Potential roles of inflammasomes in the pathophysiology of Psoriasis: A comprehensive review.

Psoriasis is an inflammatory skin disease whose pathophysiology is attributed to both innate and adaptive immune cells and molecules. Despite the crucial roles of the immune system in psoriasis, it cannot be categorized as an autoimmune disease because of the lack of main signs of autoimmunity, such as specific antibodies, well-defined antigens, and autoimmune genetic risk factors. The presence of some cellular and molecular properties, such as the presence of neutrophils in skin lesions and the activation of the innate immune system, attributes psoriasis to a group of diseases called autoinflammatory disorders. Autoinflammatory diseases refer to a group of inherited disorders whose main manifestations are recurrent fever, a high level of acute-phase reactant, and a tendency for inflammation of the skin, joints, and other organs like the nervous system. In most autoinflammatory disorders, it has been seen that complexes of the high-molecular-weight protein named inflammasomes have significant roles. The inflammasome complex usually is formed and activated in the stimulated immune cell cytoplasm, and its activation consequently leads to inflammatory events such as producing of active caspase-1, mature interleukin-1ß (IL-1ß), and IL-18 and can cause an inflammatory programmed cell death called pyroptosis. Since the identification of inflammasomes, it has been shown that there are close links between them and hereditary and acquired autoinflammatory diseases like psoriasis. In this review, we aim to focus on well-defined inflammasome and their role in the pathophysiology of psoriasis.

Investigating the relationship between the number and activity of natural killer cells with increased cytomegalovirus and CMV disease after kidney transplantation.

BACKGROUND: Cytomegalovirus (CMV) infections caused by the cytomegalovirus are one of the most common problems in patients after kidney transplant. We examined the association of the relationship between the number and activity of natural killer cells with increased cytomegalovirus and its related disease after kidney transplantation. MATERIAL AND METHODS: In this analytical study, 58 new transplant patients in the Labbafinejad Hospital, who did not have any evidence of CMV infection, were evaluated based on the number and percentage of CD56+/16+, CD56+/16-, and CD69+ Natural Killer (NK) cells. RESULTS: The results of this study showed that CD16+ and CD56+ cells in the group of CMV Ag-positive patients are less than negative patients (p = 0.003) and the difference between the two groups are significant (p = 0.01). However, CD69+ cells did not differ significantly between the two groups (p = 0.1). Moreover, the absolute number of CD16+ and CD56+ cells declined significantly after infection with CMV unlike the CMV Ag - group(p = 0.003). DISCUSSION: These results indicate that kidney transplant patients suffering from CMV infection after transplantation have a significantly reduced total number of NK cells. On the other hand, a slight decrease in the number of NK subgroups was observed with an increase in the peak serum levels of cyclosporine. As a consequence of these findings, it can be assumed that more dosage and a higher level of the drug will result in more severe immunosuppression and, consequently, increased susceptibility to CMV infections. Thus, taking the right dose of the drug would prevent viral infections and immune system from over-activation.

Blood regulatory T cells in inflammatory bowel disease, a systematic review, and meta-analysis.

INTRODUCTION: Inflammatory bowel disease (IBD) is an autoimmune disease involving various parts of the gastrointestinal (GI) tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). Due to the contradictory results regarding the percentage of peripheral blood (PB) regulatory T cells (Tregs) in IBD patients, this meta-analysis aimed to determine the Tregs frequency in IBD patients. METHOD: We searched PubMed, Web of Science, SCOPUS, and Google Scholar databases for relevant observational articles that analyzed and reported the frequency of PB Tregs in IBD patients and healthy control groups. After choosing the related articles by two reviewers, the data regarding the definition of Tregs and their frequencies in different groups were recorded. RESULT: In 22 studies, the results showed a nonsignificant difference in the frequency of PB Tregs between IBD cases and control subjects (SMD: -0.27, 95 % CI: -0.78, 0.23). However, the frequency of CD4+CD25+CD127- (SMD: -0.89, 95 % CI: -1.52, -0.26) and CD4+CD25+FoxP3+ (SMD: -1.32, 95 % CI: -2.37, -0.26) Tregs were significantly lower in IBD cases, compared to healthy subjects. Also, UC cases and active IBD cases showed a significantly lower frequency of Treg cells, compared to controls and remission IBD cases, respectively (SMD: -0.68, 95 % CI: -1.24, -0.11 and SMD: -0.60, 95 % CI: -0.93, -0.27). CONCLUSION: Our study highlighted a probable decrease of Tregs in IBD patients, especially the patients with active states of the disease. The decrease of Treg cells might cause an imbalance in the immune system and the over-activation of auto-immune responses against the digestive tract.

