Impact of BK Polyomavirus NCCR variations in post kidney transplant outcomes.

The human BK Polyomavirus (BKPyV) is a DNA virus that is prevalent in 80 % of the population. Infection with this virus may begin in childhood, followed by asymptomatic persistence in the urinary tract. However, in immunocompromised individuals, especially kidney transplant recipients (KTRs), heightened replication of BKPyV can lead to severe complications. The genome of this virus is divided into three parts; the early and late region, and the non-coding control region (NCCR). Mutations in the NCCR can change the archetype strain to the rearranged strain, and NCCR rearrangements play a significant in virus pathogenesis. Interestingly, diverse types of NCCR block rearrangement result in significant differences in conversion potential and host cell viability in the infected cells. A correlation has been detected between increased viral replication potential and pathogenesis in BKPyV-infected KTRs with specific NCCR rearrangements. The objective of this review study was to examine the disease-causing and clinical consequences of variations in the NCCR in BKPyV-infected KTRs such as virus-associated nephropathy (BKPyVAN).

Regulatory role of T helper 9/interleukin-9: Transplantation view.

T helper 9 (Th9) cells, a subset of CD4+ T helper cells, have emerged as a valuable target for immune cell therapy due to their potential to induce immunomodulation and tolerance. The Th9 cells mainly produce interleukin (IL)-9 and are known for their defensive effects against helminth infections, allergic and autoimmune responses, and tumor suppression. This paper explores the mechanisms involved in the generation and differentiation of Th9 cells, including the cytokines responsible for their polarization and stabilization, the transcription factors necessary for their differentiation, as well as the role of Th9 cells in inflammatory and autoimmune diseases, allergic reactions, and cancer immunotherapies. Recent research has shown that the differentiation of Th9 cells is coregulated by the transcription factors transforming growth factor ß (TGF-ß), IL-4, and PU.1, which are also known to secrete IL-10 and IL-21. Multiple cell types, such as T and B cells, mast cells, and airway epithelial cells, are influenced by IL-9 due to its pleiotropic effects.

Sequence Analysis of Hot Spot Regions of Spike and RNA-dependent-RNA polymerase (RdRp) Genes of SARS-CoV-2 in Kerman, Iran.

Background: Mutations in the SARS-CoV-2 genome might influence pathogenicity, transmission rate, and evasion of the host immune system. Therefore, the purpose of the present study was to investigate the genetic alteration as well as assess their effects on the receptor binding domain (RBD) of the spike and the putative RNA binding site of the RdRp genes of SARS-CoV-2 using bioinformatics tools. Materials and Method: In this cross-sectional study, 45 confirmed COVID-19 patients using qRT-PCR were included and divided into mild, severe, and critical groups based on the severity of the disease. RNA was extracted from nasopharyngeal swab samples using a commercial kit. RT-PCR was performed to amplify the target sequences of the spike and RdRp genes and sequence them by the Sanger method. Clustal OMEGA, MEGA 11 software, I-mutant tools, SWISS-MODEL, and HDOCK web servers were used for bioinformatics analyses. Results: The mean age of the patients was 50.68±2.73. The results showed that four of six mutations (L452R, T478K, N501Y, and D614G) in RBD and three of eight in the putative RNA binding site (P314L, E1084D, V1883T) were missense. In the putative RNA binding site, another deletion was discovered. Among missense mutations, N501Y and V1883T were responsible for increasing structural stability, while others were responsible for decreasing it. The various homology models designed showed that these homologies were like the Wuhan model. The molecular docking analysis revealed that the T478K mutation in RBD had the highest binding affinity. In addition, 35 RBD samples (89.7%) and 33 putative RNA binding site samples (84.6%) were similar to the Delta variant. Conclusion: Our results indicated that double mutations (T478K and N501Y) in the S protein might increase the binding affinity of SARS-CoV-2 to human ACE2 compared to the wild-type (WT) strain. Moreover, variations in the spike and RdRp genes might influence the stability of encoded proteins.

