Review Article
Abbas Ghaderi
Volume 8, Issue 3 , September 2011, Pages 127-149
Abstract
Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, ...
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Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, such as Grave’s disease, on which a large body of multicentre data is accumulated. For years the focus of attention was on diversity and polymorphism of major histocompatibility complex in respect to human diseases specially the autoimmune diseases, but in recent years, access to other human gene sequences prompted investigators to focus on genes encoding the immune regulatory proteins such as the co-stimulatory, adhesion molecules, cytokines and chemokines and their receptors. Among them, CTLA4 (CD152) has been in the centre of attention for its pivotal role in autoimmunity and cancer. Although not fully understood, CTLA4 with no doubt plays an important role in the maintenance of the immune response by its expression on activated and regulatory T cells. CTLA4 (Gene ID:1493, MIM number:123890) has many variants and polymorphic forms, some present in regulatory positions, some in 3' UTR and the most important one in the leader sequence (+49 A/G). As a pivotal regulatory element of the immune responses magnitude, CTLA4 could be considered as a two-blade knife, for which only the optimal expression ensures an effective, but at the same time, safe immune response. It can accordingly be speculated that CTLA4 alleles associated with extraordinary expression could make a person more susceptible to tumor growth and/or progression. On the other hand, alleles associated with a compromised CTLA4 expression/function may accelerate the formation and/or manifestation of inflammatory autoimmune disorder. I hypothesized a spectrum of the functional dichotomy of CTLA4 SNPs diverging from autoimmunity to cancer. To examine these hypotheses, results from previously published investigations on CTLA4 polymorphisms together with the work done by our own group are discussed in details. Because the most published data are about the polymorphism at position +49, I concentrated on this position; however the data regarding other SNPs are also included for comparison. To support the significance of CTLA4 gene variation in these two major human diseases evidences from organ transplantation are also included. As will be discussed in the manuscript, our work and reports by others from a normal population perspective support the hypothesis that individuals inheriting a GG genotype at position +49, for which lower CTLA4 expression has been extensively suggested, are more susceptible for developing autoimmune disorders and those with AA genotype, with an existence of a state of self-tolerance, may have a higher chance of developing cancer. CTLA4 SNPs may accordingly be considered as a crucial element, along with other known or yet unknown mechanisms, in keeping the immune balance in predisposed individuals to cancer and autoimmunity. Although an spectrum line can be drawn between autoimmunity and cancer by considering published data regarding CTLA4 +49 polymorphism, the extreme functional dichotomy of this SNP appears to be more complex and difficult to understand, but there is no doubt that the future investigations will resolve most ambiguities.
Original Article
Elfadil Abass; Abdelhafeiz Mahamoud; Durria Mansur; Mehdi Mohebali; Abdollah el Harith
Volume 8, Issue 3 , September 2011, Pages 150-158
Abstract
Background: A β-mercaptoethnol (β-ME)-treated promastigote antigen of L. donovani was successfully employed in direct agglutination test (DAT) for the diagnosis of visceral leishmaniasis (VL). Objective: The β-ME-treated antigen was further incorporated into an enzyme-linked immunosorbent ...
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Background: A β-mercaptoethnol (β-ME)-treated promastigote antigen of L. donovani was successfully employed in direct agglutination test (DAT) for the diagnosis of visceral leishmaniasis (VL). Objective: The β-ME-treated antigen was further incorporated into an enzyme-linked immunosorbent assay set-up (β-ME ELISA) and evaluated for VL diagnosis against outcome of reference freeze-dried DAT (FD-DAT) and rK39 strip test (RKT) commercial kits. Methods: Two-hundred and ninety-two sera from patients with high VL suspicion of whom 105 had confirmed L. donovani infection were tested. Results: Relatively higher sensitivities of 93.3% (95% CI: 88.4- 98.2) and 92.4% (95% CI: 87.3-97.5) were determined for β-ME ELISA and FD-DAT as compared to 83.8% (95% CI: 76.7-90.8) for RKT. Of 73 VL sera that scored maximum absorbance values (>0.81) in β-ME ELISA, 66 (90.4%) tested at the highest agglutination titres (>1:51200) in FD-DAT as did 56 (76.7%) also at comparable reaction intensities (3 + colour intensity) in RKT. Compared with FD-DAT (94.7%, 95% CI: 91.5-97.9) or RKT (93.0%, 95% CI: 89.3-96.6), lower specificity was estimated for β-ME ELISA (90.4%, 95% CI: 86.1-94.6). Based both on positive and negative microscopy for L. donovani in organ aspirates of all VL suspects enrolled (292), significantly higher correlation (p<0.01, 0.919) was established between β-ME ELISA and FD-DAT than between β-ME ELISA and RKT (p<0.01, 0.824). Taking into calculation the combined estimates of sensitivity, specificity, positive and negative predictive values, higher agreement (94.8%) was determined between total performance of β-ME ELISA and FD-DAT than between that of β-ME ELISA and RKT (90.7%). Conclusion: Based on results and merits discussed, we recommend application of this β-ME ELISA both for diagnosis of VL at laboratory level and confirmation of results obtained with DAT or RKT in the field.
