal = "Clinical Immunology",

issn = "1521-6616",

publisher = "Academic Press Inc.",

}

Abraham, RS, Basu, A, Heimall, JR, Dunn, E, Yip, A, Kapadia, M, Kapoor, N, Satter, LF, Buckley, R, O'Reilly, R, Cuvelier, GDE, Chandra, S, Bednarski, J, Chaudhury, S, Moore, TB, Haines, H, Dávila Saldaña, BJ, Chellapandian, D, Rayes, A, Chen, K, Caywood, E, Chandrakasan, S, Lugt, MTV, Ebens, C, Teira, P, Shereck, E, Miller, H, Aquino, V, Eissa, H, Yu, LC, Gillio, A, Madden, L, Knutsen, A, Shah, AJ, DeSantes, K, Barnum, J, Broglie, L, Joshi, AY, Kleiner, G, Dara, J, Prockop, S, Martinez, C, Mousallem, T, Oved, J, Burroughs, L, Marsh, R, Torgerson, TR, Leiding, JW, Pai, SY, Kohn, DB, Pulsipher, MA, Griffith, LM, Notarangelo, LD, Cowan, MJ, Puck, J, Dvorak, CC & Haddad, E 2024, 'Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia', Clinical Immunology, vol. 261, 109942. https://doi.org/10.1016/j.clim.2024.109942

TY - JOUR

T1 - Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia

AU - Abraham, Roshini S.

AU - Basu, Amrita

AU - Heimall, Jennifer R.

AU - Dunn, Elizabeth

AU - Yip, Alison

AU - Kapadia, Malika

AU - Kapoor, Neena

AU - Satter, Lisa Forbes

AU - Buckley, Rebecca

AU - O'Reilly, Richard

AU - Cuvelier, Geoffrey D.E.

AU - Chandra, Sharat

AU - Bednarski, Jeffrey

AU - Chaudhury, Sonali

AU - Moore, Theodore B.

AU - Haines, Hilary

AU - Dávila Saldaña, Blachy J.

AU - Chellapandian, Deepakbabu

AU - Rayes, Ahmad

AU - Chen, Karin

AU - Caywood, Emi

AU - Chandrakasan, Shanmuganathan

AU - Lugt, Mark Thomas Vander

AU - Ebens, Christen

AU - Teira, Pierre

AU - Shereck, Evan

AU - Miller, Holly

AU - Aquino, Victor

AU - Eissa, Hesham

AU - Yu, Lolie C.

AU - Gillio, Alfred

AU - Madden, Lisa

AU - Knutsen, Alan

AU - Shah, Ami J.

AU - DeSantes, Kenneth

AU - Barnum, Jessie

AU - Broglie, Larisa

AU - Joshi, Avni Y.

AU - Kleiner, Gary

AU - Dara, Jasmeen

AU - Prockop, Susan

AU - Martinez, Caridad

AU - Mousallem, Talal

AU - Oved, Joseph

AU - Burroughs, Lauri

AU - Marsh, Rebecca

AU - Torgerson, Troy R.

AU - Leiding, Jennifer W.

AU - Pai, Sung Yun

AU - Kohn, Donald B.

AU - Pulsipher, Michael A.

AU - Griffith, Linda M.

AU - Notarangelo, Luigi D.

AU - Cowan, Morton J.

AU - Puck, Jennifer

AU - Dvorak, Christopher C.

AU - Haddad, Elie

PY - 2024/4

Y1 - 2024/4

N2 - Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.02). Further, in patients with CD3+ T cell counts between 51 and 300 cells/μL, there was a higher proliferative response with the PHA flow assay compared to the 3H-T assay (p < 0.0001), suggesting that the method of analysis influences the resolution and interpretation of PHA results. Importantly, we observed many SCID patients with profound T cell lymphopenia having normal T cell proliferation when assessed by flow cytometry. We recommend this test be considered only as supportive in the diagnosis of typical SCID.

AB - Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.02). Further, in patients with CD3+ T cell counts between 51 and 300 cells/μL, there was a higher proliferative response with the PHA flow assay compared to the 3H-T assay (p < 0.0001), suggesting that the method of analysis influences the resolution and interpretation of PHA results. Importantly, we observed many SCID patients with profound T cell lymphopenia having normal T cell proliferation when assessed by flow cytometry. We recommend this test be considered only as supportive in the diagnosis of typical SCID.

KW - Mitogen

KW - PHA

KW - PIDTC

KW - SCID

KW - Severe combined immunodeficiency

KW - T-cell lymphopenia

KW - T-cell proliferation

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UR - http://www.scopus.com/inward/citedby.url?scp=85185721479&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2024.109942

DO - 10.1016/j.clim.2024.109942

M3 - Article

C2 - 38367737

AN - SCOPUS:85185721479

SN - 1521-6616

VL - 261

JO - Clinical Immunology

JF - Clinical Immunology

M1 - 109942

ER -

Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia

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