The effect of the BK polyomavirus large T antigen on the function and maturity of the CD4+ T cell subsets in kidney transplant recipients.

BACKGROUND: In kidney transplant recipients (KTRs) who are immunosuppressed, human BK polyomavirus (BKPyV) infection can be reactivated, resulting in BKPyV-associated nephropathy (BKPyVN). Considering that BKPyV inhibits CD4+ T cell differentiation, we investigated the effect of BKPyV large T antigen (LT-Ag) on the maturation of CD4+ T cell subsets during active BKPyV infection. METHODS: In this cross-sectional study, we examined the following groups: 1) five KTRs with active viral infection (BKPyV+ KTRs), 2) five KTRs without active viral infection (BKPyV-KTRs), and 3) five healthy controls. We measured the frequency of CD4+ T cells and their different subsets, such as naive T cells, central memory T cells (Tcm), and effector memory T cells (Tem). All these subsets were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs) stimulated with the overlapping BKPyV LT-Ag peptide pool. In addition, CD4+ T cell subsets were analyzed by flow cytometry for the presence of CD4, CCR7, CD45RO, CD107a, and granzyme B (GB). In addition, mRNA expression of transcription factors (TFs) such as T-bet, GATA-3, STAT-3, and STAT-6 was examined. The probability of inflammation with perforin protein was examined by SYBR Green real-time PCR. RESULTS: After stimulation of PBMCs, naive T cells (CD4+CCR7+CD45RO-) (p = 0.9) and CD4+ T cells which release CD107a+ (CD4+CD107a+Geranzyme B-) (p = 0.9) T cells were more abundant in BKPyV+ KTRs than in BKPyV- KTRs. In contrast, central memory T cells (CD4+CCR7+CD45RO+) (p = 0.1) and effector memory T cells (CD4+CCR7-CD45RO+) (p = 0.1) were more abundant in BKPyV- KTRs than in BKPyV+ KTRs. The mRNA expression levels of T-bet, GATA-3, STAT-3, and STAT-6 were significantly higher (p < 0.05) in BKPyV- KTRs than in BKPyV+ KTRs which may be due to a higher differentiation level of CD4+ T cells. Due to inflammation, the mRNA expression level of perforin was higher in BKPyV+ KTRs, than in BKPyV- KTRs, but the difference was not significant (p = 0.175). CONCLUSIONS: The high number of naive T cells after PBMC stimulation with the LT-Ag peptide pool was observed in BKPyV+ KTRs due to the interaction of LT-Ag with T cells. This means that BKPyV by using its LT-Ag can inhibit the naive T cell differentiation to other T cell subsets like central and effector memory T cells. However, the frequency of CD4+ T cell subsets and the combination of the activities of these cells with the expression profile of the target genes in this study may be efficient in treating and diagnosing BKPyV infections in kidney recipients.

Decreased frequency of Th22 cells and IL-22 cytokine in kidney transplant patients with active cytomegalovirus infection.

BACKGROUND: The immunity of CD4+ T cell subsets against human cytomegalovirus (HCMV) is considerable due to their essential role in controlling the infection in transplant individuals. Previously explained CD4+ subsets such as T helper (Th) 1 have been proven to have a protective role against HCMV infection, while the role of the recently identified Th22 subset has not been described yet. Here, the frequency changes of Th22 cells and the IL-22 cytokine production were investigated in kidney transplant recipients with and without HCMV infection. METHODS: Twenty kidney transplant patients and ten healthy controls were enrolled in this study. Patients were categorized into HCMV + and HCMV- groups based on the HCMV DNA real-time PCR results. After isolating CD4+ T cells from PBMCs, the phenotype (CCR6+CCR4+CCR10+) and cytokine profile (IFN-γ-IL-17-IL-22+) of Th22 cells were analyzed by flow cytometry. The gene expression of Aryl Hydrocarbon Receptor (AHR) transcription factor was analyzed by real-time PCR. RESULTS: The phenotype frequency of these cells was lower in recipients with infection than in those without infection and healthy controls (1.88 ± 0.51 vs. 4.31 ± 1.05; P = 0.03 and 4.22 ± 0.72; P = 0.01, respectively). A lower Th22 cytokine profile was observed in patients with infection than in the two other groups (0.18 ± 0.03 vs. 0.20 ± 0.03; P = 0.96 and 0.33 ± 0.05; P = 0.04, respectively). AHR expression was also lower in patients with active infection. CONCLUSIONS: Overall, this study for the first time suggests that the reduced levels of Th22 subset and IL-22 cytokine in patients with active HCMV infection might indicate the protective role of these cells against HCMV.

