The investigation of relevancy between PIAS1 and PIAS2 gene expression and disease severity of multiple sclerosis.

Introduction: PIAS1 and PIAS2 (protein inhibitor of activated STAT 1,2) play key roles in the pathogenesis of autoimmune and inflammatory diseases. This study aims to evaluate the gene expression of these factors in multiple sclerosis (MS) patients compared to healthy individuals and correlate them with the severity of MS. Materials and methods: Sixty participants, including 30 patients with MS and 30 healthy controls were studied. The expression of PIAS1 and PIAS2 genes in peripheral blood samples of all participants was measured by real-time PCR. The severity of MS was evaluated using the Expanded Disability Status Scale (EDSS). Finally, we evaluated the correlation between the expression of PIAS1 and PIAS2 genes with disease severity. Results: The expression of PIAS1 gene was increased in patients with MS compared to healthy subjects (P value<.001). Also, there was a significant correlation between the expression of PIAS1 and PIAS2 genes with disease severity according to EDSS. Conclusion: Our study suggests the expression of PIAS1 and PIAS2 genes as a prognostic and diagnostic marker in MS disease.

Correlation of serum levels and gene expression of tumor necrosis factor-α-induced protein-8 like-2 with Parkinson disease severity.

Different immune-mediated mechanisms involved in the pathogenesis of Parkinson disease (PD) as a neurodegenerative and inflammatory disease. According to our knowledge, there is no report evaluating Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2), a cytokine maintaining immune homeostasis, in PD. We analyzed the correlation of the serum levels and circulatory gene expression of TIPE2 with severity of PD. In this case-control study, 43 patients with PD and 40 healthy subjects were enrolled. The diagnosis of PD was performed byclinical diagnostic criteria of the UK Parkinson's Disease Society Brain Bank. The severity of PD was evaluated by modified Hoehn and Yahr (H and Y) scale. Serum levels and gene expression of TIPE2 were assessed by Elisa and real time PCR, respectively. The mean serum levels and gene expression of TIPE2 in patients with PD did not have significant difference compared to healthy subjects. Linear multiple regression analysis showed that increased serum levels of TIPE2 are positively related to age and severity of PD (P ≤ 0.0001). In addition, the gene expression of TIPE2 was found to be associated with age (P < 0.0001). Our study showed that the serum levels of TIPE2 and its gene expression might be important prognostic biomarkers of PD.

Serological and molecular survey of toxoplasmosis in renal transplant recipients and hemodialysis patients in Kashan and Qom regions, central Iran.

Toxoplasma gondii is one of the important opportunistic pathogen among solid-organ transplant recipients and hemodialysis patients (HD). This study was aimed to detect toxoplasmosis among 50 renal transplant recipients (RTR), 135 HD and 120 healthy individuals in two cities (Kashan and Qom) that located in the center of Iran, from 2014 to 2015. Serological detection (IgG and IgM antibodies) was performed among all individuals in case and control groups. Molecular detection was performed on all IgM positive individuals or IgG positive with moderate to high (>51 IU/mL) antibody titers in HD (n = 42) and control groups (n = 21). In RTR patients, molecular detection was conducted among all seropositive or seronegative individuals (n = 50). IgG seropositivity was detected in 52% (26/50) of RTR, 63% (85/135) of HD and 33.3% (40/120) of the control group. The rate of anti-T. gondii IgG antibody was significantly elevated in RTR and HD patients than the control group (p = 0.023 and p < 0.001, respectively). IgM seropositivity was only detected in one HD patient. T. gondii DNA was detected in 12% (6/50) of RTR and 7.1% (3/42) of HD patients. The results of this study suggested that the screening of toxoplasmosis should be given greater consideration among RTR and hemodialysis patients.

