Therapeutic options for CTLA-4 insufficiency

J 2022

Therapeutic options for CTLA-4 insufficiency

EGG, D., I. C. RUMP, N. MITSUIKI, J. ROJAS-RESTREPO, M. E. MACCARI et. al.

Basic information

Original name

Therapeutic options for CTLA-4 insufficiency

Authors

EGG, D., I. C. RUMP, N. MITSUIKI, J. ROJAS-RESTREPO, M. E. MACCARI, C. SCHWAB, A. GABRYSCH, K. WARNATZ, S. GOLDACKER, V. PATIÑO, D. WOLFF, S. OKADA, S. HAYAKAWA, Y. SHIKAMA, K. KANDA, K. IMAI, M. SOTOMATSU, M. KUWASHIMA, T. KAMIYA, T. MORIO, K. MATSUMOTO, T. MORI, Y. YOSHIMOTO, I. DYBEDAL, M. KANARIOU, Z. Y. KUCUK, H. CHAPDELAINE, L. PETRUZELKOVA, H. M. LORENZ, K. E. SULLIVAN, J. HEIMALL, M. MOUTSCHEN, Jiří LITZMAN (203 Czech Republic, belonging to the institution), M. RECHER, M. H. ALBERT, F. HAUCK, S. SENEVIRATNE, J. PACHLOPNIK SCHMID, A. KOLIOS, G. UNGLIK, C. KLEMANN, S. SNAPPER, L. GIULINO-ROTH, Michael SVATON (203 Czech Republic), C. D. PLATT, S. HAMBLETON, O. NETH, G. GOSSE, S. REINSCH, D. HOLZINGER, Y. J. KIM, S. BAKHTIAR, F. ATSCHEKZEI, R. SCHMIDT, G. SOGKAS, S. CHANDRAKASAN, W. RAE, B. DERFALVI, H. V. MARQUART, A. OZEN, A. KIYKIM, E. KARAKOC-AYDINER, P. KRÁLÍČKOVÁ, G. DE BREE, D. KIRITSI, M. G. SEIDEL, R. KOBBE, J. DANTZER, L. ALSINA, T. ARMANGUE, V. LOUGARIS, P. AGYEMAN, S. NYSTRÖM, D. BUCHBINDER, P. D. ARKWRIGHT and B. GRIMBACHER (guarantor)

Edition

Journal of Allergy and Clinical Immunology, New York, Mosby-Elseiver, 2022, 0091-6749

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 14.200

RIV identification code

RIV/00216224:14110/22:00125671

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.jaci.2021.04.039

UT WoS

000752623200031

Keywords in English

CTLA-4; HSCT; LRBA; abatacept; common variable immunodeficiency; diagnosis; primary immunodeficiency; rituximab; sirolimus; treatment

Abstract

V originále

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.

Citovat

EGG, D., I. C. RUMP, N. MITSUIKI, J. ROJAS-RESTREPO, M. E. MACCARI, C. SCHWAB, A. GABRYSCH, K. WARNATZ, S. GOLDACKER, V. PATIÑO, D. WOLFF, S. OKADA, S. HAYAKAWA, Y. SHIKAMA, K. KANDA, K. IMAI, M. SOTOMATSU, M. KUWASHIMA, T. KAMIYA, T. MORIO, K. MATSUMOTO, T. MORI, Y. YOSHIMOTO, I. DYBEDAL, M. KANARIOU, Z. Y. KUCUK, H. CHAPDELAINE, L. PETRUZELKOVA, H. M. LORENZ, K. E. SULLIVAN, J. HEIMALL, M. MOUTSCHEN, Jiří LITZMAN, M. RECHER, M. H. ALBERT, F. HAUCK, S. SENEVIRATNE, J. PACHLOPNIK SCHMID, A. KOLIOS, G. UNGLIK, C. KLEMANN, S. SNAPPER, L. GIULINO-ROTH, Michael SVATON, C. D. PLATT, S. HAMBLETON, O. NETH, G. GOSSE, S. REINSCH, D. HOLZINGER, Y. J. KIM, S. BAKHTIAR, F. ATSCHEKZEI, R. SCHMIDT, G. SOGKAS, S. CHANDRAKASAN, W. RAE, B. DERFALVI, H. V. MARQUART, A. OZEN, A. KIYKIM, E. KARAKOC-AYDINER, P. KRÁLÍČKOVÁ, G. DE BREE, D. KIRITSI, M. G. SEIDEL, R. KOBBE, J. DANTZER, L. ALSINA, T. ARMANGUE, V. LOUGARIS, P. AGYEMAN, S. NYSTRÖM, D. BUCHBINDER, P. D. ARKWRIGHT and B. GRIMBACHER. Therapeutic options for CTLA-4 insufficiency. Journal of Allergy and Clinical Immunology. New York: Mosby-Elseiver, 2022, vol. 149, No 2, p. 736-746. ISSN 0091-6749. Available from: https://dx.doi.org/10.1016/j.jaci.2021.04.039.