Original Article
Zahra Amirghofran; Saeed Malek-Hosseini; Hossein Golmoghaddam; Fathollah Kalantar; Mehdi Shabani
Volume 8, Issue 3 , September 2011, Pages 159-169
Abstract
Background: A number of medicinal plants have been used to treat various immunological diseases. Nitric oxide (NO) has an important regulatory role in the various types of inflammatory processes. Objective: To investigate the NO modulatory activity of the extracts of several medicinal plants native to ...
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Background: A number of medicinal plants have been used to treat various immunological diseases. Nitric oxide (NO) has an important regulatory role in the various types of inflammatory processes. Objective: To investigate the NO modulatory activity of the extracts of several medicinal plants native to Iran including Dracocephalum kotschyi, Linum persicum, Dionysia termeana, Salvia mirzayanii, Ferulago angulata and Euphorbia cheiradenia. Methods: The methanolic extracts of the plants were prepared and examined for their effects on the NO production by lipopolysaccharide-stimulated mouse macrophages. The level of TNF-α and IL-1β proinflammatory cytokines in the macrophage culture were detected using enzyme-linked immunosorbent assay. Results: All the extracts at concentration of 50 μg/ml demonstrated a significant decrease in NO production (p<0.001) after a 24-hour treatment. This inhibitory effect was also seen after 48 hours. Among the extracts, L. persicum was the strongest extract in reducing the NO production at 1 μg/ml after both 24 and 48-hours (nearly 100% inhibition, p<0.001). S. mirzayanii extract with 66.2 ± 8% inhibition at 50 μg/ml, showed the mildest effects in 48 hour culture. In cytokine release determination, the extract of L. persicum significantly inhibited both TNF-α and IL-1β cytokines production by stimulated macrophages (p<0.001). D. kotschyi, D. termeana and F. angulata decreased secretion of IL-1β from the cells. Conclusion: These results indicate the presence of anti-inflammatory and macrophage inhibitory substances in these plants.
Original Article
Maryam Robati; Ardeshir Ranjbari; Mehri Ghafourian Boroujerdnia; Zahra Chinipardaz
Volume 8, Issue 3 , September 2011, Pages 170-175
Abstract
Background: Periodontitis is a multifactorial chronic inflammatory disease characterized by destruction of tooth-supporting tissues. Environmental and genetic factors as well as the immune system participate in this process. Recent studies have attempted to elucidate the role of cytokine networks involved ...
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Background: Periodontitis is a multifactorial chronic inflammatory disease characterized by destruction of tooth-supporting tissues. Environmental and genetic factors as well as the immune system participate in this process. Recent studies have attempted to elucidate the role of cytokine networks involved in periodontal diseases. Objective: To assess and compare the levels of IL-4, IL-6 and IL-12 in serum samples of patients with generalized aggressive periodontitis (GAgP) and control individuals. Methods: A total of 50 subjects were included in the study of which 25 patients had generalized aggressive periodontitis and 25 were healthy unrelated age and gender matched patients undergoing extraction and surgical crown lengthening (control group). Local blood samples of patients were collected from surgical sites of pocket reduction and from healthy individuals before tooth extraction or crown lengthening from non inflamed sites. The levels of IL-4, IL-6 and IL-12 were determined by an ELISA assay using serum samples separated from the whole blood of both groups. Results: The level of IL-4 increased significantly in control group in comparison with the test group (p=0.002). The amount of IL-6 in GAgP patients increased strongly compared with control group (p<0.0001). There was no significant difference between the two groups concerning the level of IL-12. Conclusion: There is an association between generalized aggressive periodontitis and low level of IL-4 as an anti-inflammatory cytokine, and high level of IL-6 as a proinflammatory cytokine. No correlation between IL-12 and generalized aggressive peridontitis was found.
Original Article
Shahriar Shahriari; Aliasghar Rezaei; Seyed Mohsen Jalazadeh; Khosro Mani; Alireza Zamani
Volume 8, Issue 3 , September 2011, Pages 176-182
Abstract
Background: Bone resorption is one of the main features of inflammatory periapical lesions and is mainly mediated by interleukin-1 beta (IL-1β), tumor necrosis factoralpha (TNF-α) and prostaglandin-E2 (PGE2). Recent investigations of these lesions revealed that pharmacological modulation may ...
