Naturally Occurring T Regulatory Cells, Interleukins 10 And 12 In The Pathogenesis Of Idiopathic Warm Autoimmune Hemolytic Anemia.

3410 words - 14 pages

ABSTRACT
There is now compelling evidence from animal models autoimmune hemolytic anemia (AIHA) that naturally occurring regulatory T cells (n-Tregs) play an important role in immunologic tolerance and control of immune-mediated pathology. However their study in human AIHA is still ill defined. Aim: To measure the peripheral blood proportions of n-Treg cells and the levels of IL10 and IL12 in basal and mitogen-induced (Lipopolysaccharide, LPS) cultures of PBMCs in patients with idiopathic warm AIHA (wAIHA) in a trial to ravel out some enigmatic aspects in the pathogenesis of this autoimmune disorder. Patients&Methods: This study included 27 patients with idiopathic wAIHA, 9 males and 18 females with male/female ratio 1/1.5. Their ages ranged from 28 to 63 years, mean ± SD (45.3±11 years). 15 age and sex matched healthy individuals were randomly selected as controls, they aged between 23 and 54 years, mean ± SD (44.6±9.2 years). Subjects enrolled in the study were submitted to: full history taking, clinical examination, liver and kidney function tests, complete blood count, flow cytometeric assay of CD4+CD25 highFoxP3+ T cells (n-Tregs), and enzyme linked assay of IL10 and IL12 in the supernatants of basal and LPS stimulated PBMCs cultures. Results : The percentages of circulating CD4+CD25highFoxp3+ T cells (n-Tregs) were found to be significantly lower in patients (4.63 ± 1.0) compared to control (9.76 ± 0.78), p<0.001. PBMCs obtained from AIHA patients showed a highly significant increase of IL10 and IL12 basal levels compared to the controls, p<0.001and p<0.01respectively. After LPS stimulation, the statistical differences between patients and controls in IL10 and IL12 levels were reduced and non significant, p<0.05 and p=0.26 respectively. In patients, there was a statistically negative correlation between n-Tregs percent and reticulocytic count (RC), while there was a statistically positive correlation with haptoglobin (Hp), p<0.05. There was a statistically negative correlation between n-Tregs percent and IL10b&IL10LPS, p<0.05. There was a statistically positive correlation between IL10b&IL10LPS and RC, p<0.001, while there was a statistically negative correlation with Hp, p<0.01 and p<0.05 respectively. Conclusion: Although there may be multiple factors that contribute to the induction of warm AIHA, our data indicate that defective suppressive activity of n-Treg cells and IL10/IL12 imbalance could play an essential role in the onset and/or maintenance of this autoimmune disease. Further investigations in 1ry AIHA syndrome in which autoimmunity is a significant feature, holds the promise of identifying new molecular defects that will further elucidate basic mechanisms of self tolerance and provide new targets for therapy.

Keywords: Autoimmune hemolytic anemia; regulatory T cells; Interleukin10; Interleukin12.


INTRODUCTION
Warm autoimmune hemolytic anemia (wAIHA) accounts for about 50-70% of cases of autoimmune hemolytic...

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