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; ... (2021). Therapeutic options for CTLA-4 insufficiency. (In Press). The Journal of allergy and clinical immunology Elsevier 10.1016/j.jaci.2021.04.039

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Infectiology

UniBE Contributor:

Agyeman, Philipp Kwame Abayie

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1097-6825

Publisher:

Elsevier

Language:

English

Submitter:

Christoph Aebi

Date Deposited:

29 Jul 2021 17:53

Last Modified:

29 Jul 2021 21:10

Publisher DOI:

10.1016/j.jaci.2021.04.039

PubMed ID:

34111452

Uncontrolled Keywords:

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

BORIS DOI:

10.48350/157805

URI:

https://boris.unibe.ch/id/eprint/157805

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