The impact of killer cell immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA) class I ligands on predisposition or protection against prostate cancer.

Natural killer (NK) cell development largely depends on killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. In the current study, we investigated the role of KIR genes, HLA ligands, and KIR-HLA combinations in vulnerability or protection against prostate cancer (PC). To analyze the frequency of 16 KIR genes and 5 HLA ligands, polymerase chain reaction with sequence-specific primers (PCR-SSP) was conducted in 150 PC patients and 200 healthy controls (CNs). KIR2DL5 (p = 0.0346, OR = 0.606, CI = 0.3916-0.9336), KIR2DS5 (p = 0.0227, OR = 0.587, CI = 0.3793-0.9139), HLA-B Bw4Thr80 (p = 0.0401, OR = 0.3552, CI = 0.1466-0.9059), HLA Bw4 (p = 0.0190, OR = 0.4744, CI = 0.2656-0.8521), and T4 gene cluster (including KIR2DS5-2DL5-3DS1-2DS1 genes) (p = 0.0194, OR = 0.5575, CI = 0.3449-0.8938) had a lower frequency in the PC patients compared to the control group. Moreover, a lower frequency of the genotypes contacting activating KIR (aKIR) > inhibitory KIR (iKIR) (p = 0.0298, OR = 0.5291, CI = 0.3056-0.9174) and iKIR + HLA < aKIR + HLA (p = 0.0183, OR = 0.2197, CI = 0.0672-0.7001) in PC patients compared to the CNs implies a protective role for aKIR genes. In the case of KIR-HLA interactions, we detected a significant association between KIR3DS1+ + HLA-A Bw4+ (p = 0.0113, OR = 0.5093, CI = 0.3124-0.8416) and KIR3DL1- + HLA-A Bw4+ (p = 0.0306, OR = 0.1153, CI = 0.0106-0.6537) combinations and resistance to prostate cancer. In contrast, the presence of KIR3DL1 in the absence of HLA-A Bw4 (p = 0.0040, OR = 2.00, CI = 1.264-3.111), HLA Bw4 (p = 0.0296, OR = 2.066, CI = 1.094-3.906), and HLA-Bw4Thr80 (p = 0.0071, OR = 2.505, CI = 1.319-4.703) genes probably predisposes to prostate cancer. Carrying the CxT4 genotype in PC patients was positively associated with lower tumor grades (Gleason score ≤ 6) (p = 0.0331, OR = 3.290, and CI = 1.181-8.395). Altogether, our data suggest a protective role for aKIRs, HLA-B Bw4Thr80, and HLA Bw4 ligands as well as a predisposing role for certain KIR-HLA combinations in prostate cancer. The findings of this study offer new insight into the population's risk assessment for prostate cancer in men. Additionally, predicting immunotherapy response based on KIR-HLA combinations aids in implementing the most effective therapeutic approach in the early stages of the disease.

Isolation and in vitro Expansion of Regulatory T Cells from ß-Thalassemia Major Kids and in vitro Evaluation of Their Plasticity and Inhibitory Effects in the Presence of Pro-Inflammatory Cytokines.

