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Although the precise nature of Antiphospholipid antibodies is still not clearly defined, they are known to have association with thromboembolic events and have been found in hepatitis C virus (HCV) infection. Moreover, high prevalence of HCV infection and thrombotic risk is described in thalassemia. We aimed at investigating the prevalence of anticardiolipin antibodies (aCLAbs), lupus anticoagulant (LA), and their relation with HCV infection in Iranian thalassemic patients. Presence of anti-HCV antibody, serum HCV-RNA, aCLAbs, and LA activity was determined in 131 patients with thalassemia major (male/female: 63/68 aged 3–29 years) registered at thalassemia unit, Dastgheib Hospital, Shiraz, Iran. Sixty-one healthy controls were also included. Anti-HCV antibody was positive in 24 (18.3%), IgG aCLAbs in 56 (42.7%), and LA activity in 9 (6.9%) patients. 87.5% of patients positive for aCLAbs had a low titer of aCLAbs. Although none of the participants had a previous history of thrombosis, higher prevalence of aCLAbs was detected in thalassemic patients compared with controls. No significant difference in the prevalence of aCLAbs was found between HCV-infected and noninfected patients. A high prevalence of aCLAbs, the majority in low titers, was detected in Iranian thalassemic patients irrespective of previous history of thrombosis and presence of HCV infection. [ABSTRACT FROM AUTHOR]

Background: Behçet's Disease (BD) is a chronic autoimmune disease with unknown etiology. Adipokines due to their roles in the regulation of immune responses might be important in the induction and progression of BD., Subjects and Methods: This case-control study included 340 patients with BD and 310 healthy controls. Single nucleotide polymorphisms (SNPs) in adiponectin (rs266729 and rs1501299) and leptin (rs7799039 and rs2167270) genes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum levels of adipokines were measured using enzyme-linked immunosorbent assay (ELISA)., Results: A higher frequency of leptin rs7799039 GG, AG, and AG +GG genotypes and G allele was revealed in patients. Besides, patients had more leptin rs2167270 AG and AG +AA genotypes and A allele. Furthermore, rs2167270 AA genotype and A allele were more frequently seen in total and female patients who had genital aphthous. Patients had significantly more serum levels of adiponectin while those with genital aphthous had significantly more leptin levels. No significant association was observed between genotypes and alleles of adiponectin SNPs and BD., Conclusion: Our findings indicated that leptin gene polymorphisms might predispose Iranian individuals to BD. Besides, elevated serum levels of adiponectin might facilitate BD pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Behcet's disease (BD) is a systemic vasculitis, characterized by recurrent oral aphthous, genital ulcers, ocular lesions, and other organ involvement. Interleukin (IL)-27 with its pro- and anti-inflammatory effects might be an important effective cytokine in this disease. The aim of this study was to investigate the association of IL-27 serum concentration and a single-nucleotide polymorphism (SNP) rs153109 (-964 A > G) with the risk and clinical features of the patients with BD. IL-27 Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the IL-27 serum levels were measured using enzyme-linked immunosorbent assay (ELISA). It is shown that AG, GG, and AG + GG genotypes, as well as G allele of rs153109, can significantly increase the risk of BD in total and in male individuals. Significantly higher frequencies of AG and GG genotypes and G allele were observed in total and male patients with an active form of BD. AG and GG genotypes were associated with joint (p = 0.046) and vascular (p = 0.02) involvement. The frequency of the G allele was higher in all patients, as well as in female patients with vascular involvement (p = 0.02). Serum cytokine analysis indicated an increased level of IL-27 in BD patients compared to healthy subjects (p = 0.038). Additionally, a higher level of IL-27 was detected in patients carrying the rs153109 GG genotype (p = 0.04) and those with renal (p = 0.009) and skin (p = 0.05) involvement. In conclusion, this study underscores the involvement of IL-27 rs153109 variants and increased serum level in BD susceptibility and pathogenesis.

Rheumatoid arthritis (RA) is a complex disease, the hallmark of which is synovial joint inflammation. The substantial contribution from genetic factors in susceptibility to RA has been well-defined. The Fc receptor-like3 (FCRL3) gene is one of the genes that have recently shown a significant association with RA. To determine the possible role of FCRL3-169 C/T and FCRL3-110 A/G gene polymorphisms in the development of RA in Iranian patients, 320 RA patients and 302 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. No significant difference was found in genotype and allele frequencies of FCRL3-169 C/T between patients and controls. In contrast, at position -110 A/G, the frequency of the AA genotype and A allele was significantly decreased in RA patients compared to controls (p = 0.005). After Bonferroni correction for multiple testing, no significant correlations between FCRL3-169 C/T and -110 A/G polymorphism and laboratory and clinical features of the patients was observed. In conclusion, the results of this study showed a significant association between FCRL3-110 A/G polymorphism and susceptibility to RA.