Predicting role of Myc-induced nuclear antigen 53 in determining the development and severity of systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus (SLE) as an autoimmune disease can relate to an imbalance between regulatory T cells (Tregs) and Th17 cells. Previous reports have shown that Myc-induced nuclear antigen (Mina) 53 protein is involved in the developments of Tregs and Th17 cells. Therefore, the current study focused on determining whether Mina53 level is correlated to the severity of SLE. Methods: The blood samples were collected from 60 patients with SLE (30 cases with mild SLE and 30 cases with severe SLE) and 30 healthy subjects. The serum concentration of Mina53 was measured using enzyme-linked immunosorbent assay (ELISA). The expression of Mina53 gene was assessed using real-time PCR method after extracting RNA from isolated peripheral blood mononuclear cells and synthesizing cDNA. Results: Patients with SLE showed significant increases in the serum level and gene expression of Mina53 compared to healthy subjects (P<0.001). Furthermore, serum level and gene expression of Mina53 showed significant effects on SLE disease and its severity (P<0.01). There was the highest sensitivity and maximum specificity in the cut-off point of Mina53 serum level equal to 125.4 (area under the curve (AUC)=0.951) and Mina53 expression level equal to 8.5 (AUC=0.88) for SLE diagnosis. The cut-off point of Mina53 serum level equal to 139.5 (AUC=0.854) and the cut-off point of Mina53 expression level equal to 8.5 (AUC=0.788) had the highest sensitivity and maximum specificity determining severe forms of SLE. Discussion: Our results showed that the changes in serum and expression levels of Mina53 have significant effects on SLE disease and its severity. These levels may be considered as diagnostic and predictive markers for SLE.

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.

Oncolytic viruses: A novel treatment strategy for breast cancer.

Breast cancer, an unceasingly occurring neoplasm, is one of the major determinants of mortality in women. Several ineffective attempts have been pursued using with conventional therapies against breast cancer. Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses. Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells. Several different DNA- and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus, herpes virus, vaccinia, reovirus, Newcastle Disease virus, measles virus and vesicular stomatitis virus. This review aims to summarize the viro-therapeutical agents against breast malignancies. Key Scientific Concepts of Review: In this review paper, we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs. These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.

Correlation of Serum Levels of Interleukine-16, CCL27, Tumor Necrosis Factor-related Apoptosis-inducing Ligand, and B-cell Activating Factor with Multiple Sclerosis Severity.

The pathogenic roles of Interleukine-16 (IL-16), CCL27, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and B-cell activating factor (BAFF) has been shown in some autoimmune and inflammatory diseases. We aimed to correlate the circulatory changes of such factors with the severity of disease in patients with multiple sclerosis (MS). This case-control study was conducted on 84 MS patients and 83 healthy controls. We measured the serum levels of IL-16, CCL27, TRAIL, and BAFF in all participants by enzyme-linked immune sorbent assay. Using the expanded disability status scale (EDSS), we evaluated the severity of MS. Finally, we assessed the correlation between serum levels of such factors with the severity of MS. We found increased serum levels of CCL27, IL-16, and BAFF in patients with MS compared to those in healthy subjects. However, no difference was found in serum levels of TRAIL between the patients and controls. In addition, a significant positive correlation between serum levels of CCL27, IL-16, TRAIL, and BAFF with disease severity according to EDSS score was determined. We showed higher serum levels of CCL27, BAFF, TRAIL, and IL-16 in MS patients with more severe disabilities than mild forms. Such finding may represent their contribution to the pathogenesis of MS. Blocking such molecules may yield new treatments for MS.

The relationship between T-cell infiltration in biopsy proven acute T-cell mediated rejection with allograft function and response to therapy: A retrospective study.

AIM: To evaluate the degree of CD3, CD20, Th17, and Tregs infiltration in kidney biopsy of the patients with acute cellular rejection and the possible relation with graft outcome. MATERIALS AND METHODS: In this retrospective study, fifty patients with Acute T Cell-Mediated Rejection (ATCMR) were enrolled. Previous and one year clinical follow-up data were collected. The kidney specimens were evaluated for infiltration of CD3, CD20, FOXP3, and Th17 with IHC. According to the serum creatinine level in one-year follow-up of the patients after rejection therapy and function of the transplanted organ from the day admitted into the hospital, they were respectively categorized in Stable graft function versus impaired graft function; appropriate response to treatment versus failure to response. RESULTS: Treg (P = 0.96) and Th17 (P = 0.24) cells were more in the unstable group than the stable group, but the difference wasn't significant. On the other hand, the FOXP3/Th17 ratio was higher in the stable group (P = 0.22). Moreover Treg (P = 0.1) and Th17 (P = 0.15) were higher in failure to response group, but FOXP3/Th17 was higher in proper response group (P = 0.8). CONCLUSION: From the results, it can be concluded that TH17 infiltration has a more significant effect on graft outcome and response to rejection therapy.

