Hypoglycaemia induces recruitment of non-classical monocytes and cytotoxic lymphocyte subsets in type 1 diabetes

Abstract Background Type 1 diabetes mellitus (T1DM) is an organ-specific T cell-mediated autoimmune disease, characterized by destruction of pancreatic islets. Cytotoxic lymphocyte antigen-4 (CTLA-4) is a negative regulator of T cell proliferation, thus conferring susceptibility to autoimmunity. Aims This study aimed to investigate the association of CTLA-4 +49A/G (rs231775) polymorphism with a risk of T1DM in Sudanese children. Methods This a case–control study included 100 children with T1DM, referred to the pediatric clinic at referral pediatric teaching hospital in Gezira State-Sudan. Hundred unrelated healthy controls were recruited from departments in the same hospital. Genomic deoxyribonucleic acid (DNA) was extracted from Ethylenediaminetetraacetic Acid (EDTA)-preserved blood using QIAamp DNA Blood Mini Kit (QIAamp Blood) (QIAGEN; Valencia, CA). The polymerase chain reaction PCR restriction fragment length polymorphism (PCR-RFLP) and sequencing were applied for the CTLA-4 (+49A/G) genotyping. The changes accompanied the polymorphism were evaluated using relevant bioinformatics tools. Results The genotype and allele frequencies of the CTLA-4 (+49A/G) polymorphism were significantly different between the patients and controls (p = 0.00013 and 0.0002, respectively). In particular, the frequency of the G allele, GG homozygous genotype, and AG heterozygous genotype were significantly increased in patients than in controls ([28% versus 7%, odds ratio (OR) = 5.16, 95% confidence interval [CI] = 2.77–9.65, p = 0.00] [12% versus 2%, OR = 6.68, CI = 1.46–30.69, p = 0.01] [32% versus 10%, OR = 4.24, CI = 1.95–9.21, p = 0.00], respectively). The presence of the G allele (homozygous) showed an influence on the signal peptide polarity, hydrophobicity, and α-helix propensity of the CTLA-protein. Conclusion The results further support the association of CTLA-4 (+49A/G) polymorphism and the risk of T1DM in our study population.

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Changes in Lymphocyte Subsets in Children with Newly Diagnosed Type 1 Diabetes Mellitus

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.2003.16.2.185 ◽

2003 ◽

Vol 16 (2) ◽

Cited By ~ 2

Author(s):

Κ. Kądziela ◽

Η. Kowalska ◽

Β. Rymkiewicz-Kluczynska ◽

Μ. Kowalska ◽

G. Miszkurka ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Lymphocyte Subsets ◽

Newly Diagnosed

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Effect of Photopheresis on Lymphocyte Population in Children with Newly Diagnosed Type 1 Diabetes

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.5.856-861.2004 ◽

2004 ◽

Vol 11 (5) ◽

pp. 856-861 ◽

Cited By ~ 7

Author(s):

J. Ernerudh ◽

J. Ludvigsson ◽

G. Berlin ◽

U. Samuelsson

Keyword(s):

Type 1 Diabetes ◽

Placebo Group ◽

Lymphocyte Subsets ◽

Randomized Study ◽

Disease Process ◽

Treated Group ◽

Newly Diagnosed ◽

Recent Infection ◽

Double Blind

ABSTRACT In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4+CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29+) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.

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Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults

Diabetes Care ◽

10.2337/dc15-1765 ◽

2015 ◽

Vol 39 (3) ◽

pp. 434-440 ◽

Cited By ~ 43

Author(s):

Chao Deng ◽

Yufei Xiang ◽

Tingting Tan ◽

Zhihui Ren ◽

Chuqing Cao ◽

...

Keyword(s):

Type 1 Diabetes ◽

B Lymphocyte ◽

Lymphocyte Subsets ◽

Autoimmune Diabetes ◽

Latent Autoimmune Diabetes

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Peripheral Blood Cytotoxic Lymphocyte Gene Transcript Levels Differ in Patients with Long-Term Type 1 Diabetes Compared to Normal Controls

Cell Transplantation ◽

10.3727/000000005783982972 ◽

2005 ◽

Vol 14 (6) ◽

pp. 403-409 ◽

Cited By ~ 7

Author(s):

Dongmei Han ◽

Jenifer Leith ◽

Rodolfo Alejandro ◽

Wade Bolton ◽

Camillo Ricordi ◽

...

Keyword(s):

Type 1 Diabetes ◽

Peripheral Blood ◽

Gene Transcript ◽

Mrna Levels ◽

Cytotoxic Lymphocyte ◽

Transcript Levels ◽

Term Type ◽

Normal Controls

The purpose of this study was to compare mRNA levels of the cytotoxic lymphocyte (CL) gene products: granzyme B (GB), perforin (P), and fas ligand (FasL) in patients with long-term type 1 diabetes and healthy controls. The objective was to utilize this information to follow patients as they undergo islet cell transplantation at our center and to determine if changes in CL gene transcript levels correlate with graft status. We have measured mRNA levels for CL genes in peripheral blood samples from 65 long-term (>5 years) type 1 diabetes patients and 29 healthy controls. Total RNA was extracted from EDTA anticoagulated peripheral blood samples and reverse transcribed into first-strand cDNA using SuperScript II reverse Transcriptase. Quantitative, real-time PCR was utilized to determine CL gene transcript levels. mRNA levels of P and FasL genes were found to be significantly lower for patients with type 1 diabetes compared to normal controls (p < 0.05). However, there was no significant difference for GB mRNA levels between patients and controls (p > 0.05). The decreased expression of P and FasL in patients with long-term type 1 diabetes might contribute to the inability to maintain normal levels of peripheral tolerance, which is essential for protection from autoimmune disease.

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