INTRODUCTION: Graft-versus-host disease (GvHD) is a life-threatening syndrome commonly associated with hematopoietic stem cell transplantation (HSCT). Preventing the incidence of GVHD after HSCT along with minimizing long-term immunosuppression is currently under investigation with regulatory T cells (Tregs). As Tregs are a low-frequency population and the yield of all memory Tregs is not sufficient for clinical application, an initial Treg expansion is essential. METHODS: Thirty milliliters of peripheral blood from the ß-thalassemia major (beta-TM) patients and healthy controls were obtained and Tregs were isolated using MACS. Isolated cells were cultured in the presence of rapamycin and rIL-2 followed by activated with anti-CD3/CD28-coated beads. To evaluate Treg plasticity, expanded Tregs were cultured in a medium containing IL1ß, IL6, TGFß, and IL2, with or without 500 nM rapamycin for 72 h. To assess the functional properties of Tregs, CFSE dilution assays were performed to evaluate the ability of in vivo expanded Tregs from beta-TM patients. Statistical analysis was performed using paired t-test and independent t-test, with the aid of SPSS version 12.0. p-value ≤0.05 was considered significant. RESULTS: The percentage of Tregs isolated from the control group was significantly higher than the Tregs isolated from patients (p-value = 0.01), which is probably due to the iron overload in beta-TM patients as a result of continuous blood transfusion. Also, the percentage of Tregs after 5 days of expansion had a significant increase in both groups compared to before expansion (p-value = 0.03). Our results also showed that the expansion of Tregs after 72 h in the presence of inflammatory cytokines and in the absence of rapamycin led to the increase in the intracellular expression of IL-17 (p-value = 0.01), while intracellular expression of IL-17 remained low following the addition of 100 nM rapamycin to the culture medium (pvalue = 0.073). The results of the functional evaluation of expanded Tregs showed relatively differences in both patient and control groups. Thus, expanded Tregs inhibited the proliferation of responder T cells in a dose-dependent manner in the control group (p-value = 0.028), while in the patient group this inhibitory effect was not significant (p-value = 0.055). CONCLUSION: Tregs isolated from beta-TM patients have poorer inhibitory performance than Tregs isolated from healthy individuals. Also, we concluded that rapamycin stabilizes the Treg population by inhibiting the production of IL-17, all necessitating the administration of appropriate immunosuppressive drugs in patients receiving Treg therapy.

Frequency of CD39+, LAG3+, and CTLA4+ Regulatory T Cells in Two Different Immunosuppressive Protocols in Renal Allograft Recipients (Sirolimus vs Mycophenolate mofetil): A Cohort Report.

BACKGROUND: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies. OBJECTIVE: This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients. METHODS: Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation. RESULTS: Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation. CONCLUSIONS: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.

Natural killer cells and killer cell immunoglobulin-like receptors in solid organ transplantation: Protectors or opponents?

Among all the cells of innate immunity, natural killer (NK) cells are well-known for the fight against tumors and virally-infected cells. NK cells have been implicated in the pathogenesis of immune-mediated allograft damage, but mounting evidence suggests they can potentially promote allograft tolerance as well. In addition, NK cells express a wide variety of activating and inhibiting receptors, and the signals sent by these molecules, particularly killer cell immunoglobulin-like receptors (KIRs), determine their ultimate function. The role of KIRs and their human leukocyte antigen (HLA) class I ligands have been extensively investigated in hematopoietic stem cell transplantation (HSCT). Previous studies have suggested that, in the setting of solid organ transplantation, having certain KIR genes or KIR/HLA combinations probably affects allograft survival. Therefore, it may be helpful to analyze KIR/HLA combinations in donors and recipients to choose the optimal donor, anticipate harmful effects post-transplantation, and develop NK cell-based immunotherapies to enhance the success of solid organ transplantation. In this review, we will discuss the dual function of NK cells in solid organ transplantation, followed by a brief introduction to KIRs and the association of KIR and HLA genes with kidney, liver, and lung transplant outcomes.

The Efficacy of a New Protocol of Oral Immunotherapy to Wheat for Desensitization and Induction of Tolerance.

Oral immunotherapy (OIT) is a novel approach to desensitization and tolerance induction in food allergy patients. This study aimed to design and implement a new wheat OIT protocol, evaluate its efficacy in tolerance induction, and assess specific immunoglobulin-E (IgE) and regulatory T cell changes. From 2015 to 2017, 26 patients with confirmed IgE-mediated hypersensitivity to wheat were treated via oral immunotherapy (OIT). Patients with prior anaphylactic episodes underwent OIT using the rush method. Specific IgE concentrations and the number of regulatory T cells (CD4+ CD25+ FOXP3+ T cells) were measured using Allergy Screen immunoblot assay and flow cytometry, respectively. This study was registered in the Iranian Registry of Clinical Trials (IRCT20181220042066N1). The results revealed success rates of 100% and 93.3% for desensitization and tolerance. Specific IgE was significantly reduced after 12 months of OIT. No significant change in regulatory T cell numbers was observed. In view of the promising findings of this study, the proposed OIT protocol could be viewed as an effective and valuable method to induce tolerance and desensitization in wheat allergic patients.

