Egg, David and Rump, Ina Caroline and Mitsuiki, Noriko and Rojas-Restrepo, Jessica and Maccari, Maria-Elena and Schwab, Charlotte and Gabrysch, Annemarie and Warnatz, Klaus and Goldacker, Sigune and Patino, Virginia and Wolff, Daniel and Okada, Satoshi and Hayakawa, Seiichi and Shikama, Yoshiaki and Kanda, Kenji and Imai, Kohsuke and Sotomatsu, Manabu and Kuwashima, Makoto and Kamiya, Takahiro and Morio, Tomohiro and Matsumoto, Kazuaki and Mori, Takeshi and Yoshimoto, Yuri and Dybedal, Ingunn and Kanariou, Maria and Kucuk, Zeynep Yesim and Chapdelaine, Hugo and Petruzelkova, Lenka and Lorenz, Hanns-Martin and Sullivan, Kathleen E. and Heimall, Jennifer and Moutschen, Michel and Litzman, Jiri and Recher, Mike and Albert, Michael H. and Hauck, Fabian and Seneviratne, Suranjith and Schmid, Jana Pachlopnik and Kolios, Antonios and Unglik, Gary and Klemann, Christian and Snapper, Scott and Giulino-Roth, Lisa and Svaton, Michael and Platt, Craig D. and Hambleton, Sophie and Neth, Olaf and Gosse, Geraldine and Reinsch, Steffen and Holzinger, Dirk and Kim, Yae-Jean and Bakhtiar, Shahrzad and Atschekzei, Faranaz and Schmidt, Reinhold and Sogkas, Georgios and Chandrakasan, Shanmuganathan and Rae, William and Derfalvi, Beata and Marquart, Hanne Vibeke and Ozen, Ahmet and Kiykim, Ayca and Karakoc-Aydiner, Elif and Kralickova, Pavlina and de Bree, Godelieve and Kiritsi, Dimitra and Seidel, Markus G. and Kobbe, Robin and Dantzer, Jennifer and Alsina, Laia and Armangue, Thais and Lougaris, Vassilios and Agyeman, Philipp and Nystrom, Sofia and Buchbinder, David and Arkwright, Peter D. and Grimbacher, Bodo (2022) Therapeutic options for CTLA-4 insufficiency. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 149 (2). pp. 736-746. ISSN 0091-6749, 1097-6825
Full text not available from this repository. (Request a copy)Abstract
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: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNE DYSREGULATION; MANAGEMENT; RITUXIMAB; DEFICIENCY; MUTATIONS; DISEASE; CTLA-4; common variable immunodeficiency; primary immunodeficiency; diagnosis; treatment; abatacept; sirolimus; LRBA; rituximab; HSCT |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Dec 2023 15:09 |
| Last Modified: | 11 Dec 2023 15:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58853 |
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