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1.
Egyptian Journal of Medical Microbiology. 2007; 16 (2): 365-376
in English | IMEMR | ID: emr-197660

ABSTRACT

Background: Although dementia of the Alzheimer's type [DAT] is a major threat for the rapidly aging world population and is the leading cause of dementia and a major cause of death in developed countries, no biological marker is available for definitive diagnosis. An increase in immune cells expressing CD45RO was found in brain tissue of patients with DAT. In addition, a decline in peripheral T-cells expressing CD45RA and a rise in CD45RO/CD45RA T cell ratio with increased susceptibility to infection have been encountered in advanced age. This increased susceptibility is even more in patients with DAT


Objectives: To evaluate the expression of CD45 isoforms CD45RA [marker of naïve lymphocytes] and CD45RO [marker of memory lymphocytes] on peripheral T-lymphocytes of patients with DAT at different phases of the disease and investigate the potential usefulness of a testing strategy using CD45 isoforms alteration on T-cells in the diagnosis and prognosis of DAT and in discriminating the disease from aging process


Patients and Methods: Flowcytometric analysis was used to measure the percentage of peripheral blood T-lymphocytes expressing either CD45RA or CD45RO in 25 patients with DAT as well as 25 old subjects and 23 healthy young individuals as controls


Results: The percentage of CD45RA+ T-cells in DAT patients was significantly decreased as compared to that of young controls. It was also decreased in DAT patients with respect to elderly controls and in elderly controls in relation to young controls, however, the difference was not statistically significant. The percentage of CD45RA+ T-cells was also significantly decreased in DAT of early age of onset in comparison to that in late age of onset. As regards the percentage of CD45RO+ T-cells, no significant difference was detected between any of the studied groups. Considering the CD45RO/CD45RA T-cell ratio, it has been significantly increased in DAT patients and elderly subjects in relation to young controls while it was slightly increased in DAT patients compared to elderly controls. According to disease severity, no significant statistical difference was detected between mild, moderate and severe cases as regards CD45RA and CD45RO expression on T-cells and CD45RO/CD45RA T-cell ratio


Conclusion: The decrease in the peripheral T-lymphocytes expressing CD45RA and the increase in the CD45RO/CD45RA T-cell ratio is most probably an aging process, thus it can not be used as a diagnostic or prognostic marker of DAT and the use of additional markers are still needed to be investigated

2.
Egyptian Journal of Medical Microbiology. 2007; 16 (3): 533-541
in English | IMEMR | ID: emr-197680

ABSTRACT

Background: Systemic sclerosis [SSc] is a distinctive idiopathic autoimmune connective tissue disease characterized by widespread vasculopathy and excessive fibrosis in the skin and internal organs, including the heart, lungs, and gastrointestinal tract. The etiology of SSc is unknown. Viruses, including human parvovirus B19 [B19] and human cytomegalovirus, have been implicated as potential causative agents. The demonstration of B19 in a high percentage of bone marrow biopsies from SSc patients, in the absence of demonstrable viremia, suggests a possible role for B19 infection in the evolution of the disease. Circulating tumor necrosis factor-alpha [TNF-alpha] is detectable during acute and convalescent parvovirus B19 infection


Objective: This study aimed to determine whether B19 DNA can be detected in the skin lesions of SSc, in an attempt to investigate a possible role of this virus in the pathogenesis of this disease, and whether this role, if present, is mediated via TNF-alpha


Patients and Methods: This study included 26 cases of SSc and 10 age and sex matched apparently healthy subjects as the control group. Skin biopsies were obtained from the lesional skin of SSc patients and from the healthy controls. Purified DNA and RNA were extracted from the skin samples for detection of B19 DNA using nested PCR and TNF-alpha mRNA gene expression by reverse transcriptase [RT]-PCR


Results: B19 DNA was detected in the skin biopsy samples of 15 patients [57.7%] with SSc. On the other hand, it was absent in all the control biopsies. A highly statistically significant [p<0.001] increase in TNF-alpha expression was detected in the skin of SSc patients as compared to the skin of control subjects. TNF-alpha was also significantly [p<0.05] expressed in the B19 negative skin samples as compared to B19 positive skin of SSc patients


Conclusion: The findings of the current study support the presence of a role for B19 in the pathogenesis of skin lesion in SSc

3.
Egyptian Journal of Medical Microbiology. 2007; 16 (3): 543-551
in English | IMEMR | ID: emr-197681

ABSTRACT

Background: Systemic Lupus Erythematosus [SLE] remains a potentially disabling, life-threatening and overall challenging disease. The role of T cell derived cytokine production in SLE is poorly understood. It was hypothesized that interferon-gamma [IFN-gamma] and interleukin-10 [IL-10] are important cytokines in the pathogenesis of SLE. Understanding their possible role in the pathogenesis might lead to the development of new, more targeted drugs to manage this intractable disease


Objectives: To study IFN-gamma and IL-10 mRNA expression in peripheral blood mononuclear cells [PBMCs] in patients with SLE, correlating them with the disease activity score as measured by Systemic Lupus Activity Measures [SLAM] score; in an attempt to throw light on their possible role in the pathogenesis of the disease


Subjects: Forty selected patients with SLE [15 with active disease as group I, and 25 in remission as group II] and 15 healthy controls with matched ages and sex were studied


Methods: Using reverse transcriptase-polymerase chain reaction [RT-PCR], IFN-gamma and IL-10 mRNA expression in PBMCs was measured in both patients and controls


Results: This study showed a significant [p<0.05] decrease in haemoglobin and lymphocyte percents in patients than in controls and a significant [p<0.05] increase in expression of both IFN-gamma and IL-10 mRNA in PBMCs of patients than controls. The IFN-gamma expression was higher in group I of patients than those in group II, however, this difference did not attain statistical significance [p>0.05]. There was also no statistically significant [p>0.05] difference between both groups of patients as regards IL-10 expression. A significant positive correlation was detected between IFN-gamma expression and SLAM score [r=0.36, p=0.02], also between IL-10 expression and duration of illness [r=0.175, p=0.018], and between IFN-gamma expression and IL-10 expression [r=0.85, p<0.001] but both IFN-gamma and IL-10 expression were negatively [insignificant] correlated with cortisone intake [r=0.22, p=0.06 and r=0.12, p=0.5, respectively]


Conclusion: Results of this work support the hypothesis that IFN-gamma and IL-10 play a key role in the immunopathogenesis of SLE and suggests that IFN-gamma might be considered as an important independent marker of disease activity

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