Progression of type 1 diabetes is associated with high levels of soluble PD-1 in islet autoantibody-positive children.

Autor: Bruzzaniti S; Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Naples, Italy., Piemonte E; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Naples, Italy., Bruzzese D; Dipartimento di Sanità Pubblica, Università degli Studi di Napoli 'Federico II', Naples, Italy., Lepore MT; Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Naples, Italy., Strollo R; Dipartimento di Scienze Umane e Promozione della Qualità della Vita, Università Telematica San Raffaele Roma, Rome, Italy., Izzo L; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Naples, Italy., Di Candia F; Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli 'Federico II', Naples, Italy., Franzese A; Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli 'Federico II', Naples, Italy., Bifulco M; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Naples, Italy., Mozzillo E; Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli 'Federico II', Naples, Italy., Ludvigsson J; Crown Princess Victoria's Children's Hospital and Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. Johnny.Ludvigsson@liu.se., Matarese G; Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Naples, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Naples, Italy., Galgani M; Laboratorio di Immunologia, Istituto per l'Endocrinologia e l'Oncologia Sperimentale 'G. Salvatore', Consiglio Nazionale delle Ricerche, Naples, Italy. mario.galgani@unina.it.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli 'Federico II', Naples, Italy. mario.galgani@unina.it.
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2024 Apr; Vol. 67 (4), pp. 714-723. Date of Electronic Publication: 2024 Jan 12.
DOI: 10.1007/s00125-023-06075-3
Abstrakt: Aims/hypothesis: Type 1 diabetes is an autoimmune disorder that is characterised by destruction of pancreatic beta cells by autoreactive T lymphocytes. Although islet autoantibodies (AAb) are an indicator of disease progression, specific immune biomarkers that can be used as target molecules to halt development of type 1 diabetes have not been discovered. Soluble immune checkpoint molecules (sICM) play a pivotal role in counteracting excessive lymphocyte responses, but their role in type 1 diabetes is unexplored. In this longitudinal study, we measured sICM levels in AAb-positive (AAb + ) children to identify molecules related to type 1 diabetes progression.
Methods: We measured the levels of 14 sICM in the sera of AAb + children (n=57) compared to those with recent-onset type 1 diabetes (n=79) and healthy children (n=44), obtained from two cohorts. AAb + children were followed up and divided based on their progression to type 1 diabetes (AAb P ) or not (AAb NP ) (if they lost islet autoimmunity and did not develop disease in subsequent years). sICM were also measured in the sample taken at the visit closest to disease onset in AAb P children.
Results: We found that AAb + children had a distinct sICM profile compared with healthy children and those with recent-onset type 1 diabetes. In addition, AAb + children who progressed to type 1 diabetes (AAb P ) had higher sICM concentrations than non-progressors (AAb NP ). Further, sICM levels decreased in AAb P children close to disease onset. Application of Cox regression models highlighted that high concentrations of soluble programmed cell death protein 1 (sPD-1) are associated with type 1 diabetes progression (HR 1.71; 95% CI 1.16, 2.51; p=0.007).
Conclusions/interpretation: This study reveals an sICM profile that is dysregulated during the preclinical stage of type 1 diabetes, and identifies sPD-1 as a pathophysiologically-relevant molecule that is associated with disease progression, offering a potential target for early interventions in autoimmune diabetes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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