Evaluation of Inflammatory Markers in Patients with Depressed Episodes in Major Depressive Disorder and Bipolar Disorder before and after Treatment.

Depression is one of the current dilemmas in both developed and developing societies. Studies show that the severity of psychiatric symptoms is directly related to the degree of inflammation caused by cytokines secreted by the immune system. Hence, evaluating serum cytokine levels in patients with depression can help to understand the pathogenesis of the disease and make the best therapeutic decisions. The present study investigated the levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in patients with major depression or bipolar disorder during depressive episodes (BDDE) before and after a 6-month pharmaceutical intervention. Patients referring to 3 clinics were recruited for the study. The diagnosis of major depression or bipolar disorder in a depressive phase was made according to the Diagnostic and Statistical Manual of Mental Disorders -5(DSM-5) criteria. There was a significant difference in depression levels between the pre-intervention and 6-month follow-up in both groups. After 6 months, IL-1 and IL-6 levels in the bipolar disorder group had decreased while TNF-α levels had increased. There was also a significant difference between pre-intervention and follow-up levels of IL-1.  Serum levels of IL-1 and IL-6 decreased significantly in both groups after the 6-month follow-up, and symptom improvement was observed. TNF-α levels, on the other hand, decreased in the major depression group but increased in the bipolar disorder group. Considering that inflammation is a major outcome of depression, treatment strategies to reduce inflammation could be a practical approach to improving psychiatric symptoms.

Th17/Treg cell balance in stable liver transplant recipients.

BACKGROUND: Immune monitoring of transplanted patients may provide a reliable basis for the individualization of immunosuppressive therapy. In addition, it might be applied for realizing the early and non-invasive diagnosis of acute allograft rejection. METHODS: Percentages of TCD4 + IL-17+ (Th17) and TCD4 + CD25 + CD127dim/- (Treg) cells, as well as serum levels of interleukin (IL)-17 and transforming growth factor (TGF)-ß1, were evaluated in 30 stable patients using flow cytometry and ELISA techniques before and six months after liver transplantation. Besides, the same cells and cytokines were quantified in 10 recipients with acute allograft rejection. RESULTS: Six months post-transplant, the percentage of Th17 and Treg cells in the peripheral blood of stable liver transplant recipients reduced significantly, but the Th17/Treg ratios were comparable to the pre-transplant period (1.24 vs. 1.56); however, Th17/Treg ratios in the rejection group was significantly higher than in the stable recipients (4.06 vs. 1.56, P-value = 0.001). Stable patients showed decreased amounts of serum IL-17 which was remarkably lower than in the rejection group (P-value = 0.01). Moreover, there was a significant correlation between the serum level of IL-17 and the percentage of Th17 cells (P-value <0.001). Th17 frequency was negatively associated with the liver allograft function. Notably, TGF-ß1 levels differed neither between pre-and post-transplant samplings nor between stable and rejection groups. CONCLUSION: Six months after liver transplantation, the mean Th17/Treg ratio in stable recipients remained comparable to the pre-transplant values; however, it was significantly elevated in patients with acute allograft rejection, suggesting the Th17/Treg ratio as a probable predictor of acute rejection.

Comparing IRF-4 Gene Expression Between Acute T cell- Mediated Rejection and Stable Renal Transplant Recipients.

INTRODUCTION: Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules. METHODS: Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry. RESULTS: IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P < .05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population. CONCLUSION: IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.

Baricitinib: From Rheumatoid Arthritis to COVID-19.

Baricitinib is a JAK1/2 inhibitor that was first approved for treating moderate to severe rheumatoid arthritis (RA) but that later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. There is a growing body of evidence, obtained from clinical trials and case reports, demonstrating clinical and paraclinical improvement in patients following administration of baricitinib including RA, systemic lupus erythematosus, psoriasis, atopic dermatitis, alopecia areata, interferon-mediated autoinflammatory diseases, graft-versus-host disease, diabetic kidney disease, and, recently, coronavirus disease-19. However, despite overall encouraging results, many adverse effects have been observed in baricitinib-treated patients, ranging from simple infections to increased risk of malignancies, particularly in long-term use. The significant efficacy of baricitinib, versus the probable adverse effects, urge further investigation before establishing it as a part of standard therapeutic protocols. Here, we have provided a review of the studies that have used baricitinib for treating various inflammatory disorders and summarized the advantages and disadvantages of its administration.