@article{1847092,
   author = {Egg, D. and Rump, I. C. and Mitsuiki, N. and RojasandRestrepo, J. and Maccari, M. E. and Schwab, C. and Gabrysch, A. and Warnatz, K. and Goldacker, S. and Patiño, V. and Wolff, D. and Okada, S. and Hayakawa, S. and Shikama, Y. and Kanda, K. and Imai, K. and Sotomatsu, M. and Kuwashima, M. and Kamiya, T. and Morio, T. and Matsumoto, K. and Mori, T. and Yoshimoto, Y. and Dybedal, I. and Kanariou, M. and Kucuk, Z. Y. and Chapdelaine, H. and Petruzelkova, L. and Lorenz, H. M. and Sullivan, K. E. and Heimall, J. and Moutschen, M. and Litzman, Jiří and Recher, M. and Albert, M. H. and Hauck, F. and Seneviratne, S. and Pachlopnik Schmid, J. and Kolios, A. and Unglik, G. and Klemann, C. and Snapper, S. and GiulinoandRoth, L. and Svaton, Michael and Platt, C. D. and Hambleton, S. and Neth, O. and Gosse, G. and Reinsch, S. and Holzinger, D. and Kim, Y. J. and Bakhtiar, S. and Atschekzei, F. and Schmidt, R. and Sogkas, G. and Chandrakasan, S. and Rae, W. and Derfalvi, B. and Marquart, H. V. and Ozen, A. and Kiykim, A. and KarakocandAydiner, E. and Králíčková, P. and de Bree, G. and Kiritsi, D. and Seidel, M. G. and Kobbe, R. and Dantzer, J. and Alsina, L. and Armangue, T. and Lougaris, V. and Agyeman, P. and Nyström, S. and Buchbinder, D. and Arkwright, P. D. and Grimbacher, B.},
   article_location = {New York},
   article_number = {2},
   doi = {http://dx.doi.org/10.1016/j.jaci.2021.04.039},
   keywords = {CTLA-4; HSCT; LRBA; abatacept; common variable immunodeficiency; diagnosis; primary immunodeficiency; rituximab; sirolimus; treatment},
   language = {eng},
   issn = {0091-6749},
   journal = {Journal of Allergy and Clinical Immunology},
   title = {Therapeutic options for CTLA-4 insufficiency},
   url = {https://www.sciencedirect.com/science/article/pii/S0091674921008915?via%3Dihub},
   volume = {149},
   year = {2022}
}