The relation of NCCR variations and host transcription factors gene regulation in BK polyomavirus infected kidney transplant patients.

BACKGROUND: BK polyomavirus (BKPyV) infection in immunocompromised patients can led to polyomavirus-associated nephropathy (BKPyVAN) especially after kidney transplantation. The polyomavirus genome contains enhancer elements that are important transcription activators. In this study, the association between viral and host gene expression and NCCR variations was evaluated in kidney transplant recipients (KTRs) with BKPyV active, and BKPyV in-active infection. METHODS AND RESULTS: Blood samples were collected from selected KTRs who divided to patients with active and in-active BKPyV infection. Transcriptional control region (TCR) anatomy was compared to the genomic sequence of archetype BKPyV strain WW using nested PCR method and sequencing. The expression level of some transcription factor genes was evaluated using in-house Real-time PCR (SYBR Green) technique. Most changes were observed after TCR anatomy detection in the Q and P blocks. The expression level of VP1 and LT-Ag viral genes were significantly higher in patients with active infection compared with non-infected ones. Transcription factor genes SP1, NF1, SMAD, NFκB, P53, PEA3, ETS1, AP2, NFAT and AP1 were significantly higher in BKPyV active group in comparison in-active and control groups. The analyses revealed that viral load level and mutations frequency has significant correlation. CONCLUSIONS: Based on the results, increasing of NCCR variations were associated with higher viral load of BKPyV especially in Q block. Host transcriptional factors and viral genes all had higher express level in active BKPyV patients versus no in-active ones. Detection of the relation between NCCR variation and BKPyV severity in KTRs need to be confirmed in further complicated studies.

Are the Costimulatory Molecule Gene Polymorphisms (CTLA-4) Associated With Infection in Organ Transplantation? A Meta-Analysis.

Organ transplantation has been linked to certain gene polymorphisms. The effect of gene polymorphisms-associated organ transplantation gene on infection, on the other hand, is yet unknown. The research studying the link between the CTLA-4 rs5742909, rs733618, rs4553808, rs231775, and polymorphisms of the organ transplantation gene and infection were found in PubMed, Web of Science, Scopus, and Embase, and the published articles from 2012 to 2020 were gathered. For the best estimation of the intended results, a random-effects model was used in this meta-analysis. In this study, 1,567 studies were initially included and 9 eligible studies were eligible for further analyses. A significant correlation between CTLA4+49 [A/G-231775 odds ratio (OR) = 077, 0.59-0.95] and CTLA4 [rs5742909TT OR: 0.09, 0.27-0.45] gene polymorphism with infection in organ transplantation was observed. Also, no significant association was found between other CTLA4 gene polymorphisms with infection in organ transplantation. Further studies involving gene-gene and gene-diet interactions should be conducted to investigate this association with infection.

Host and viral RNA dysregulation during BK polyomavirus infection in kidney transplant recipients.