Association of PTPN22 single nucleotide polymorphisms with chronic spontaneous urticaria

Introduction and objectives Chronic spontaneous urticaria (CSU) is thought to be an autoimmune disease in a subpopulation of patients. Protein tyrosine phosphatase-22 (PTPN22) polymorphisms are considered to be one of the strongest contributing factors to autoimmune diseases. In this study, we aimed to investigate the potential association of several PTPN22 single nucleotide polymorphisms (SNPs) with CSU in an Iranian population. Material and methods A total of 93 CSU patients and 100 healthy individuals were included in this study. Five SNPs within the PTPN22 gene were analyzed using TaqMan genotyping assays. The frequency of alleles, genotypes, and haplotypes of PTPN22 SNPs (rs12760457, rs2476601, rs1310182, rs1217414, and rs33996649) was investigated. Results A significantly higher prevalence of the rs1310182 T allele was observed among patients compared with controls [OR = 1.75 (95% CI: 1.17–2.63); P = 0.007]. In addition, the rs1310182 CC genotype and TT genotype were 0.47 and 2.06 times more common in patients, respectively (P = 0.03). Moreover, haplotype analysis demonstrated that CGCGC, CGTGC, and TGCGC (P < 0.001) were significantly associated with CSU. No significant differences were observed between the patients and controls in the other analyzed PTPN22 SNPs. Conclusions Polymorphisms of the PTPN22 gene are associated with an increased susceptibility to CSU in the studied Iranian population (AU)

Association of PTPN22 single nucleotide polymorphisms with chronic spontaneous urticaria.

INTRODUCTION AND OBJECTIVES: Chronic spontaneous urticaria (CSU) is thought to be an autoimmune disease in a subpopulation of patients. Protein tyrosine phosphatase-22 (PTPN22) polymorphisms are considered to be one of the strongest contributing factors to autoimmune diseases. In this study, we aimed to investigate the potential association of several PTPN22 single nucleotide polymorphisms (SNPs) with CSU in an Iranian population. MATERIAL AND METHODS: A total of 93 CSU patients and 100 healthy individuals were included in this study. Five SNPs within the PTPN22 gene were analyzed using TaqMan genotyping assays. The frequency of alleles, genotypes, and haplotypes of PTPN22 SNPs (rs12760457, rs2476601, rs1310182, rs1217414, and rs33996649) was investigated. RESULTS: A significantly higher prevalence of the rs1310182 T allele was observed among patients compared with controls [OR = 1.75 (95% CI: 1.17-2.63); P = 0.007]. In addition, the rs1310182 CC genotype and TT genotype were 0.47 and 2.06 times more common in patients, respectively (P = 0.03). Moreover, haplotype analysis demonstrated that CGCGC, CGTGC, and TGCGC (P < 0.001) were significantly associated with CSU. No significant differences were observed between the patients and controls in the other analyzed PTPN22 SNPs. CONCLUSIONS: Polymorphisms of the PTPN22 gene are associated with an increased susceptibility to CSU in the studied Iranian population.

Tocilizumab in transplantation.

PURPOSE: Tocilizumab, a monoclonal antibody directed against the IL-6 receptor, might block detrimental effects of IL-6 on transplantation. IL-6 plays a considerable role in cytokine storm after stem cell transplantation as well as graft versus host disease, and it has also been shown to be involved in solid organ allograft rejection; therefore, tocilizumab is expected to promote graft survival. Nonetheless, due to the small number of studies and disparate methods of drug administration and outcome evaluation, for which types of transplantation, at which stages, and to what extent tocilizumab could be applied remains to be defined. METHODS: The Pubmed, SCOPUS and Google Scholar search engines were used to collect data. The keywords were determined by Pubmed MeSH. No time limitation was set and all types of articles were allowed.  RESULTS: According to the potential of Tocilozumab in controlling both cellular and humoral immunity it could be considered as a promising agent in tolerance induction; however, blocking IL-6 signaling might result in augmented infection rate in recipients. CONCLUSION: The need for providing effective and safe immunosuppressive agents to protect transplanted cells and organs against allo-reactivity urges the collection and discussion of all available findings about inhibition of determining immune components including cytokines; herein, we have summarized the clinical consequences of blocking IL-6 by tocilizumab in stem cell and solid organ transplantations.