Cytokine profile and insulin antibody IgG subclasses in patients with recent onset Type 1 diabetes treated with oral insulin |
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Authors: | L.?Monetini,M.?G.?Cavallo,E.?Sarugeri,F.?Sentinelli,L.?Stefanini,E.?Bosi,R.?Thorpe,P.?Pozzilli author-information" > author-information__contact u-icon-before" > mailto:p.pozzilli@unicampus.it" title=" p.pozzilli@unicampus.it" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author,the Immunotherapy Diabetes group |
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Affiliation: | (1) Department of Endocrinology and Diabetes, University Campus Bio-Medico, Via Longoni 83, 00155 Rome, Italy;(2) Department of Clinical Medicine and Therapeutics, University La Sapienza , Rome, Italy;(3) Internal Medicine, Diabetes and Endocrinology Unit, Vita-Salute San Raffaele University Hospital, Milan, Italy;(4) Department of Clinical Sciences, Endocrinology, University La Sapienza , Rome, Italy;(5) Division of Immunobiology, National Institute for Biological Standards and Control, South Mimms, UK;(6) Department of Diabetes, Institute of Cell and Molecular Science, Queen Mary College, St. Bartholomew s Hospital, London, UK |
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Abstract: | Aims/hypothesis Tolerance to orally administered antigens may be generated through the induction of T helper cell type 2 and 3 (Th2/Th3) regulatory cells. We previously reported that treatment of recent onset Type 1 diabetes with oral insulin had no effect on residual beta cell function. The aim of this study was to evaluate whether this treatment produces a deviation in the immune response, with polarisation of the cytokine pattern and the induction of a Th2-like antibody response.Methods Mononuclear cells were collected from a total of 20 patients with Type 1 diabetes before and after 12 months of treatment with oral insulin (n=11) or placebo (n=9). Following stimulation of the cells with insulin or phytohaemagglutinin, levels of Th2 and Th3 cytokines (including TGF- , IFN- , IL-4 and IL-5) in the culture supernatants were assessed by ELISA. In addition, levels of total and specific insulin antibody IgG subclasses were measured by radioimmunoassay in serum samples drawn from 33 patients with Type 1 diabetes before and after 3, 6 and 12 months of therapy with oral insulin (n=18) or placebo (n=15).Results After 12 months of treatment, the release of TGF- was significantly higher in patients who received oral insulin compared with those who received placebo (p=0.025 and p=0.006 for lymphocytes challenged with insulin and phytohaemagglutinin respectively). The two groups had similar levels of IL-4 and IL-5 both at baseline and after 12 months of treatment. The release of IFN- was markedly reduced in patients treated with oral insulin compared with those who received placebo at the 12-month follow-up. Circulating levels of IgG1 and IgG3 subclasses directed against insulin were significantly lower in the oral insulin group than in the placebo group after 12 months of treatment (p=0.05 for IgG1 and p=0.014 for IgG3).Conclusions/interpretation The increased TGF- release observed in patients treated with oral insulin suggests that a regulatory response can be induced in vivo by this treatment. The lower levels of insulin antibody IgG1 and IgG3 subclasses present in patients exposed to oral insulin are consistent with a Th2 deviation of the immune response. The failure of oral insulin treatment to provide any measurable clinical benefit may be due to the timing of treatment initiation. |
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Keywords: | Cytokines IgG insulin antibodies Oral insulin Type 1 diabetes |
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