Early detection of BK polyomavirus (BKPyV) infection in kidney transplant recipients (KTRs) would enhance their quality of life and save the allograft. Still, many patients lose their grafted kidneys because of this infection. BKPyV microRNAs (miRNAs) have been detected in KTRs during viral infection. BKPyV produces two mature miRNAs that are named BKV-miR-B1-5p and BKV-miR-B1-3p. Additionally, BKPyV associated nephropathy (BKVAN) in kidney transplanted patients cause changes in the expression level of host genes and miRNAs such as IFN-É£, BCLA2A1, has-miR-10, and has-miR-30a. BKVAN can alter viral genes and miRNAs expression level, too, like viral miRNAs and T-Ag. However, their potential value as viral infection markers and the regulatory network produced by their expression during viral-host interactions needs more consideration since there are no approved medications for treating BKPyV-related diseases in KTRs. Hence, it is vital to recognize complicated facts regarding the impact of BKPyV infection on the distribution of miRNAs and mRNAs within the host cell and the virus. This article is categorized under: Translation > Regulation RNA Processing > Processing of Small RNAs RNA in Disease and Development > RNA in Disease.

Study the mRNA level of IL-27/IL-27R pathway molecules in kidney transplant rejection.

BACKGROUND: Renal transplantation stands as the sole remedy for individuals afflicted with end-stage renal diseases, and safeguarding them from transplant rejection represents a vital, life-preserving endeavor posttransplantation. In this context, the impact of cytokines, notably IL-27, assumes a critical role in managing immune responses aimed at countering rejection. Consequently, this investigation endeavors to explore the precise function of IL-27 and its associated cytokines in the context of kidney transplant rejection. METHODS: The study involved the acquisition of blood samples from a cohort of participants, consisting of 61 individuals who had undergone kidney transplantation (comprising 32 nonrejected patients and 29 rejected patients), and 33 healthy controls. The expression levels of specific genes were examined using SYBR Green Real-time PCR. Additionally, the evaluation encompassed the estimation of the ROC curve, the assessment of the relationship between certain blood factors, and the construction of protein-protein interaction networks for the genes under investigation. RESULTS: Significant statistical differences in gene expression levels were observed between the rejected group and healthy controls, encompassing all the genes examined, except for TLR3 and TLR4 genes. Moreover, the analysis of the Area Under the Curve (AUC) revealed that IL-27, IL-27R, TNF-α, and TLR4 exhibited greater significance in discriminating between the two patient groups. These findings highlight the potential importance of IL-27, IL-27R, TNF-α, and TLR4 as key factors for distinguishing between individuals in the rejected group and those in the healthy control group. CONCLUSIONS: In the context of kidney rejections occurring within the specific timeframe of 2 weeks to 2 months post-transplantation, it is crucial to emphasize the significance of cytokines mRNA level, including IL-27, IL-27R, TNF-α, and TLR4, in elucidating and discerning the diverse immune system responses. The comprehensive examination of these cytokines' mRNA level assumes considerable importance in understanding the intricate mechanisms underlying kidney rejection processes during this critical period.

Cohort Profile: Shiraz Pediatric Liver Cirrhosis Cohort (SPLCCS).

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort's features, the included population's baseline characteristics, and primary outcomes are reported.

The Impact of HLA-G and HLA-E Polymorphisms on CMV Reinfection in Liver Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) reinfection in transplant patients has been associated with graft loss and decreased patient survival. In this regard, the HLA-G molecule has the immunomodulatory characteristic and its soluble isoforms have important roles in immunity to viruses. The 14bp insertion/deletion polymorphism impacts HLA-G mRNA stability. Regarding the HLA-E molecule, two nonsynonymous alleles, HLA-E*0101, and HLA-E*0103 are different in their functions including the affinity of the relative peptide. OBJECTIVE: To explore the possible link between HLA-G and HLA-E polymorphisms with CMV reinfection among liver transplant recipients (LTRs). METHODS: In this study, a total of 140 liver transplantations were performed; of which 70 CMV-reactivated LTRs and 70 CMV non-reactivated ones were recruited. The cut-off value of CMV DNA was determined to be 100 copies/mL. PCR evaluated different genotypes for HLA-G and ARMS-PCR for HLA-E*0101 and *0103. RESULTS: Neither the HLA-G genotypes (-14 bp/-14bp and +14bp/+14 bp homozygous genotypes with the p-values: 0.43, and 0.13, respectively +14 bp/-14 bp heterozygous genotype with p-value: 0.49) nor the HLA-E genotypes (HLA-E*0101/0103, HLA-E*0101/0101, and HLA-E*0103/0103 with the p-values: 0.152, 0.249, and 0.391, respectively) had any association with CMV reinfection in the LTRs. CONCLUSION: No difference was observed in the HLA-E and HLA-G genotype frequencies between our studied groups. Further studies are needed to explore other genetic variations and evaluate soluble HLA-G and HLA-E levels in the transplant population.

