Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals
| Autor: | Emily K, Sims, Brian N, Bundy, Kenneth, Stier, Elisavet, Serti, Noha, Lim, S Alice, Long, Susan M, Geyer, Antoinette, Moran, Carla J, Greenbaum, Carmella, Evans-Molina, Kevan C, Herold, Anette-Gabriele, Ziegler |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment T cell 030209 endocrinology & metabolism CD8-Positive T-Lymphocytes Antibodies Monoclonal Humanized Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Humans Insulin Proinsulin Type 1 diabetes C-Peptide Teplizumab C-peptide business.industry Area under the curve General Medicine medicine.disease Diabetes Mellitus Type 1 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry business CD8 medicine.drug |
| Zdroj: | Sci Transl Med |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.abc8980 |
| Popis: | We analyzed the effects of a single 14-day course of teplizumab treatment on metabolic function and immune cells among participants in a previously reported randomized controlled trial of nondiabetic relatives at high risk for type 1 diabetes (T1D). In an extended follow-up (923-day median) of a previous report of teplizumab treatment, we found that the median times to diagnosis were 59.6 and 27.1 months for teplizumab- and placebo-treated participants, respectively (HR = 0.457, P = 0.01). Fifty percent of teplizumab-treated but only 22% of the placebo-treated remained diabetes-free. Glucose tolerance, C-peptide area under the curve (AUC), and insulin secretory rates were calculated, and relationships to T cell subsets and function were analyzed. Teplizumab treatment improved beta cell function, reflected by average on-study C-peptide AUC (1.94 versus 1.72 pmol/ml; P = 0.006). Drug treatment reversed a decline in insulin secretion before enrollment, followed by stabilization of the declining C-peptide AUC seen with placebo treatment. Proinsulin:C-peptide ratios after drug treatment were similar between the treatment groups. The changes in C-peptide with teplizumab treatment were associated with increases in partially exhausted memory KLRG1+TIGIT+CD8+ T cells (r = 0.44, P = 0.014) that showed reduced secretion of IFNγ and TNFα. A single course of teplizumab had lasting effects on delay of T1D diagnosis and improved beta cell function in high-risk individuals. Changes in CD8+ T cell subsets indicated that partially exhausted effector cells were associated with clinical response. Thus, this trial showed improvement in metabolic responses and delay of diabetes with immune therapy. |
| Databáze: | OpenAIRE |
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