Therapeutic options for CTLA-4 Insufficiency
Standard
Therapeutic options for CTLA-4 Insufficiency. / Egg, David; Rump, Ina Caroline; Mitsuiki, Noriko; Rojas-Restrepo, Jessica; Maccari, Maria-Elena; Schwab, Charlotte; Gabrysch, Annemarie; Warnatz, Klaus; Goldacker, Sigune; Patiño, Virginia; Wolff, Daniel; Okada, Satoshi; Hayakawa, Seiichi; Shikama, Yoshiaki; Kanda, Kenji; Imai, Kohsuke; Sotomatsu, Manabu; Kuwashima, Makoto; Kamiya, Takahiro; Morio, Tomohiro; Matsumoto, Kazuaki; Mori, Takeshi; Yoshimoto, Yuri; Dybedal, Ingunn; Kanariou, Maria; Kucuk, Zeynep Yesim; Chapdelaine, Hugo; Petruzelkova, Lenka; Lorenz, Hanns-Martin; Sullivan, Kathleen E; Heimall, Jennifer; Moutschen, Michel; Litzman, Jiri; Recher, Mike; Albert, Michael H; Hauck, Fabian; Seneviratne, Suranjith; Schmid, Jana Pachlopnik; Kolios, Antonios; Unglik, Gary; Klemann, Christian; Snapper, Scott; Giulino-Roth, Lisa; Svaton, Michael; Platt, Craig D; Hambleton, Sophie; Neth, Olaf; Gosse, Geraldine; Reinsch, Steffen; Holzinger, Dirk; Kim, Yae-Jean; Bakhtiar, Shahrzad; Atschekzei, Faranaz; Schmidt, Reinhold; Sogkas, Georgios; Chandrakasan, Shanmuganathan; Rae, William; Derfalvi, Beata; Marquart, Hanne Vibeke; Ozen, Ahmet; Kiykim, Ayca; Karakoc-Aydiner, Elif; Králíčková, Pavlína; de Bree, Godelieve; Kiritsi, Dimitra; Seidel, Markus G; Kobbe, Robin; Dantzer, Jennifer; Alsina, Laia; Armangue, Thais; Lougaris, Vassilios; Agyeman, Philipp; Nyström, Sofia; Buchbinder, David; Arkwright, Peter D; Grimbacher, Bodo.
in: J ALLERGY CLIN IMMUN, Jahrgang 149, Nr. 2, 02.2022, S. 736-746.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Therapeutic options for CTLA-4 Insufficiency
AU - Egg, David
AU - Rump, Ina Caroline
AU - Mitsuiki, Noriko
AU - Rojas-Restrepo, Jessica
AU - Maccari, Maria-Elena
AU - Schwab, Charlotte
AU - Gabrysch, Annemarie
AU - Warnatz, Klaus
AU - Goldacker, Sigune
AU - Patiño, Virginia
AU - Wolff, Daniel
AU - Okada, Satoshi
AU - Hayakawa, Seiichi
AU - Shikama, Yoshiaki
AU - Kanda, Kenji
AU - Imai, Kohsuke
AU - Sotomatsu, Manabu
AU - Kuwashima, Makoto
AU - Kamiya, Takahiro
AU - Morio, Tomohiro
AU - Matsumoto, Kazuaki
AU - Mori, Takeshi
AU - Yoshimoto, Yuri
AU - Dybedal, Ingunn
AU - Kanariou, Maria
AU - Kucuk, Zeynep Yesim
AU - Chapdelaine, Hugo
AU - Petruzelkova, Lenka
AU - Lorenz, Hanns-Martin
AU - Sullivan, Kathleen E
AU - Heimall, Jennifer
AU - Moutschen, Michel
AU - Litzman, Jiri
AU - Recher, Mike
AU - Albert, Michael H
AU - Hauck, Fabian
AU - Seneviratne, Suranjith
AU - Schmid, Jana Pachlopnik
AU - Kolios, Antonios
AU - Unglik, Gary
AU - Klemann, Christian
AU - Snapper, Scott
AU - Giulino-Roth, Lisa
AU - Svaton, Michael
AU - Platt, Craig D
AU - Hambleton, Sophie
AU - Neth, Olaf
AU - Gosse, Geraldine
AU - Reinsch, Steffen
AU - Holzinger, Dirk
AU - Kim, Yae-Jean
AU - Bakhtiar, Shahrzad
AU - Atschekzei, Faranaz
AU - Schmidt, Reinhold
AU - Sogkas, Georgios
AU - Chandrakasan, Shanmuganathan
AU - Rae, William
AU - Derfalvi, Beata
AU - Marquart, Hanne Vibeke
AU - Ozen, Ahmet
AU - Kiykim, Ayca
AU - Karakoc-Aydiner, Elif
AU - Králíčková, Pavlína
AU - de Bree, Godelieve
AU - Kiritsi, Dimitra
AU - Seidel, Markus G
AU - Kobbe, Robin
AU - Dantzer, Jennifer
AU - Alsina, Laia
AU - Armangue, Thais
AU - Lougaris, Vassilios
AU - Agyeman, Philipp
AU - Nyström, Sofia
AU - Buchbinder, David
AU - Arkwright, Peter D
AU - Grimbacher, Bodo
N1 - Copyright © 2021. Published by Elsevier Inc.
PY - 2022/2
Y1 - 2022/2
N2 - BACKGROUND: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness.OBJECTIVE: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level.METHODS: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated.RESULTS: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed.CONCLUSION: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.
AB - BACKGROUND: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness.OBJECTIVE: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level.METHODS: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated.RESULTS: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed.CONCLUSION: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.
U2 - 10.1016/j.jaci.2021.04.039
DO - 10.1016/j.jaci.2021.04.039
M3 - SCORING: Journal article
C2 - 34111452
VL - 149
SP - 736
EP - 746
JO - J ALLERGY CLIN IMMUN
JF - J ALLERGY CLIN IMMUN
SN - 0091-6749
IS - 2
ER -