Association between expression of ZBP1, AIM2, and MDA5 genes and severity of COVID-19.

Antiviral and inflammatory responses following the detection of the virus genome by nucleic acid sensors play a vital role in the pathogenesis and outcome of diseases. In this study, we investigated the ZBP1, AIM2, and MDA5 expression levels in COVID-19 patients with different intensities of the disease. 75 quantitative Real-Time PCR (qRT-PCR)-confirmed COVID-19 patients were included consecutively and divided into 3 groups of mild, severe, and critical based on the severity of the disease. Also, 25 healthy volunteer subjects were included. PBMCs were collected from the whole blood, and RNA was extracted using commercial kit. The expression of ZBP1, AIM2, and MDA5 genes was investigated using qRT-PCR technique. The mean age of the patients and healthy volunteers was 52.73±13.78 and 49.120±12.490, respectively. In each group, 13 out of 25 participants were male. The expression levels of ZBP1 (P=0.001), AIM2 (P=0.001), and MDA5 (P= 0.003) transcript were significantly higher in COVID-19 patients than the control group. The results also revealed that the expression levels of ZBP1, AIM2, and MDA5 were significantly higher in the critical and severe COVID-19 patients compared to those with mild disease (P<0.05). Moreover, regarding the gender, the expression levels of AIM2 and MDA5 were significantly elevated in male severe (P=0.04 and P=0.003, respectively) and critical (P=0.005 and P=0.0004, respectively) patients than the female ones. The results indicated that ZBP1, AIM2, and MDA5 genes might have an important role in the severity of COVID-19 disease. Moreover, the severity of COVID-19 disease in male and female patients might be related to AIM2, and MDA5 expression levels. More studies are recommended to be conducted to clarify this issue.

Altered Signatures of Plasma Inflammatory Proteins and Phonotypic Markers of NK Cells in Kidney Transplant Patients upon CMV Reactivation.

Cytomegalovirus (CMV) reactivation remains a common opportunistic infection with a prominent role in immune reconstitution in organ transplant recipients. CMVs as important drivers of natural killer (NK) cell differentiation has been indicated to prompt several phenotypic and functional alteration in these cells. We aimed to monitor the reconstitution of NK cells and change the signature of inflammatory proteins at the critical phase of CMV reactivation over six months after kidney transplantation. The present study indicated that CMV reactivation is associated with the development of IL-6, IL-10, and cytotoxic granules, including granzyme-B and granulysin, and the drop in the frequency of CD16 + NKG2A-CD57 + NK cell subset in kidney transplant recipients (KTRs) with reactivation versus non- reactivated ones. Our findings describe distinct immune signatures that emerged with CMV reactivation after kidney transplantation, which may be helpful in the timely management of CMV infection in KTRs.

Cytomegalovirus microRNAs level determination in kidney recipients post transplantation.