Investigating the Correlation between Growth Differentiation Factor 15 Serum Level and Its Gene Expression with Psoriasis and Its Severity.

Psoriasis is a chronic inflammatory dermatitis characterized by an inflammatory epidermal hyperproliferation. Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-ß family, has immune modulatory roles in autoimmune condition of Psoriasis. This study aimed to evaluate the relationship between GDF-15 serum levels as well as gene expression with psoriasis and its severity. This case-control study was performed on 45 patients with psoriasis Vulgaris and 45 healthy individuals. The severity of the disease was determined based on the psoriasis area and severity index (PASI score). Serum levels of GDF-15 were measured by enzyme-linked immunosorbent assay (ELISA) and its gene expression in peripheral blood mononuclear cells was quantified by real-time polymerase chain reaction (RT-PCR). The mean serum levels of GDF-15 in patients and controls were 1.98±1.57 ng/mL and 0.93±0.48 ng/mL, respectively. GDF-15 gene expression was measured as 9.7±6.6% in the patient group and 7.6±2.5% in the healthy group. The mean of GDF-15 serum levels in mild, moderate, and severe cases of psoriasis were 0.45±0.35, 2.27±0.7, and 3.5±1.6 ng/mL, respectively, indicating that elevated serum levels of GDF-15 correlate significantly with disease severity. The mean of GDF-15 gene expression in the mild, moderate, and severe forms of psoriasis were 5.25±3.2, 7.6±2.8, and 17.8±5.7, respectively which indicate a significant relationship between GDF-15 gene expression and psoriasis severity. Based on this study, in psoriatic patients, GDF-15 serum levels and gene expression are significantly higher than those in healthy controls. Such values were correlated with disease activity, especially in severe cases. Therefore, GDF-15 may be used as a prognostic marker of psoriasis.

Serum Levels of Growth Differentiation Factor-15 as an Inflammatory Marker in Patients with Unstable Angina Pectoris.

Background: Growth differentiation factor-15 (GDF-15), a member of transforming growth factors, is a stress-responsive marker whose levels may significantly increase in response to pathological stresses associated with inflammatory tissue injuries such as unstable angina pectoris (USAP). This study evaluated the diagnostic value of GDF-15 in patients with USAP. Methods: The present cross-sectional study recruited 39 patients with USAP criteria and 30 patients with stable angina pectoris (SAP), referred to Shahid Beheshti Hospital, Kashan, Iran. All the patients with USAP had at least 1 coronary artery stenosis (>50%) in angiography. The control group comprised 42 healthy individuals. The serum levels of GDF-15 were measured in all the participants by ELISA. Also analyzed were the relationship between GDF-15 levels and thrombolysis in myocardial infarction (TIMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores in the patients with USAP to determine the severity of the disease. Result: The study population consisted of 111 subjects, 62 women and 49 men, divided into 3 groups of USAP (n=39, mean age=60.07±14.10 y), SAP (n=30, mean age=67.56±9.88 y), and control (n=42, mean age=61.21±7.76 y). The mean serum level of GDF-15 in the USAP group was significantly different from the other 2 groups (P<0.001), while no significant difference was observed in this regard between the SAP and control groups (P=0.797). No correlation was found between the mean GDF-15 serum level and the GRACE (P=0.816) and TIMI (P=0.359) risk scores in the USAP group. Conclusion: The mean serum level of GDF-15 exhibited a rise in our patients with USAP. GDF-15 may be a diagnostic biomarker of USAP and its severity.

