Regulatory T cells number and function in patients with LADA

T Nikonova; E Pekareva; V Gorelysheva; P Apanovich; A Karpuhin; I Dedov

P585

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Endocrine Abstracts (2012) 29 P585

ICEECE2012 Poster Presentations Diabetes (248 abstracts)

Regulatory T cells number and function in patients with LADA

T Nikonova ¹ , E Pekareva ¹ , V Gorelysheva ¹ , P Apanovich ² , A Karpuhin ² & I Dedov ¹

Err

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¹Endocrinology Research Centre, Moscow, Russian Federation; ²Medical Genetics Research Centre, Moscow, Russian Federation.

CD4+CD25+lymphocytes (Tregs) play a crucial role in self-tolerance and autoimmunity. LADA is associated with the loss of immune tolerance to β-cell autoantigens similar to classic type 1 diabetes mellitus. The aim of the study was to evaluate changes in terms of Tregs number and function (FOXP3 expression) in LADA patients.

Material and methods: We examined 74 patients with LADA at different stages of the disease. Fifty-six healthy subjects (control group) were included. The HLA-DR and DQ alleles were detected by using PCR method. CD4+, CD8+, CD25+, CD4+25+, CD95+, CD95L+ cells were analyzed by flow cytometry. FOXP3 expression was determined by real time PCR. All subjects were tested for ICA, GADA, IA-2A, C-peptide, HbA1c.

Results: In recent-onset LADA FOXP3 expression was similar to that in control subjects. However, the percentage of Tregs was significantly higher: 2.1 (0.3; 2.3) vs 0.8 (0.6; 0.8). During the period from 6 to 12 months upon the onset of the disease a reduced FOXP3 expression 0.43 rq (0.11; 0.75) was observed in LADA patients if compared with control subjects with 1.11 rq (0.66; 2.26; P<0.05). There was no significant difference in the percentage of Tregs in this period (P>0.05). FOXP3 expression became normal again after the first and until the 5th year of the disease. Correlation between FOXP3 and Tregs amount was found only in control group. No correlation was established between C-peptide level and autoantibodies titers in LADA patients. In all LADA patients expression of apoptosis markers (CD95 and CD95L) was comparable with the control group (P>0.05). Correlation analysis showed strong positive association between GADA and CD95L expression (r=0.94, P=0.05).

Conclusions: Tregs functional deficiency is delayed in LADA patients. It appears to be compensated by a rise of Tregs number in the first 6 months. This may contribute to slowing β-cells autoimmune destruction.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.