TY  - JOUR
ID  - 1847092
AU  - Egg, D. - Rump, I. C. - Mitsuiki, N. - Rojas-Restrepo, J. - Maccari, M. E. - Schwab, C. - Gabrysch, A. - Warnatz, K. - Goldacker, S. - Patiño, V. - Wolff, D. - Okada, S. - Hayakawa, S. - Shikama, Y. - Kanda, K. - Imai, K. - Sotomatsu, M. - Kuwashima, M. - Kamiya, T. - Morio, T. - Matsumoto, K. - Mori, T. - Yoshimoto, Y. - Dybedal, I. - Kanariou, M. - Kucuk, Z. Y. - Chapdelaine, H. - Petruzelkova, L. - Lorenz, H. M. - Sullivan, K. E. - Heimall, J. - Moutschen, M. - Litzman, Jiří - Recher, M. - Albert, M. H. - Hauck, F. - Seneviratne, S. - Pachlopnik Schmid, J. - Kolios, A. - Unglik, G. - Klemann, C. - Snapper, S. - Giulino-Roth, L. - Svaton, Michael - Platt, C. D. - Hambleton, S. - Neth, O. - Gosse, G. - Reinsch, S. - Holzinger, D. - Kim, Y. J. - Bakhtiar, S. - Atschekzei, F. - Schmidt, R. - Sogkas, G. - Chandrakasan, S. - Rae, W. - Derfalvi, B. - Marquart, H. V. - Ozen, A. - Kiykim, A. - Karakoc-Aydiner, E. - Králíčková, P. - de Bree, G. - Kiritsi, D. - Seidel, M. G. - Kobbe, R. - Dantzer, J. - Alsina, L. - Armangue, T. - Lougaris, V. - Agyeman, P. - Nyström, S. - Buchbinder, D. - Arkwright, P. D. - Grimbacher, B.
PY  - 2022
TI  - Therapeutic options for CTLA-4 insufficiency
JF  - Journal of Allergy and Clinical Immunology
VL  - 149
IS  - 2
SP  - 736-746
EP  - 736-746
PB  - Mosby-Elseiver
SN  - 00916749
KW  - CTLA-4
KW  - HSCT
KW  - LRBA
KW  - abatacept
KW  - common variable immunodeficiency
KW  - diagnosis
KW  - primary immunodeficiency
KW  - rituximab
KW  - sirolimus
KW  - treatment
UR  - https://www.sciencedirect.com/science/article/pii/S0091674921008915?via%3Dihub
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.
ER  -

EGG, D., I. C. RUMP, N. MITSUIKI, J. ROJAS-RESTREPO, M. E. MACCARI, C. SCHWAB, A. GABRYSCH, K. WARNATZ, S. GOLDACKER, V. PATIÑO, D. WOLFF, S. OKADA, S. HAYAKAWA, Y. SHIKAMA, K. KANDA, K. IMAI, M. SOTOMATSU, M. KUWASHIMA, T. KAMIYA, T. MORIO, K. MATSUMOTO, T. MORI, Y. YOSHIMOTO, I. DYBEDAL, M. KANARIOU, Z. Y. KUCUK, H. CHAPDELAINE, L. PETRUZELKOVA, H. M. LORENZ, K. E. SULLIVAN, J. HEIMALL, M. MOUTSCHEN, Jiří LITZMAN, M. RECHER, M. H. ALBERT, F. HAUCK, S. SENEVIRATNE, J. PACHLOPNIK SCHMID, A. KOLIOS, G. UNGLIK, C. KLEMANN, S. SNAPPER, L. GIULINO-ROTH, Michael SVATON, C. D. PLATT, S. HAMBLETON, O. NETH, G. GOSSE, S. REINSCH, D. HOLZINGER, Y. J. KIM, S. BAKHTIAR, F. ATSCHEKZEI, R. SCHMIDT, G. SOGKAS, S. CHANDRAKASAN, W. RAE, B. DERFALVI, H. V. MARQUART, A. OZEN, A. KIYKIM, E. KARAKOC-AYDINER, P. KRÁLÍČKOVÁ, G. DE BREE, D. KIRITSI, M. G. SEIDEL, R. KOBBE, J. DANTZER, L. ALSINA, T. ARMANGUE, V. LOUGARIS, P. AGYEMAN, S. NYSTRÖM, D. BUCHBINDER, P. D. ARKWRIGHT and B. GRIMBACHER. Therapeutic options for CTLA-4 insufficiency. \textit{Journal of Allergy and Clinical Immunology}. New York: Mosby-Elseiver, 2022, vol.~149, No~2, p.~736-746. ISSN~0091-6749. Available from: https://dx.doi.org/10.1016/j.jaci.2021.04.039.

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