Anna Hogendorf; Krystyna Wyka; Krzysztof Orczyk; Elzbieta Smolewska; Wojciech Mlynarski
Muhammad Hussain; Jiangshan Xiao; Yixuan Zhang; Peng Chen; Hongwu Du
Abstract
Background: Ribonucleoproteins particles that form the spliceosomes are among the most frequently targeted molecules of the autoimmune response. In the last few years, autoantibodies against all A/B hnRNP proteins have been found in the sera of patients with rheumatoid arthritis (RA), systemic lupus ...
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Background: Ribonucleoproteins particles that form the spliceosomes are among the most frequently targeted molecules of the autoimmune response. In the last few years, autoantibodies against all A/B hnRNP proteins have been found in the sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and serve as diagnostic markers for several rheumatic diseases. However, the functional role of hnRNP C1/C2 in autoimmune diseases is still not clearly understood. Objective: To identify hnRNP C1/C2 as an autoantigen in patients with Behcet’s Disease (BD). Methods: First, HaCaT and EA.hy926 cells were cultured and RNA was extracted. Second, amplification of the corresponding gene by RT-PCR, cloning, and purification techniques was applied to acquire the recombinant protein hnRNP C1/C2. Third, the target protein band was excised from gel electrophoresis, digested with trypsin, and analyzed by (MALDI-TOF/). Finally, Western blotting and ELISA were performed to verify the immunoreactivity of BD serum with recombinant hnRNPC1/C2. Results: Results demonstrated that the reactivity of BD serum against recombinant hnRNP C1/C2 protein was significantly higher as compared to healthy control (P<0.001). Conclusion: hnRNP C1/C2 can be considered as a self antigen which might be involved in BD pathology in Hans Chinese population.
Hamid-Reza Zare; Mojtaba Habibagahi; Akbar Vahdati; Zahra Habibagahi
Volume 12, Issue 3 , September 2015, , Pages 166-175
Abstract
Background: Patients with rheumatoid arthritis (RA) suffer from wide ranges of autoimmune reactions in joints. The mechanism of which is generally unknown and maybe associated with Treg deregulation. Objective: To compare the frequency of nTregs in peripheral blood of patients with active rheumatoid ...
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Background: Patients with rheumatoid arthritis (RA) suffer from wide ranges of autoimmune reactions in joints. The mechanism of which is generally unknown and maybe associated with Treg deregulation. Objective: To compare the frequency of nTregs in peripheral blood of patients with active rheumatoid disease with healthy individuals. Methods: Twenty five newly diagnosed patients with active RA disease were selected based on the clinical and laboratory criteria before starting their therapies. Treg cells in peripheral blood samples were enumerated by immune staining and flowcytometry analysis. Results: Clinical and laboratory results were in favor of active disease in all the studied patients although they showed variations in Disease Activity Score-28 (DAS-28). Compared to the healthy controls, RA patients had significantly lower frequency of CD4+ CD25hi or CD4+ CD25+ FoxP3+ natural regulatory T cells. In spite of that, there were no significant differences between patients and healthy controls in respect to the CD4/CD8 ratio. Interestingly, more CD4+ CD25- FoxP3+ cells were found in peripheral blood of patients. The frequencies of the Tregs did not show strong associations with the DAS-28. Conclusion: We showed lower abundance of nTregs in peripheral blood of RA patients which highlights the significance of these cells in RA.
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.
Abbas Ali Pourazar; Alireza Andalib; Farzad Qreizy; Hadi Karimzadeh; Ahmad Ghavami-Nejad; Behshad Pournasr-Khakbaz
Volume 2, Issue 2 , June 2005, , Pages 91-96
Abstract
Background: Inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect ...
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Background: Inappropriate activation or blockage of the inhibition of complement system could cause tissue damages in autoimmune diseases particularly rheumatoid arthritis (RA). Defect in complement component regulation may cause damages to tissues, on the other hand, or the damaged tissue might affect the unnecessary activation of complement components. Objective: To investigate the expression of CD55 and CD 59 complement regulatory proteins in RA patients. Subjects and Methods: Fifty proved rheumatoid arthritis patients participated in this study and their blood were collected for investigations. CD55 and CD59 molecules expression on the erythrocytes was assayed using primary monoclonal antibody and secondary FITC conjugated Ab, then the prepared samples were run with a FACSCalibur flowcytometer (Becton-Dickinson) and the obtained data was analyzed using a Cell Quest software package. To evaluate the complement function, CH50 was performed using patient sera. All experiments were done with a matched healthy volunteer group. Results: The mean fluorescence intensity for CD55 was 27.6 ± 13.4 arbitrary unit for patients and 68.5 ± 10.5 for healthy group. CD59 mean fluorescence intensity was 314 ± 83 in patient group and 508 ± 56 in healthy volunteers. In addition, there was a significant difference between CH50 in patients (54.5 ± 15.5) and in healthy group (110 ± 20). A significant correlation between CD55 and CD59 expansion on the patient erythrocytes was found (P = 0.00, r = 0.576). No association was found between CD59, or CD55 with CH50 (P > 0.05). Conclusion: The expression of CD55 and CD59 is down-regulated on erythrocytes of patients with RA. Change in expression of regulatory complement components in RA may be a useful key for the assessment of disease progression or in patients' follow-up.