The Relationship between Serum and Gene Expression Levels of RANK, RANKL and Osteoprotegerin Inflammatory Pathway with Unstable Angina: A Case-control Study.

 Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity.

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.

Gamma-radiated immunosuppressed tumor xenograft mice can be a new ideal model in cancer research.

Tumor xenograft models can create a high capacity to study human tumors and discover efficient therapeutic approaches. Here, we aimed to develop the gamma-radiated immunosuppressed (GIS) mice as a new kind of tumor xenograft model for biomedical studies. First, 144 mice were divided into the control and treated groups exposed by a medical Cobalt-60 apparatus in 3, 4, and 5 Gy based on the system outputs. Then, 144 BALB/c mice were divided into four groups; healthy, xenograft, radiation, and radiation + xenograft groups. The animals in the xenograft and radiation + xenograft groups have subcutaneously received 3 × 106 MCF-7 cells 24 h post-radiation. On 3, 7, 14, and 21 days after cell injection, the animals were sacrificed. Then, the blood samples and the spleen and tumor tissues were removed for the cellular and molecular analyses. The whole-body gamma radiation had a high immunosuppressive effect on the BALB/c mice from 1 to 21 days post-radiation. The macroscopic and histopathological observations have proved that the created clusters' tumor structure resulted in the xenograft breast tumor. There was a significant increase in tumor size after cell injection until the end of the study. Except for Treg, the spleen level of CD4, CD8, CD19, and Ly6G was significantly decreased in Xen + Rad compared to the Xen alone group on 3 and 7 days. Unlike IL-4 and IL-10, the spleen level of TGF-ß, INF-γ, IL-12, and IL-17 was considerably decreased in the Xen + Rad than the Xen alone group on 3 and 7 days. The spleen expressions of the VEGF, Ki67, and Bax/Bcl-2 ratio were dramatically increased in the Xen + Rad group compared to the Xen alone on 3, 7, 14, and 21 days. Our results could confirm a new tumor xenograft model via an efficient immune-suppressive potential of the whole-body gamma radiation in mice.

Ozone therapy for the treatment of COVID-19 pneumonia: A scoping review.

Severe forms of COVID-19 can evolve into pneumonia, featured by acute respiratory failure due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In viral diseases, the replication of viruses is seemingly stimulated by an imbalance between pro-oxidant and antioxidant activity as well as by the deprivation of antioxidant mechanisms. In COVID-19 pneumonia, oxidative stress also appears to be highly detrimental to lung tissues. Although inhaling ozone (O3) gas has been shown to be toxic to the lungs, recent evidence suggests that its administration via appropriate routes and at small doses can paradoxically induce an adaptive reaction capable of decreasing the endogenous oxidative stress. Ozone therapy is recommended to counter the disruptive effects of severe COVID-19 on lung tissues, especially if administered in early stages of the disease, thereby preventing the progression to ARDS.

Investigating the Relationship between Serum Levels of Interleukin-22 and Interleukin-1 Beta with Febrile Seizure.

A febrile seizure is the most common type of seizure in young kids, which is not fully known. Inflammatory mediators can affect the pathogenesis of the disease. Considering the controversy about the impacts of interleukin 1 beta (IL-1ß) and the lack of a study on interleukin 22 (IL-22), the purpose of the present study was to investigate the relationship between IL-22 and IL-1ß serum levels with febrile seizure in young kids. Our case-control study has been conducted on 120 young kids aged 6-60 months with the sign of the fever. Rectal temperature was measured for allcases. Patients with febrile seizure (n=60) and patients with fever and without a seizure (n=60) were investigated as case and control groups, respectively. Serum levels of IL-22 and IL-1ß were measured in all participants through the ELISA method. The serum level of IL-1ß was significantly higher in the case group compared to the control group (p˂0.001), while there were no significant differences between the two groups in terms of IL-22 (p=0.92). Unlike IL-1ß (p≤0.021), IL-22 showed no difference between two groups according to some demographic and clinical features like gender, age group, family history of febrile seizure, family history of epilepsy, and evolutionary status (p>0.22). Logistic multiple regression analysis showed that, unlike IL-1ß (p˂0.001), IL-22 does not change the chance of febrile seizure in the study groups (p=0.737). The findings of this study indicated that, unlike IL-1ß, IL-22 has not any changes/effects in the febrile seizure.