Interleukin 6 (IL-6) has been shown to be related to the pathogenesis of systemic lupus erythematosus (SLE). In the present study, the relationship between two polymorphisms in the promoter region of IL-6 gene at positions -572 G/C and -174 G/C and disease susceptibility in 401 Iranian patients with SLE was investigated using polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution and allele frequencies of IL-6 gene polymorphism at -174 position showed no significant difference between SLE patients and controls. In contrary, both allelic and genotypic frequencies at the -572 position significantly differed in SLE patients and controls. At this position, GG genotype was observed in 77.9% of patients compared to 68.9% in the control group (p < 0.014). The frequency of -572 G allele in patients (87.3%) was also higher than in controls (83.2%; p = 0.034). The haplotype study showed no significant difference between patients and healthy subjects. Study of the relationship between these polymorphisms and clinical manifestations and laboratory parameters showed an association between -174 polymorphism and the presence of antinuclear antibodies in all patients and rash and hematuria in male patients (p < 0.04). At -572 polymorphism, a significant difference with regard to photosensitivity in male patients (p = 0.04) was found. In conclusion, results of this study showed that -572 polymorphism plays an important role in susceptibility to SLE and that -174 polymorphism could influence the presence of antinuclear antibodies in the patients.

Immunomodulation using medicinal plants provides an alternative to conventional chemotherapy for several diseases, especially when suppression of inflammation is desired. The "Canon of Medicine", the epochal work of Avicenna, the great Persian scientist of the middle ages, provides comprehensive information about medicinal plants which used to cure inflammatory illnesses in traditional Iranian medicine. Taking into consideration that the mechanisms of damage in these illnesses are mediated by immune responses, it is reasonable to assume that the plants used for such diseases may suppress the immune responses and the resultant inflammation. In Iran, because of great diversity of climate and geographical conditions, numerous varieties of plants grow and at least 1000 species are recorded as medicinal plants. Many of these plants such as Punica granatum, Glycyrrhiza glabra, Foeniculum vulgare and Polygonum species prescribed by ancient Iranian physicians have been shown to possess anti-inflammatory and immunomodulatory effects. In recent literature, different species of native medicinal plants such as Stachys obtusicrena, Salvia mirzayanii, Echium amoenum, Dracocephalum kotschyi and Linum persicum have been shown to have appreciable anti-inflammatory and immunomodulatory effects including inhibitory effects on lymphocyte activation, suppression of cellular and humoral immunity and induction of apoptosis. This review focuses on plants that are used in Iranian traditional medicine and have been reported to act as immunoinhibitory agents.

TGF-beta1 is a multifunctional cytokine that acts as both a tumor suppressor and a stimulator of tumor progression. Susceptibility to colorectal carcinoma may be affected by genetic factors. In this study, the association between -800 G/A and -509 C/T polymorphisms of the transforming growth factor beta1 gene, TGFB1, and susceptibility to colorectal cancer in Iranian patients was investigated. This study was conducted with 134 patients with colorectal carcinoma and 138 healthy controls matched for age and sex. Genotyping was performed on genomic DNA using polymerase chain reaction and restriction fragment length polymorphism. The genotype distributions and allele frequencies of the TGFB1 gene polymorphism at -509 C/T were significantly related to colorectal carcinoma. A lower frequency of 509T allele (41.8%) and TT genotype was observed in patients (21.6%) than in control subjects (52.9% and 29.7%, respectively) (P<0.035). At position 800, no significant differences in genotype distribution and allele frequencies between the patients and healthy controls was found (P>0.05). These data suggest that the genetic polymorphism at -509 C/T but not at -800 G/A of the TGFB1 gene may play a role in susceptibility of Iranian subjects for colorectal carcinoma.