Association of IL-15 and IP-10 Serum Levels with Cytomegalovirus Infection, CMV Viral Load and Cyclosporine Level after Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection is the most common complications following kidney transplantation. Natural killer (NK) cells demonstrated critical anti-viral role in controlling and elimination of CMV after transplantation. Interleukin-15 (IL-15) is a pleiotropic cytokine that promotes the activity of NK cells and strengthens the acquired immune system. Also, IP10 (CXCL10) is a chemotactic factor which regulates NK cell recruitment and antiviral immune response. We aimed to determine the correlation between the serum levels of IL-15 and IP-10 cytokines with CMV infection, CMV viral load, and cyclosporine as a major immunosuppressive treatment after transplantation. METHODS: Fifty-eight kidney transplant recipient patients without evidence of CMV virus disease before transplantation surgery were included in the study. From the day of transplant surgery, the patients were evaluated based on the presence of CMV Ag pp65, CMV viral load, serum levels of IL-15 & IP-10, Cyclosporine levels (C0 & C2), Glomerular Filtration Rate (GFR), and hematological & biochemical Index, up to 75 days. RESULTS: Comparison analysis of serum levels of IL-15 and IP-10 showed no significant association with CMV infection in kidney transplant recipients. In addition, CMV viral load and cyclosporine levels at C0 and C2 did not affect patients' IL-15 and IP-10 levels. CONCLUSION: The levels of IP-10 and IL-15 cytokines are not affected with CMV infection, even if a viral infection occurs in the early days after transplantation or long afterwards. In addition, taking the different levels of cyclosporine did not affect the cytokines levels. Other mechanisms may play a role in maintaining the levels of these cytokines.

Association of HLA Class II Alleles with Disease Severity and Treatment Response in Iranian Patients with Myasthenia Gravis.

Myasthenia gravis is an autoimmune neuromuscular disease with a multifactorial etiology. A major part of the genetic susceptibility belongs to the HLA encoding genes. In this study, we investigated the role of HLA class II polymorphism in disease severity, and treatment response. In our 146 patients, 15 DRB1, 7 DQA1, and 9 DQB1 alleles, and 19 haplotypes were found. Adjusted p-values did not show any significant associations between these loci, disease severity and treatment outcome. Further studies in different populations with a larger number of patients are needed to determine the exact contribution of HLA class II alleles to MG prognosis.

Cell therapy in transplantation: A comprehensive review of the current applications of cell therapy in transplant patients with the focus on Tregs, CAR Tregs, and Mesenchymal stem cells.

Organ transplantation is a practical treatment for patients with end-stage organ failure. Despite the advances in short-term graft survival, long-term graft survival remains the main challenge considering the increased mortality and morbidity associated with chronic rejection and the toxicity of immunosuppressive drugs. Since a novel therapeutic strategy to induce allograft tolerance seems urgent, focusing on developing novel and safe approaches to prolong graft survival is one of the main goals of transplant investigators. Researchers in the field of organ transplantation are interested in suppressing or optimizing the immune responses by focusing on immune cells including mesenchymal stem cells (MSCs), polyclonal regulatory Tcells (Tregs), and antigen-specific Tregs engineered with chimeric antigen receptors (CAR Tregs). We review the mechanistic pathways, phenotypic and functional characteristics of these cells, and their promising application in organ transplantation.

Serological and Molecular Tests for COVID-19: a recent update.

The COVID-19 pandemic is probably the most devastating worldwide challenge in recent century. COVID-19 leads to a mild to severe respiratory disease and affects different organs and has become a global concern since December 2019. Meanwhile, molecular biology and diagnostic laboratories played an essential role in diagnosis of the disease by introducing serological and molecular tests. Molecular-based techniques are reliable detection tools for SARS-CoV-2 and used for diagnosis of patients especially in the early stage of the disease. While, serological assays are considered as additional tools to verify the asymptomatic infections, tracing previous contacts of individuals, vaccine efficacy, and study the seroprevalance. The average time of the appearance of anti-SARS-CoV-2 antibodies in the patient's serum is 3-6 days after the onset of symptoms for both IgM and IgA and 10-18 days for IgG. Following the outbreak of COVID-19, FDA has approved and authorized a series of serological laboratory tests for early diagnosis. Serological assays have low-cost and provide fast results but have poor sensitivity in the early stage of the viral infection. Although the serological tests may not play an important role in the active case of COVID-19, it could be effective to determine the immunity of health care workers, and confirm late COVID-19 cases during the outbreak. In this review, we compared various laboratory diagnostic assays for COVID-19.

Investigating the Role of BAFF and Its Receptors in Renal Transplant Recipients with Chronic Antibody-Mediated Rejection.

