Therapeutic options for CTLA-4 insufficiency.
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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, Pachlopnik Schmid Jana, 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
Аннотация
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.