The correlation of helios and neuropilin-1 frequencies with parkinson disease severity.

OBJECTIVES: Parkinson disease (PD), a neurodegenerative disease, has also some immunologic basis in which several regulatory factors, like Helios and Neuropilin-1 (NRP-1) may show some roles in its pathogenesis. We aimed to evaluate the circulatory frequency of T regulatory cells (Tregs) expressing Helios and NRP-1 in PD. PATIENTS AND METHODS: In this case-control study, 83 patients with PD and 83 healthy controls were enrolled. The diagnosis of PD was accomplished in accordance with clinical diagnostic criteria of the UK Parkinson Disease Society Brain Bank. The modified Hoehn and Yahr (H and Y) were used to measure the severity of PD. Flow cytometry was used to evaluate the circulatory frequency of CD4+CD25+Foxp3+Tregs expressing and Helios and NRP-1 in all participants. Also, correlation of H and Y with such frequencies was evaluated. RESULTS: Our findings showed that frequency of CD4+CD25+Foxp3+Tregs expressing NRP-1 (P = 0.04) and Helios (P = 0.01) in patients with PD was significantly higher than those in healthy subjects. The frequency of Tregs expressing Helios and NRP-1 showed a negative correlation with H and Y criteria and disease duration. Multiple linear regression analysis indicated that the severity of PD is the only effective factor on the frequency of CD4+CD25+Foxp3+NRP-1+Tregs (P = 0.012) and CD4+CD25+FoxP3+ Helios + Tregs (P = 0.038). CONCLUSION: Our study showed that the increased frequency of Tregs expressing Helios and NRP-1 is associated with the severity of PD.

Reduced CD4+ CD25++ CD45RA- Foxp3hi activated regulatory T cells and its association with acute rejection in patients with kidney transplantation.

BACKGROUND: It was found that regulatory T cells (Tregs) importantly affect the maintenance of the kidney graft. However, Tregs are a heterogeneous population with less to more suppressive activity. The aim of this study was to determine the effects of different subsets of Tregs, as well as their ratio to effector T cells (Teff), on kidney transplantation outcomes. METHODS: A total of 58 participants were enrolled in this study and divided into four groups: (i) first kidney transplant recipients (stable 1); (ii) second kidney transplant recipients (stable 2); (iii) transplant recipients with acute rejection (AR); and (iv) healthy control subjects. By using flow cytometer, the frequencies of CD4+ CD25++ CD45RA- Foxp3hi activated Tregs (aTregs), CD4+ CD25+ CD45RA+ Foxp3lo resting Tregs (rTregs), CD4+ CD25+ CD45RA- Foxp3lo non-suppressive T cells, CD4+ CD25+ Foxp3- cells Teff, and total Tregs were analyzed in all subjects. RESULTS: The frequency of aTregs (as well as the ratio of aTregs/Tregs) was significantly lower in the AR patients than the other three groups. In contrast to AR patients, stables 1 and 2 had a higher aTreg/Treg ratio than those in the control group. Although patients with AR had a significantly lower total Tregs than the other three groups, the balance of total Tregs and Teff was similar between patients with and without AR. CONCLUSION: Patients with AR had poorer immunoregulatory properties than those with normal graft functioning, as well as those in the control group. These reduced immunoregulatory properties in patients with AR could lead to graft rejection.

Evaluating Serum Levels of Pentraxin-3, von Willebrand Factor and C-X-C Motif Chemokine Ligand 13 as Inflammatory Markers of Unstable Angina Pectoris.