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Background: Bone resorption is one of the main features of inflammatory periapical lesions and is mainly mediated by interleukin-1 beta (IL-1β), tumor necrosis factoralpha (TNF-α) and prostaglandin-E2 (PGE2). Recent investigations of these lesions revealed that pharmacological modulation may be possible. Objective: The aim of this study was to evaluate the effect of Ibuprofen on IL-1β, TNF-α and PGE2 levels in periapical exudates and compare the results with a group of placebo control. Methods: Thirty patients with non vital teeth and radiographic lesions were divided into two groups of case and control according to their entrance to the study. Periapical exudates were taken from root canals using absorbent paper points and followed by 400 mg Ibuprofen and placebo prescribed one tablet every 6 hour for three days and in the fourth day second samples were taken, then final cleaning, shaping and obturation of the canals were completed. IL-1β, TNF-α and PGE2 levels were determined by enzymelinked immunosorbent assays (ELISA). Data were analyzed using paired t-test and student's t-test. Results: The results showed that PGE2 levels were decreased significantly in the case group to 86.92 ± 72.42 Pg/ml following Ibuprofen treatment comparing with the pre-treatment (164.96 ± 12.255 Pg/ml) (p=0.02) and placebo group (154.2 ± 97.13 Pg/ml) (p=0.001). But there were no significant differences in IL-1β and TNF-α level between the two groups and in each group before and after treatment. Conclusion: The data indicate that Ibuprofen, as a non-steroidal anti-inflammatory drug (NSAID), can be used to block PGE2 release, enhance healing of inflammatory periapical lesions and possibly to inhibit bone resorption.
Original Article
Mojgan Mohammadi; Mohammad Mahdi Hayatbakhsh; Mohammad Javad Zahedi; Mohammad Reza Jalalpour; Amin Pakgohar
Volume 8, Issue 3 , September 2011, Pages 183-188
Abstract
Background: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative ...
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Background: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative colitis. Objective: We aimed to compare serum IL-23 level in patients with ulcerative colitis and normal controls and determine if serum IL-23 level increases with the severity of disease according to endoscopic findings. Methods: We quantified serum IL-23 levels from 60 patients with ulcerative colitis and 20 control individuals. All patients underwent endoscopic procedure to define the severity of disease. Patients were then stratified into 2 groups of "Mild" and "Severe" according to the endoscopic findings. Results: For comparison of serum IL-23 levels, Platelet count, ESR and CRP between the groups, Mann-Whitney U test and independent sample t test were employed, as appropriate. Pearson’s and spearman's correlation tests were employed to test the association of IL-23 with platelet count, CRP and ESR in patients. Our findings showed that serum IL-23 levels were increased in patients with ulcerative colitis compared to normal control. Moreover, patients in "Severe" group had higher serum IL-23 levels and ESR compared with those in "Mild" group. There was no significant sexual dimorphism in any of studied variables. Conclusion: We suggest that IL-23 plays an important role in the p
Short Paper
Batool Mutar Mahdi
Volume 8, Issue 3 , September 2011, Pages 189-194
Abstract
Background: Inflammatory bowel disease unclassified (IBDU) is considered to be an aberrant immune response with loss of tolerance to many antigens. Objective: This paper tries to address whether there is any value to test for auto-antibodies in such patients. Methods: 60 patients with inflammatory bowel ...
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Background: Inflammatory bowel disease unclassified (IBDU) is considered to be an aberrant immune response with loss of tolerance to many antigens. Objective: This paper tries to address whether there is any value to test for auto-antibodies in such patients. Methods: 60 patients with inflammatory bowel disease unclassified participated in the study. Auto-antibodies to nuclear antigen, intestinal goblet cell, exocrine part of pancreatic acinar cells, perinuclear antineutrophil cytoplasmic, cytoplasmic antineutrophil cytoplasmic and Saccharomyces cerevisiae were tested and compared to 20 ulcerative colitis (UC) patients and 30 healthy controls matched for age and sex. Results: There was a significant difference (p=0.000) between patients and control group in anti-exocrine part of pancreatic acinar cells, perinuclear antineutrophil cytoplasmic and Saccharomyces cerevisiae auto-antibodies. There was also a significant difference between IBDU and UC patients in the auto-antibodies directed against intestinal goblet cells, (p=0.000) exocrine part of pancreas (p=0.000) and anti Saccharomyces cerevisiae antibody (p=0.000). Conclusions: Due to the autoimmune nature of indeterminate colitis, involvement of some antigens from gastrointestinal tract or the bile system in the initiation of this disease is likely.
