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EG |
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| Egypt J Pediatr Allergy Immunol |
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2008 |
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6 |
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02 |
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57-67 |
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ESP - 74 |
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| Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus |
| Eman M. Sherif |
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Amira A.M. Adly |
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Hala G. Mohamed |
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Ali Ahmed |
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| Background: Beta cell apoptosis has been associated with insulin dependent
diabetes mellitus (IDDM) onset in newly diagnosed diabetic patients. There
is an emerging evidence that T cell-induced apoptosis is a dominant effector
mechanism in diabetes mellitus type 1 (DM1). Pancreatic ?-cells derived
from newly diagnosed type 1 diabetics were found to have increased cell
surface expression of Fas (CD95) compared to ?-cells from healthy subjects.
Objective: The study investigates the spontaneous lymphocyte apoptosis via
CD95 molecule expression to demonstrate activation induced cell death in
children with high risk of DM1 and in type 1 diabetics under insulin therapy.
Methods: This study comprised 90 children and adolescents, divided into 3
groups. G(1) comprised 40 type-1 diabetics, their ages ranging from 8.0 to
17.0 years and disease duration between 2.0 and 12.0 years. G(2)
(prediabetics) included 30 euglycaemic subjects who were first degree
relatives of type 1 diabetics, with normal fasting blood glucose and positive
first phase insulin release (FPIR) and/or positive islet cell (ICA) or glutamic
acid decarboxylase (GAD) antibodies. G(3) comprised 20 healthy, age and
sex matched subjects with no clinical or laboratory signs or family history of
type-1DM. Patients were subjected to clinical evaluation with special
emphasis on signs suggestive of microvascular complications. The study
measurements included random blood sugar (RBS), glycosylated
hemoglobin (HbA1c), urinary microalbumin assay and flow cytometric
assessment of apoptosis by measuring CD95 percentage expression on CD3
lymphocytes.
Results: The percentage of CD95 positive T-lymphocytes was significantly
higher in prediabetics than in type-1 diabetics and controls (57.687±6.68,
45.01±6.648,16.75±4.98% respectively; p<0.001). CD3 positive
lymphocytes were significantly lower in prediabetics than type-1 diabetics
and controls (52.93±11.64, 66.23±7.04, 63.910±3.4% respectively;
p<0.001). The percentage of CD95 on T-lymphocytes could not be
correlated with age, insulin dose and RBS, but HbA1c was positively
correlated with both CD3 lymphocytes and CD95% expression. Complicated
type-1 diabetics showed higher CD95% expression compared to noncomplicated
patients.
Conclusion: Peripheral blood lymphocytes with CD95 antigen expression
are increased in prediabetics. As CD95 is an important receptor for
activation-induced cell death, CD95 mediated apoptosis could play a
potential role in the pathogenesis of DM1. |
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