Unstable angina pectoris (USAP) is a complex condition in which widespread coronary inflammatory processes have important implications for clearer understanding of its pathogenesis and also its treatment. This study aimed at evaluating the diagnostic as well as prognostic value of serum inflammatory markers of pentraxin-3 (PTX-3), Von Willebrand Factor (vWf) and C-X-C Motif Chemokine Ligand 13 (CXCL13) in such patients. Out of sixty-nine patients, thirty-nine had USAP, thirty had stable angina pectoris (SAP), and thirty-nine were healthy controls. For all participants, serum PTX-3, vWf and CXCL13 levels were measured using ELISA. For each patient with USAP, the Thrombolysis in Myocardial Infarction (TIMI) and the scores of Global Registry of Acute Coronary Events (GRACE) were calculated to determine the severity of the disease. We, then, analyzed the relation of PTX-3, vWf and CXCL13 levels with TIMI and GRACE scores in patients with USAP. Serum PTX-3, vWf and CXCL13 levels were significantly higher in USAP group than those in either SAP or control groups (p˂0.001). Strong correlation was observed between CXCL13 level and TIMI risk score (p=0.019). In receiver operating characteristic (ROC) curves, area under the curve (AUC) values of PTX3, vWf and CXCL13 for detection of USAP were 0.755, 0.751, and 0.906, respectively. The levels of serum PTX3, vWf and CXCL13 increased in patients with USAP. The notable correlation implied that CXCL13 might be a sensitive and specific biomarker for the diagnosis of USAP as well as its severity. It might also show additional diagnostic values when measured in combination with vWf.

The Study of Relationship between Serum Levels of Soluble fms-like Tyrosine Kinase-1 and Soluble Fibrinogen-like Protein 2 with Delayed Graft Function after Kidney Transplantation.

Delayed graft function (DGF) is a transplant complication which means a need to dialysis throughout the first week after transplantation. This study aimed to ascertain the relationship between the two immunomodulatory factors of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble fibrinogen-like protein 2 (sFGL-2) with DGF after transplantation. This case-control study was done in 2 groups of 58 kidney transplant patients with and without DGF. The control group included the patients who didn't show DGF symptoms. Then, serum levels of sFlt-1and sFGL-2 in all blood samples were measured by ELISA. Serum sFlt-1 and sFGL-2 levels were significantly higher in the DGF group compared to those in the control group (p≤0.001). sFlt-1 and sFGL-2 serum levels significantly affect DGF (p<0.001) in such a way that they may be diagnostic factors of DGF. This study showed a significant relationship between sFlt-1 as well as sFGL-2 and DGF. Therefore, plasma levels of sFlt-1 and sFGL-2 may be used as diagnostic tools to determine the risk of DGF.

Monitoring cellular immune function of renal transplant recipients based on adenosine triphosphate (ATP) production by mitogen-induced CD4+ T helper cells.

Maintaining the balance between over- and under-immunosuppression has a critical role for successful immunosuppressive therapy after renal transplantation. We studied the predictive value of our functional immune assay, which works based on adenosine triphosphate (ATP) levels, in determining risk of infection and rejection among renal transplant recipients (RTRs). A total of 65 RTRs with less than 1 month (RTRL1) and 48 RTRs with more than 6 months (RTRM6) of post-transplant time, and 56 healthy individuals were included. Upon lymphocyte activation by phytohemagglutinin (PHA), CD4+ T cells were separated using magnetic beads (Dynabeads), the intracellular ATP (iATP) concentrations were measured by luciferin-luciferase reaction, and compared within and between the groups. Activated CD4+ cells iATP production directly correlated with post-transplant time (r = 0.32, P = 0.011). The iATP levels were significantly lower in both RTRL1 and RTRM6 groups compared to control (P < 0.001), and in the RTRL1 group compared to the RTRM6 (P < 0.05). The iATP concentrations were significantly lower in patients who suffered from infection versus the RTRs with stable graft function (SGF). However, the iATP levels were higher in those with allograft rejection episode (ARE). Our optimization experiments showed that best iATP levels cutoffs were 472.5 and 572.5 ng/ml for predicting risk of ARE, and 218.5 and 300.5 ng/ml for predicting risk of developing infection in RTRL1 and RTRM6 patients, respectively. iATP levels measured by immune function assay might be a promising predictive tool for identifying RTRs who are at risk of developing infection or allograft rejection.