Browsing by Author "Bosticardo, Marita"

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    HSCT corrects primary immunodeficiency and immune dysregulation in patients with POMP-related auto-inflammatory disease
    (2021) Martinez, Caridad; Ebstein, Frédéric; Nicholas, Sarah K.; Guzman, Marietta De; Forbes, Lisa R.; Delmonte, Ottavia M.; Bosticardo, Marita; Castagnoli, Riccardo; Krance, Robert; Notarangelo, Luigi D.; Krüger, Elke; Orange, Jordan S.; Poli, Cecilia
    Inborn errors of immunity that present with concomitant immunodeficiency and auto-inflammation are therapeutically challenging; furthermore, complexity is added when they are caused by mutations in genes that encode for proteins expressed beyond immune cells. The ubiquitin-proteasome system is the main intracellular proteolytic machinery and participates in most cellular processes by degrading ubiquitinated proteins. Mutations in proteasome subunits resulting in proteasome deficiency cause a severe autoinflammatory disease characterized by chronic auto-inflammation neutrophilic dermatosis and fever, collectively referred to as Proteasome Associated Auto-inflammatory Syndromes (PRAAS). POMP is a chaperone for proteasome assembly and AD mutations in POMP cause a form of PRAAS with prominent immunodeficiency referred to as POMP-related auto-inflammation and immune dysregulation (PRAID) manifesting with recurrent, severe and opportunistic infections in addition to inflammatory features that are characteristic for all PRAAS disorders, most importantly early-onset neutrophilic dermatosis. JAK inhibitors partially control the disease in individuals with PRAAS, however life-threatening, recurrent and opportunistic infections in patients with POMP mutations limit immunosuppressive therapies and prompted consideration of hematopoietic stem cell transplant (HSCT). We describe successful HSCT in two patients with POMP deficiency. Despite POMP being ubiquitously expressed, the immunologic and autoinflammatory phenotype were both ameliorated through HSCT which suggests that the clinical and immunological features of PRAID are predominantly derived from a proteasome defect in hematopoietic cells. To our knowledge, these are the first patients with a form of PRAAS cured by HSCT, opening new therapeutic possibilities for these diseases.
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    Multiomics dissection of human RAG deficiency revealsdistinctive patterns of immune dysregulation but acommon inflammatory signature
    (2025) Bosticardo, Marita; Dobbs, Kerry; Delmonte, Ottavia; Martins, Andrew; Pala, Francesca; Kawai, Tomoki; Kenney, Heather; Magro, Gloria; Rosen, Lindsey; Yamazaki, Yasuhiro; Yu, Hsin-Hui; Calzoni, Enrica; Lee, Yu Nee; Liu, Can; Stoddard, Jennifer; Niemela, Julie; Fink, Danielle; Castagnoli, Riccardo; Ramba, Meredith; Cheng, Aristine; Riley, Deanna; Oikonomou, Vasileios; Shaw, Elana; Belaid, Brahim; Keles, Sevgi; Al- Herz, Waleed; Cancrin, Caterina; Cifald, Cristina; Baris, Safa; Sharapova, Svetlana; Schuetz, Catharina; Gennery, Andrew; Freeman, Alexandra; Somech, Raz; Choo, Sharon; Giliani, Silvia; Güngör, Tayfun; Drozdov, Daniel; Meyt, Isabelle; Moshous, Despina; Neven, Benedicte; Abraham, Roshini; El- Marsafy, Aisha; Kanariou, Maria; King, Alejandra; Licciardi, Francesco; Cruz, Mario; Palma, Paolo; Poli Harlowe, María Cecilia; Adelo, Mehdi; Algeri, Mattia; Alroqi, Fayhan; Bastard, Paul; Bergerson, Jenna; Booth, Claire; Brett, Ana; Burns, Siobhan; Butt, Manish; Padem, Nurcicek; de la Morena, M. Teresa
    Competing interests: M.J.B. is a speaker for Grifols; consults for Pharming, Horizon/Amgen, and Grifols; receives sponsored research funding from the NIH, the Bill and Melinda Gates Foundation, and Pharming; and serves on the scientific advisory board for ADMA Biologics. H.C.S. has stock holdings in Amgen and Eli Lily. R.S.A. receives royalties from Elsevier for book publications, serves as deputy editor for the Journal of Immunology, is Committee Chair of Newborn Screening for SCID for the Clinical and Laboratory Standards Institute, and is a member of the Immunology Clinical Domain Working Group for ClinGen. B.J.D.S. is an ad hoc consultant for Sobi and a member of the Data Safety Monitoring Board for Orchard Therapeutics. I.M. is a senior Clinical Researcher at the FWO Flanders. R.L.F. has consulted for Takeda, Griffons, Horizon, and Pharming. B.W. serves as consultant for the Immunology Speakers Bureau, Takeda Pharmaceutocals. S. Prockop receives support for the conduct of clinical trials through Boston Children’s Hospital from AlloVir, Atara, and Jasper. She is an inventor of intellectual property related to development of third-party virus-specific T cells program with all rights assigned to Memorial Sloan Kettering Cancer Center; receives honoraria from Pierre Fabre, Regeneron; serves on the data safety monitoring board at Stanford University and New York Blood Center; and is consulting for Atara, Ensoma, Pierre Fabre, HEOR and VOR. J.S.T. serves on the scientific advisory board of CytoReason Inc. and Immunoscape Inc. and as the co–chief science officer (unpaid) of the Human Immunome Project (nonprofit). All other authors declare that they have no competing interests.

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