BACKGROUND: Kidney transplantation is the best treatment option for end stage renal disease (ESRD), but graft rejection is still a big obstacle that occurs in spite of immunosuppressive therapy. B cells are considered as the major reason for renal graft rejection because of antibody production. Due to their roles in B cell function, we intended to evaluate the B cell activating factor (BAFF) and its receptors including BAFF receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and cyclophilin ligand interactor (TACI) in renal transplant patients. METHOD: The study included 40 kidney allograft patients with cAMR, 40 stable kidney allograft patients, and 8 healthy volunteers with normal kidney function. The percentage and absolute number of CD19+ B cells were analyzed by flow cytometry, the serum level of BAFF was analyzed by ELISA, and mRNA expressions of BAFF and BAFF receptors (BAFF-R, BCMA, and TACI) were measured using quantitative real-time PCR. RESULTS: The percentage and the absolute number of B cells decreased significantly in stable and cAMR patients compared to healthy individuals. The serum level and gene expression of BAFF, as well as the mRNA level of BCMA, were increased significantly in both cAMR and stable patients compared to healthy volunteers. There was an overexpression of TACI mRNA in cAMR patients compared to stable patients. CONCLUSIONS: Both soluble protein and mRNA transcript of BAFF increased in transplant recipients. However, BAFF neither at the serum level nor at the mRNA transcript level cannot be a good biomarker for the prediction of cAMR. In addition, expression of TACI, compared to other receptors of BAFF, confers a potential to be used in distinguishing cAMR and stable kidney transplant patients.

B cell modulation strategies in the improvement of transplantation outcomes.

Successful transplantation outcome is the final goal in most end stage and nonfunctional organs; however, despite using different therapeutic strategies, antibody-mediated rejection is still a big obstacle. B cells have a key role in transplant rejection by several functions, such as antibody production, antigen presenting, contribution in T cell activation, forming the germinal center, and tertiary lymphoid organs. Therefore, B cells modulation seems to be very crucial in transplant outcome. A double-edged sword function is considered for B cells during transplantation; On the one hand, antibody production against the transplanted organ induces antibody-mediated rejection. On the other hand, IL10 production by regulatory B (Breg) cells induces graft tolerance. Nowadays, several monoclonal antibodies (mAb) are available for B cell modulation that are routinely used in transplant recipients, among which rituximab (anti-CD20 mAb) act in eliminating B cells. However, there are some other monoclonal antibodies, such as epratuzumab and Inotuzumab ozogamicin (IO), which exert anti-CD22 activity, resulting in disruption of B cell functions and induction of tolerance in autoimmune disease or B cell malignancies; that notwithstanding, these mAbs have not yet been tried in transplantation. In this review, we focus on different methods for modulating the activity of B cells as well as induction of Breg cells, aiming to prevent the allograft rejection.

Human leukocyte antigen class I (A, B) and class II (DRB1) allele and haplotype frequencies in Iranian patients with Buerger's disease.

OBJECTIVE: The aim of this study was to investigate the human leukocyte antigen (HLA) class I (HLA-A and HLA-B) and II (HLA-DRB1) allele and haplotype frequencies in a group of Iranian patients with Buerger's disease (BD) in comparison with a normal healthy control group. METHODS: A total of 70 unrelated male patients and 100 healthy controls from Sina Hospital, Tehran, Iran, belonging to the same ethnic background, were enrolled in this case-control study. HLA-A, B, and DRB1 typing were performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). RESULTS: The results of this case-control study showed that the frequency of the HLA-A*03:01 (odds ratio (OR) = 2.88, P value (Pv) = .002), HLA-A*29:01 (OR = 15.31, Pv < .001), HLA-DRB1*04:02 (OR = 3.41, Pv < .001), and HLA-DRB1*16:01 (OR = 8.16, Pv < .001) was significantly higher in BD patients compared with healthy controls, whereas the frequency of the HLA-DRB1*01:01 (OR = 0.03, Pv < .001) was significantly lower in BD patients. The most frequent extended haplotypes in our patients were HLA-A*02:01-B*55:01-DRB1*04:03. CONCLUSION: This study is the first study evaluating an association between the HLA pattern and BD in the patients with BD from North West and North Iran.

IL-27 and autoimmune rheumatologic diseases: The good, the bad, and the ugly.

