T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency

Publication Date:
2018-11-30
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Immunobiology and Immunotherapy
Published by:
http://www.hematology.org/
_version_ 1836399094033022976
autor Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
beschreibung ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper–immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α–directed migration. Gene transfer of ARPC1B in patients’ T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8 + T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.
citation_standardnr 6362172
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-11-30
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/132/22/2362?rss=1
schlagwort Immunobiology and Immunotherapy
search_space articles
shingle_author_1 Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
shingle_author_2 Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
shingle_author_3 Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
shingle_author_4 Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
shingle_catch_all_1 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
Immunobiology and Immunotherapy
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper–immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α–directed migration. Gene transfer of ARPC1B in patients’ T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8 + T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.
Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
Immunobiology and Immunotherapy
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper–immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α–directed migration. Gene transfer of ARPC1B in patients’ T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8 + T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.
Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
Immunobiology and Immunotherapy
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper–immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α–directed migration. Gene transfer of ARPC1B in patients’ T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8 + T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.
Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
Immunobiology and Immunotherapy
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper–immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α–directed migration. Gene transfer of ARPC1B in patients’ T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8 + T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.
Brigida, I., Zoccolillo, M., Cicalese, M. P., Pfajfer, L., Barzaghi, F., Scala, S., Oleaga-Quintas, C., Alvarez-Alvarez, J. A., Sereni, L., Giannelli, S., Sartirana, C., Dionisio, F., Pavesi, L., Benavides-Nieto, M., Basso-Ricci, L., Capasso, P., Mazzi, B., Rosain, J., Marcus, N., Lee, Y. N., Somech, R., Degano, M., Raiola, G., Caorsi, R., Picco, P., Moncada Velez, M., Khourieh, J., Arias, A. A., Bousfiha, A., Issekutz, T., Issekutz, A., Boisson, B., Dobbs, K., Villa, A., Lombardo, A., Neven, B., Moshous, D., Casanova, J.-L., Franco, J. L., Notarangelo, L. D., Scielzo, C., Volpi, S., Dupre, L., Bustamante, J., Gattorno, M., Aiuti, A.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
shingle_title_2 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
shingle_title_3 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
shingle_title_4 T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
timestamp 2025-06-30T23:37:30.444Z
titel T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
titel_suche T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
topic W
WW-YZ
uid ipn_articles_6362172