Guidelines for standardizing T cell cytometry assays to link biomarkers, mechanisms, and disease outcomes in type 1 diabetes

Author(s):  
Jennie H. M. Yang ◽  
Kirsten A. Ward‐Hartstonge ◽  
Daniel J. Perry ◽  
J. Lori Blanchfield ◽  
Amanda L. Posgai ◽  
...  
2021 ◽  
Vol 08 (01) ◽  
pp. 011-018
Author(s):  
Khalid E. Khalid Kheiralla

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.


2021 ◽  
Vol 9 (6) ◽  
pp. 1177
Author(s):  
Abdulaziz Alhazmi ◽  
Magloire Pandoua Nekoua ◽  
Hélène Michaux ◽  
Famara Sane ◽  
Aymen Halouani ◽  
...  

The thymus gland is a primary lymphoid organ for T-cell development. Various viral infections can result in disturbance of thymic functions. Medullary thymic epithelial cells (mTECs) are important for the negative selection of self-reactive T-cells to ensure central tolerance. Insulin-like growth factor 2 (IGF2) is the dominant self-peptide of the insulin family expressed in mTECs and plays a crucial role in the intra-thymic programing of central tolerance to insulin-secreting islet β-cells. Coxsackievirus B4 (CVB4) can infect and persist in the thymus of humans and mice, thus hampering the T-cell maturation and differentiation process. The modulation of IGF2 expression and protein synthesis during a CVB4 infection has been observed in vitro and in vivo in mouse models. The effect of CVB4 infections on human and mouse fetal thymus has been studied in vitro. Moreover, following the inoculation of CVB4 in pregnant mice, the thymic function in the fetus and offspring was disturbed. A defect in the intra-thymic expression of self-peptides by mTECs may be triggered by CVB4. The effects of viral infections, especially CVB4 infection, on thymic cells and functions and their possible role in the pathogenesis of type 1 diabetes (T1D) are presented.


2021 ◽  
Vol 10 (7) ◽  
Author(s):  
Johnna D Wesley ◽  
Susanne Pfeiffer ◽  
Darius Schneider ◽  
David Friedrich ◽  
Nikole Perdue ◽  
...  

Author(s):  
Josefine Wadenpohl ◽  
Julia Seyfarth ◽  
Paul Hehenkamp ◽  
Maximilian Hoffmann ◽  
Sebastian Kummer ◽  
...  

Diabetes ◽  
2008 ◽  
Vol 57 (5) ◽  
pp. 1312-1320 ◽  
Author(s):  
E. Martinuzzi ◽  
G. Novelli ◽  
M. Scotto ◽  
P. Blancou ◽  
J.-M. Bach ◽  
...  

2010 ◽  
Vol 135 ◽  
pp. S19
Author(s):  
Brian Hondowicz ◽  
Katharine Schwedhelm ◽  
Arnold Kas ◽  
Michael Tasch ◽  
Nirasha Ramchurren ◽  
...  

2010 ◽  
Vol 34 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Christian Pfleger ◽  
Guido Meierhoff ◽  
Hubert Kolb ◽  
Nanette C. Schloot

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