The footprint of cytokines is evident in almost every biological process, such as development, as well as the pathogenesis of the different diseases, immune responses to pathogens, etc. These small proteins are categorized into different functional classes; for instance, they can play a pro-inflammatory or anti-inflammatory role in different situations, or they can confer a polarization to the immune system. Interleukin (IL)-27 is a member of the IL-12 family. Antigen-presenting cells are the primary source of IL-27 production, which exerts its effects by bindings to the IL-27 receptor expressed on the surface of target cells. Interaction of IL-27 and IL-27 receptor leads to activation of the JAK-STAT and p38 MAPK signaling pathways. Most studies focused on the inflammatory effects of this cytokine, but gradually anti-inflammatory effects were also revealed for this cytokine, which changed the traditional perception of the function of this cytokine. The functionality of IL-27 in the pathogenesis of rheumatic diseases has been attributed to a double-blade sword. Hence, novel therapeutic approaches have been devised targeting IL-12 family that has been accompanied with promising results. In this review, we focused on the inflammatory and anti-inflammatory properties of IL-27 in different autoimmune rheumatologic diseases and its plausible therapeutic potentials.

Intravenous Immunoglobulin Therapy in Myocarditis.

Myocarditis is an inflammatory disease of the myocardium with lymphocyte infiltration and myocyte necrosis leading to a wide range of clinical presentations including heart failure, arrhythmia, and cardiogenic shock. Infectious and noninfectious agents may trigger the disease. The fact that immunosuppressive drugs are useful in several kinds of autoimmune myocarditis is proof of the autoimmune mechanisms involved in the development of myocarditis. Pathogenic mechanisms in myocardial inflammation are including inflammasome activation followed by myocyte destruction, myocarditis, and pericarditis. Intravenous immunoglobulin (IVIG) is a serum product made up of immunoglobulins, widely used in a variety of diseases. This product is effective in several immune-mediated pathologies. As well as the determined usage of IVIG in Kawasaki disease, IVIG may be useful in several kinds of heart failure including fulminant myocarditis, acute inflammatory cardiomyopathy, Giant Cell Myocarditis, and peripartum cardiomyopathy. Generally, IVIG is used in two different doses of low dose (200 to 400 mg/kg) and high dose (2 g/kg) regimen. The exact therapeutic effects of IVIG are not clear, however over the last decades, our knowledge about its mechanism of function has greatly enhanced. IVIG administration should be based on the accepted protocols of its transfusion. In this review article, we try to provide an overview of the different kinds of myocarditis, pathologic mechanisms and their common treatments and evaluation of the administration of IVIG in these diseases. Furthermore, we will review current protocols using IVIG in each disease individually.

Dynamic variation of kidney injury molecule-1 mRNA and protein expression in blood and urine of renal transplant recipients: a cohort study.

BACKGROUND: Acute renal dysfunction still constitutes a highly significant obstacle to renal transplantation outcome. Kidney injury molecule-1 is highly upregulated in proximal tubular cells and shed into the urine and blood circulation following kidney injury. The aim of current cohort study was to evaluate the urine KIM-1 (uKIM-1) mRNA expression level and its protein concentration in blood and urine samples to determine whether sequential monitoring of KIM-1 in renal allograft recipients is a reliable biomarker for predicting the clinical status and outcome. METHODS: Both uKIM-1 mRNA expression level and the level of serum and uKIM-1 protein concentration in the 52 renal transplant recipients were respectively quantified using real-time PCR and ELISA methods at 2, 90 and 180 days after transplantation. RESULT: KIM-1 mRNA and protein expression level in the blood and urine samples of patients with graft dysfunction was significantly higher than patients with well-functioning graft on days 2, 90 and 180 after transplantation. Receiver-operating characteristic curve analysis of mRNA and protein expression levels showed that urinary and blood KIM-1 at months 3 and 6 could predict acute renal dysfunction at 6 months and 1 year after transplantation. CONCLUSION: Sequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury.

TLR-2, TLR-4 and MyD88 genes expression in renal transplant acute and chronic rejections.

BACKGROUND: Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll-like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. METHODS: In present research, we have evaluated the mRNA expressions of TLR-4, TLR-2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T-cell-mediated rejection (ACMR), six acute antibody-mediated rejection (AAMR), 10 chronic T-cell-mediated rejection (CCMR) and four chronic antibody-mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real-time polymerase chain reaction (RT-PCR). RESULTS: It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. CONCLUSION: These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell-mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.

TIM family gene polymorphism and susceptibility to rheumatoid arthritis: Systematic review and meta-analysis.

BACKGROUND: TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944. METHODS: A systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models. RESULTS: A total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43-2.61) and allelic models (OR, 1.74, 95% CI, 1.31-2.30). None of the other examined polymorphisms indicated significant association with RA. CONCLUSIONS: The present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings.