Natural history of type 1 diabetes on an immunodysregulatory background with genetic alteration in B-cell activating factor receptor: A case report.

Autor:	Di Lorenzo B; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Pacillo L; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Milardi G; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Jofra T; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Di Cesare S; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy., Gerosa J; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Marzinotto I; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Zapparoli E; Center for Omics Sciences, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milano, Italy., Rivalta B; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Cifaldi C; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Barzaghi F; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.; Pediatric Immunohematology and Bone Marrow Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Giancotta C; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Zangari P; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Rapini N; Unit of Endocrinology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Deodati A; Unit of Endocrinology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Amodio G; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Passerini L; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Carrera P; Unit of Genomics for Human Disease Diagnosis and Laboratory of Clinical Molecular Biology, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Gregori S; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy., Palma P; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Finocchi A; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Lampasona V; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Cicalese MP; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.; Pediatric Immunohematology and Bone Marrow Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.; Faculty of Medicine, University Vita-Salute San Raffaele, Milan, Italy., Schiaffini R; Unit of Endocrinology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Di Matteo G; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy., Merelli I; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.; Department of Bioinformatics, Institute for Biomedical Technologies National Research Council, Segrate, Italy., Barcella M; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.; Department of Bioinformatics, Institute for Biomedical Technologies National Research Council, Segrate, Italy., Aiuti A; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.; Pediatric Immunohematology and Bone Marrow Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.; Faculty of Medicine, University Vita-Salute San Raffaele, Milan, Italy., Piemonti L; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy., Cancrini C; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.; Academic Department of Pediatrics (DPUO), Research Unit of Clinical Immunology and Vaccinology, Bambino Gesú Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy., Fousteri G; Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Aug 26; Vol. 13, pp. 952715. Date of Electronic Publication: 2022 Aug 26 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.952715
Abstrakt:	The immunological events leading to type 1 diabetes (T1D) are complex and heterogeneous, underscoring the necessity to study rare cases to improve our understanding. Here, we report the case of a 16-year-old patient who showed glycosuria during a regular checkup. Upon further evaluation, stage 2 T1D, autoimmune thrombocytopenic purpura (AITP), and common variable immunodeficiency (CVID) were diagnosed. The patient underwent low carb diet, losing > 8 kg, and was placed on Ig replacement therapy. Anti-CD20 monoclonal antibody (Rituximab, RTX) was administered 2 years after diagnosis to treat peripheral polyneuropathy, whereas an atypical mycobacteriosis manifested 4 years after diagnosis and was managed with prolonged antibiotic treatment. In the fifth year of monitoring, the patient progressed to insulin dependency despite ZnT8A autoantibody resolution and IA-2A and GADA autoantibody decline. The patient had low T1D genetic risk score (GRS = 0.22817) and absence of human leukocyte antigen (HLA) DR3/DR4-DQ8. Genetic analysis identified the monoallelic mutation H159Y in TNFRSF13C , a gene encoding B-cell activating factor receptor (BAFFR). Significant reduced blood B-cell numbers and BAFFR levels were observed in line with a dysregulation in BAFF-BAFFR signaling. The elevated frequency of PD-1 + dysfunctional Tfh cells composed predominantly by Th1 phenotype was observed at disease onset and during follow-up. This case report describes a patient progressing to T1D on a BAFFR-mediated immunodysregulatory background, suggesting a role of BAFF-BAFFR signaling in islet-specific tolerance and T1D progression. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Di Lorenzo, Pacillo, Milardi, Jofra, Di Cesare, Gerosa, Marzinotto, Zapparoli, Rivalta, Cifaldi, Barzaghi, Giancotta, Zangari, Rapini, Deodati, Amodio, Passerini, Carrera, Gregori, Palma, Finocchi, Lampasona, Cicalese, Schiaffini, Di Matteo, Merelli, Barcella, Aiuti, Piemonti, Cancrini and Fousteri.)
Databáze:	MEDLINE
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