BACKGROUND: Human cytomegalovirus (CMV) can establish a latent infection with periodic or sporadic reactivation after the first infection happens. Primary and recurrent infection, results in different problems in patients with impaired or immature immune systems, such as kidney transplant recipients (KTRs). MicroRNAs (miRNAs, miRs) are important regulatory molecules in the outcome of CMV-infected KTRs. Therefore, in this study the expression level of CMV miRNAs were evaluated in active vs. latent CMV infected KTRs. METHODS: Expression of viral miRNAs were studied in 61 KTRs which were divided into 30 active CMV and 31 latent CMV infected individuals. In order to study the expression level of selected miRNAs, SYBR Green Real-time PCR technique was exploited. Also, mature miRNAs expression level that were produced from one precursor, studied both in active and latent situations. RESULTS: Among studied miRNAs' expression level, CMV miR-UL112-3p/5p, -UL22A-3p/5p, -US25-1-5p, -US25-2-3p/5p, -UL36-3p/5p and -UL70-3p showed significant increase in active CMV infected KTRs in comparison to latent ones. The ROC curve analysis results for miR-UL112-3p, -UL22A-3p, -US25-2-3p, -UL36-3p and -UL70-3p showed significant difference between two studied patient groups. CONCLUSION: This study revealed an extremely high expression level in CMV miR-UL112-3p/5p, -UL22A-3p/5p, -US25-1-5p, -US25-2-3p/5p, -UL36-3p/5p and -UL70-3p in active CMV infected KTRs in comparison to latent ones. Further studies might help in finding the capability of miRNAs to differentiate active from latent stage of CMV infection in KTRs.

Optimization of 3D islet-like cluster derived from human pluripotent stem cells: An efficient in vitro differentiation protocol.

Development of an optimized protocol to produce sufficient functional human insulin-producing islet-like cluster is important as a potential therapeutic strategy for diabetes as well as in vitro studies. Here, we described a stepwise protocol for differentiation of the human induced pluripotent stem cell line (R1-hiPSC1) into the islet-like cluster using several growth factors and small molecules. Therefore, various differentiation steps have been adopted to maximize mimicking of developmental processes in order to form functional islet like cluster. The differentiation protocol enables us to generate 3D islet-like clusters with highly viable cells, which are insulin producer and glucose responsive. Transcriptome analysis of transcription factors and functional genes revealed high coordination between gene expressions and resembling to those reported during natural development of islet cell. This coordination was further confirmed by hierarchical clustering of genes during differentiation. Furthermore, the islet-like clusters were enriched with insulin producing cells and formed glucose responsiveness behavior upon stimulation with glucose. Our protocol provides a robust platform and well-behaved model for additional developmental studies and shed light our clusters as a good candidate for in vitro model. Further studies are needed to assess the hormonal content of this cluster as well as transplantation into the animal model.

The effect of BK polyomavirus large T antigen on CD4 and CD8 T cells in kidney transplant recipients.

Human BK polyomavirus (BKPyV) can affect the machinery of the host cell to induce optimal viral replication or transform them into tumor cells. Reactivation of BKPyV happens due to immunosuppression therapies following renal transplantation which might result in BK polyomavirus nephropathy (BKPyVAN) and allograft loss. The first protein that expresses after entering into host cells and has an important role in pathogenicity is the Large T antigen (LT-Ag). In this review tries to study the molecular and cellular inter-regulatory counteractions especially between CD4 and CD8 T cells, and BKPyV LT-Ag may have role in nephropathy after renal transplantation.

An Update on Protective Effectiveness of Immune Responses After Recovery From COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits variable immunity responses among hosts based on symptom severity. Whether immunity in recovered individuals is effective for avoiding reinfection is poorly understood. Determination of immune memory status against SARS-CoV-2 helps identify reinfection risk and vaccine efficacy. Hence, after recovery from COVID-19, evaluation of protective effectiveness and durable immunity of prior disease could be significant. Recent reports described the dynamics of SARS-CoV-2 -specific humoral and cellular responses for more than six months in convalescent SARS-CoV-2 individuals. Given the current evidence, NK cell subpopulations, especially the memory-like NK cell subset, indicate a significant role in determining COVID-19 severity. Still, the information on the long-term NK cell immunity conferred by SARS-CoV-2 infection is scant. The evidence from vaccine clinical trials and observational studies indicates that hybrid natural/vaccine immunity to SARS-CoV-2 seems to be notably potent protection. We suggested the combination of plasma therapy from recovered donors and vaccination could be effective. This focused review aims to update the current information regarding immune correlates of COVID-19 recovery to understand better the probability of reinfection in COVID-19 infected cases that may serve as guides for ongoing vaccine strategy improvement.