In this study, the immunologic abnormalities of Iranian beta-thalassemia major patients were characterized, considering their clinical parameters including splenectomy status and iron overload. Serum samples and peripheral blood mononuclear cells were collected from 28 patients and 30 age- and sex-matched healthy individuals. Patients with thalassemia showed significantly increased absolute lymphocyte counts compared with the control group. An increased number of activated T cells and higher levels of serum neopterin were also observed in thalassemia patients, which suggest chronic stimulation of immune system. On the contrary, T-cell proliferation and interleukin 2 (IL-2), interferon gamma (IFN-gamma), and IL-4 production were suppressed in patients compared to controls. Patients with high serum ferritin levels produced significantly less IFN-gamma and IL-2, indicating the immunosuppressive effect of iron overload in beta-thalassemia patients. The serum levels of tumor necrosis factor alpha and absolute counts and percentages of B and T cells were higher in splenectomized patients; however, serum levels of neopterin significantly decreased in splenectomized patients compared to the non-splenectomized group. Taken together, T lymphocytes express activated phenotype in polytransfused beta-thalassemia major patients, while T cell proliferation and effector function are significantly suppressed. Multiple blood transfusion and continuous immune stimulation could be responsible for making such a double-faced immune response.

In this study the antineoplastic activity of methanolic extracts of six medicinal plants that are native to Iran, including Galium mite, Ferulago angulata, Stachys obtusicrena, Cirsium bracteosum and Echinophora cinerea was investigated. Different tumor cell lines were exposed to the extracts and cytotoxic analysis using MTT colorimetric assay was performed. Quantification of percentage of cells undergoing apoptotic changes by flow cytometry, and DNA fragmentation analysis on sensitive cell lines was then carried out. Results obtained indicated that almost all of the extracts more or less had the capacity to decrease the proliferation of tumor cells. Among the plants, the highest activity against K562 leukemia cell line was found for E. cinerea and C. bracteosum with IC50 less than 20 microg/ml followed by G. mite with IC50 of 39.8 microg/ml. F. angulata and E. cinerea, mostly inhibited Jurkat cells proliferation (IC50 less than 8 microg/ml). Fifty percent inhibition of Fen bladder cell carcinoma due to exposure to F. angulata and E. cinerea was found at concentrations of nearly 180 microg/ml. A549, a lung carcinoma cell, was mostly affected by S. obtusicrena (IC50 more than 200 microg/ml). In flow cytometry analysis, C. bracteosum, E. cinerea, F. angulata and S. obtusicrena extracts demonstrated no remarkable effects on the cell cycle profile of K562 and Jurkat cells. Moreover, in DNA fragmentation analysis of treated cells, no ladder formation was detected. In contrary, G. mite caused more than 40% apoptosis in the K562 and Jurkat cells. In DNA fragmentation analysis G. mite extract produced ladder formation in these cells. In conclusion, these results indicated that the extracts used in this study have anti tumor activity particularly against the leukemia cell lines and that apoptosis is the possible cause of cell death observed due to the extract of G. mite.

A group of medicinal plants including, Silybum marianum, Matricaria chamomilla, Calendula officinalis, Cichorium intybus and Dracocephalum kotschyi which grow in Iran, were extracted with ethanol 70% and the mitogenic activity was examined both on human peripheral blood lymphocytes and thymocytes. Effect of these extracts on proliferative responsiveness of human lymphocytes to phytohemagglutinin (PHA) and on the mixed lymphocyte reaction (MLR) was also investigated. The results obtained indicated that none of the extracts had a direct mitogenic effect on human lymphocytes or thymocytes (stimulation index, SI<0.07). Among the plants studied, C. intybus and C. officinalis showed a complete inhibitory effect on the proliferation of lymphocytes in the presence of PHA (SI range 0.01-0.49). A dose dependent inhibitory effect was obtained in the case of D. kotschyi. Extract of M. chamomilla showed almost no stimulatory effect. A significant decrease in proliferation assay due to 0.1-10 microg/ml of S. marianum was observed (SI<0.46, P<0.05). In MLR, a markedly stimulatory effect with some lower concentrations of all the extracts except Dracocephalum was detected. The highest stimulatory effect was due to 100 microg/ml of S. marianum (SI 2.82). Treatment of mixed lymphocytes with 0.1-10 microg/ml of C. officinalis (SI range 1.34-1.80) and 10 microg/ml of M. chamomilla and C. intybus (SI 2.18 and 1.70, respectively) strongly increased the cell proliferation. In conclusion, this in vitro study revealed the capacity of all the extracts except Dracocephalum to enhance the proliferation of lymphocytes after stimulation with the allogenic cells.