The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus

Aim. To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease. Materials and methods. 70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57...

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Autores principales:	Tatiana Vladimirovna Saprina, F E Lazarenko, T S Prokhorenko, N V Ryazantseva, Irina Nikolaevna Vorozhtsova
Formato:	article
Lenguaje:	EN RU
Publicado:	Endocrinology Research Centre 2011
Materias:	latent autoimmune diabetes mellitus in adults type 1 diabetes cytokines immunopathogenesis Nutritional diseases. Deficiency diseases RC620-627
Acceso en línea:	https://doaj.org/article/0183da0f38ef414a8c51d8b5a5d808bf
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id	oai:doaj.org-article:0183da0f38ef414a8c51d8b5a5d808bf
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN RU
topic	latent autoimmune diabetes mellitus in adults type 1 diabetes cytokines immunopathogenesis Nutritional diseases. Deficiency diseases RC620-627
spellingShingle	latent autoimmune diabetes mellitus in adults type 1 diabetes cytokines immunopathogenesis Nutritional diseases. Deficiency diseases RC620-627 Tatiana Vladimirovna Saprina F E Lazarenko T S Prokhorenko N V Ryazantseva Irina Nikolaevna Vorozhtsova The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus
description	Aim. To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease. Materials and methods. 70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57 DM2 patients (34.6?7.2 and 43.6?7.6 yr respectively). 27 DM2 patients (41.2?1.6 yr) presumably had LADA (P. Zimmet's criteria).Serum anti-GAD65, ICA, and IAA antibodies along with C-peptide were measured in fasting sera and 120 min after GTT by solid phase immunoenzymeassays following manufacturer's instructions with the use of a photometer for Multiscan EX microplates (ThermoLabSystems, Finland) at405 nm (for GAG and ICA) and 450 nm (for IAA and C-peptide). GAD, IAA, and C-peptides levels were calculated automatically from calibrationcurves. Mononuclear leukocytes were isolated by centrifugation in the ficoll-verographin density gradient. The cells thus obtained were resuspendedin the complete nutritient medium reducing their concentration to 2.0x10^6/ml. Phytohemagglutinin (Difco, Germany) was added (10 mcg/1 ml) tothe samples to stimulate mononuclear leukocytes; cell suspensions were further incubated for 24 hr. Initial and PGA-induced levels of IL-2, 4, 10 insupernatants of cell cultures were measured by solid phase immunoassay at 450 nm. Results. At least one type of autoantibodies (GAD, ICA or IAA) was identified in 24.3% of all DM patients (17/70) and in 18% of the DM2 patients(10/57). The level of anti-GAD and ICA ABs and percentage of AB-positive patients were higher in the LADA group while that of anti-IAA ABs amongDM1 patients without LADA. Two AB types at a time were found in 17% (4/23) of the patients with autoimmune DM in the absence of significantdifference between LADA and DM1. Patients with LADA had a significantly lower basal C-peptide level than DM2 patients. The was a tendencytoward lower level of stimulated C-peptide secretion in LADA patients compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response. Conclusion. The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.
format	article
author	Tatiana Vladimirovna Saprina F E Lazarenko T S Prokhorenko N V Ryazantseva Irina Nikolaevna Vorozhtsova
author_facet	Tatiana Vladimirovna Saprina F E Lazarenko T S Prokhorenko N V Ryazantseva Irina Nikolaevna Vorozhtsova
author_sort	Tatiana Vladimirovna Saprina
title	The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus
title_short	The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus
title_full	The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus
title_fullStr	The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus
title_full_unstemmed	The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus
title_sort	role of th1/th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus
publisher	Endocrinology Research Centre
publishDate	2011
url	https://doaj.org/article/0183da0f38ef414a8c51d8b5a5d808bf
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spelling	oai:doaj.org-article:0183da0f38ef414a8c51d8b5a5d808bf2021-11-14T09:00:16ZThe role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus2072-03512072-037810.14341/2072-0351-5628https://doaj.org/article/0183da0f38ef414a8c51d8b5a5d808bf2011-06-01T00:00:00Zhttps://www.dia-endojournals.ru/jour/article/view/5628https://doaj.org/toc/2072-0351https://doaj.org/toc/2072-0378Aim. To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease. Materials and methods. 70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57 DM2 patients (34.6?7.2 and 43.6?7.6 yr respectively). 27 DM2 patients (41.2?1.6 yr) presumably had LADA (P. Zimmet's criteria).Serum anti-GAD65, ICA, and IAA antibodies along with C-peptide were measured in fasting sera and 120 min after GTT by solid phase immunoenzymeassays following manufacturer's instructions with the use of a photometer for Multiscan EX microplates (ThermoLabSystems, Finland) at405 nm (for GAG and ICA) and 450 nm (for IAA and C-peptide). GAD, IAA, and C-peptides levels were calculated automatically from calibrationcurves. Mononuclear leukocytes were isolated by centrifugation in the ficoll-verographin density gradient. The cells thus obtained were resuspendedin the complete nutritient medium reducing their concentration to 2.0x10^6/ml. Phytohemagglutinin (Difco, Germany) was added (10 mcg/1 ml) tothe samples to stimulate mononuclear leukocytes; cell suspensions were further incubated for 24 hr. Initial and PGA-induced levels of IL-2, 4, 10 insupernatants of cell cultures were measured by solid phase immunoassay at 450 nm. Results. At least one type of autoantibodies (GAD, ICA or IAA) was identified in 24.3% of all DM patients (17/70) and in 18% of the DM2 patients(10/57). The level of anti-GAD and ICA ABs and percentage of AB-positive patients were higher in the LADA group while that of anti-IAA ABs amongDM1 patients without LADA. Two AB types at a time were found in 17% (4/23) of the patients with autoimmune DM in the absence of significantdifference between LADA and DM1. Patients with LADA had a significantly lower basal C-peptide level than DM2 patients. The was a tendencytoward lower level of stimulated C-peptide secretion in LADA patients compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response. Conclusion. The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.Tatiana Vladimirovna SaprinaF E LazarenkoT S ProkhorenkoN V RyazantsevaIrina Nikolaevna VorozhtsovaEndocrinology Research Centrearticlelatent autoimmune diabetesmellitus in adultstype 1 diabetescytokinesimmunopathogenesisNutritional diseases. Deficiency diseasesRC620-627ENRUСахарный диабет, Vol 14, Iss 2, Pp 12-17 (2011)

The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus

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