This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Kuehn HS, Ouyang W, Lo B, Deenick EK, Niemela JE, Avery DT, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science. 2014;345(6204):1623–7.
Schubert D, Bode C, Kenefeck R, Hou TZ, Wing JB, Kennedy A, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med. 2014;20(12):1410–6.
Schwab C, Gabrysch A, Olbrich P, Patino V, Warnatz K, Wolff D, et al. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. J Allergy Clin Immunol. 2018;142(6):1932–46.
Lo B, Fritz JM, Su HC, Uzel G, Jordan MB, Lenardo MJ. CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency. Blood. 2016;128(8):1037–42.
Serwas NK, Hoeger B, Ardy RC, Stulz SV, Sui Z, Memaran N, et al. Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis. Nat Commun. 2019;10(1):3106.
Egg D, Schwab C, Gabrysch A, Arkwright PD, Cheesman E, Giulino-Roth L, et al. Increased risk for malignancies in 131 affected CTLA4 mutation carriers. Front Immunol. 2018;9:2012.
Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. Kaposi sarcoma. Nature Reviews Disease Primers. 2019;5(1):9.
Weiss L, Roux A, Garcia S, Demouchy C, Haeffner-Cavaillon N, Kazatchkine MD, et al. Persistent expansion, in a human immunodeficiency virus-infected person, of V beta-restricted CD4+CD8+ T lymphocytes that express cytotoxicity-associated molecules and are committed to produce interferon-gamma and tumor necrosis factor-alpha. J Infect Dis. 1998;178(4):1158–62.
Colombatti A, Doliana R, Schiappacassi M, Argentini C, Tonutti E, Feruglio C, et al. Age-related persistent clonal expansions of CD28(−) cells: phenotypic and molecular TCR analysis reveals both CD4(+) and CD4(+)CD8(+) cells with identical CDR3 sequences. Clin Immunol Immunopathol. 1998;89(1):61–70.
Tangye SG, Al-Herz W, Bousfiha A, Chatila T, Cunningham-Rundles C, Etzioni A, et al. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2020.
Hou TZ, Verma N, Wanders J, Kennedy A, Soskic B, Janman D, et al. Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations. Blood. 2017;129(11):1458–68.
Li YI, Knowles DA, Humphrey J, Barbeira AN, Dickinson SP, Im HK, et al. Annotation-free quantification of RNA splicing using LeafCutter. Nat Genet. 2018;50(1):151–8.
Sterne-Weiler T, Weatheritt RJ, Best AJ, Ha KCH, Blencowe BJ. Efficient and accurate quantitative profiling of alternative splicing patterns of any complexity on a laptop. Mol Cell. 2018;72(1):187–200 e6.
Peach RJ, Bajorath J, Brady W, Leytze G, Greene J, Naemura J, et al. Complementarity determining region 1 (CDR1)- and CDR3-analogous regions in CTLA-4 and CD28 determine the binding to B7-1. J Exp Med. 1994;180(6):2049–58.
Leiding JW, Forbes LR. Mechanism-based precision therapy for the treatment of primary immunodeficiency and primary immunodysregulatory diseases. J Allergy Clin Immunol Pract. 2019;7(3):761–73.
Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol. 2006;177(12):8338–47.
Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, et al. Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med. 2005;352(13):1317–23.
Basu G, Mohapatra A, Manipadam MT, Mani SE, John GT. Leflunomide with low-dose everolimus for treatment of Kaposi’s sarcoma in a renal allograft recipient. Nephrol Dial Transplant. 2011;26(10):3412–5.
Rukasz D, Krajewska M, Augustyniak-Bartosik H, Letachowicz K, Halon A, Ekiert M, et al. Effective treatment of Kaposi sarcoma with everolimus in a patient with membranous glomerulonephritis. Intern Med J. 2015;45(2):230–1.
Mourah S, Porcher R, Battistella M, Kerob D, Guillot B, Jouary T, et al. Paradoxical simultaneous regression and progression of lesions in a phase II study of everolimus in classic Kaposi sarcoma. Br J Dermatol. 2015;173(5):1284–7.
Garcia-Perez JE, Baxter RM, Kong DS, Tobin R, McCarter M, Routes JM, et al. CTLA4 message reflects pathway disruption in monogenic disorders and under therapeutic blockade. Front Immunol. 2019;10:998.
Lougaris V, Tabellini G, Baronio M, Patrizi O, Gazzurelli L, Mitsuiki N, et al. CTLA-4 regulates human natural killer cell effector functions. Clin Immunol. 2018;194:43–5.
We thank the John Brown Cook Foundation, Jeffrey Modell Foundation, UNSW Triple I SPHERE Clinically Accredited Group, NSW Office of Health and Medical Research, St Vincent’s Clinic Foundation, Allergy and Immunodeficiency Foundation of Australia (AIFA), Garvan-Weizmann Foundation, the David Cooper Memorial Fund, and NHMRC grant ID1155678 for grant support. This work was supported in part with federal funds from the Frederick National Laboratory for Cancer Research, under contract number HHSN261200800001E and NCI contract 75N91019D00024.
Conflict of Interest
The authors declare that they have no conflicts of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yap, J.Y., Gloss, B., Batten, M. et al. Everolimus-Induced Remission of Classic Kaposi’s Sarcoma Secondary to Cryptic Splicing Mediated CTLA4 Haploinsufficiency. J Clin Immunol 40, 774–779 (2020). https://doi.org/10.1007/s10875-020-00804-8