Tissue presentation of human pegivirus infection in liver transplanted recipients.

Human pegivirus-1 (HPgV-1) is known for its protective role in HIV co-infected individuals. This immunomodulatory effect raised questions concerning the possible role of HPgV-1 infection and the risk of rejection in liver transplanted patients. We aimed to evaluate the possible protective effect of HPgV-1 on graft outcome of liver transplanted patients. A total of 283 patients were recruited. Formalin-fixed paraffin-embedded tissue samples were collected from the explanted liver. HBV-DNA, HCV-RNA, and HPgV-1-RNA were determined using PCR and multiplex RT-PCR assays. The clinical course of patients including the occurrence of acute cellular rejection was compared between HPgV-1-infected vs. uninfected patients. HBV-DNA, HCV-RNA and HPgV-1-RNA were detected in 42.6%, 4.9%, and 7.8% of samples, respectively. None of the HPgV-1-infected patients experienced graft rejection. Group LASSO logistic regression revealed that HPgV-1 infection was the only factor which significantly reduced the odds of graft rejection (OR = 0.5, 95% CI = 0.29-0.89). No significant association was found between the presence of HPgV-1 with HBV and HCV infections. The lack of graft rejection in HPgV-1-infected liver transplanted patients might indicate a possible role of this virus for graft surveillance. Since these are still preliminary findings, prospective studies should further elucidate the role of HPgV-1 in liver transplantation outcomes.

Loss of CCR7 Expression on CD57 + CD56/ CD16 + NK Cells Correlates with Viral Load in CMV Reactivated Kidney Transplant Recipients.

INTRODUCTION: Despite developing strategies for antiviral treatment, cytomegalovirus (CMV) infection remains one of the most common challenges in kidney transplant recipients (KTRs). The evaluation of CMV viral load is still the most practical main clinical approach for CMV assessment and guides decision-making in recipient antiviral treatment. However, there is not a specific viral load cut off for initiating treatment yet. On the other hand, the cellular immune system and the innate immune response prove their roles in diagnosing CMV reinfection and monitoring the therapeutic regime to control CMV. Interactions among the components of cellular immunity encounter CMV reactivation provide a strong treatment management plan for clinical decisions about antiviral therapy against CMV. Natural killer (NK) cells, as essential effector cells, present potentially antiviral activity through distinct subpopulations. CCR7expressing NK cells were identified by high cytotoxicity and functionality among NK cell subsets. Here, we explored the correlation between CCR7+ expressing NK cells with viral load in CMV reactivated-kidney transplant recipients. MATERIALS AND METHODS: A cross-sectional study was conducted among ten CMV reactivated KTRs. The CMV DNA copy number was evaluated utilizing real-time PCR.NK cell phenotypic profiling was done using flow cytometry. RESULTS: Increasing of CMV viral load in CMV reactivated KTRs had a negative correlation with CCR7+CD57+ CD56/CD16+ NK cell (P < .05 r = -0.7) after CMV reactivation. Significantly increased level of CCR7-CD57- CD56/CD16+ NK cell was associated with CMV viral load within CMV reactivated KTRs (P < .05, r = 0.68). CONCLUSION: CCR7 expression is associated with CMV reactivation, which offers a new aspect of CMV-associated immunity within the NK cell compartment.  DOI: 10.52547/ijkd.6721.

Oncogenic and tumor suppressor genes expression in myeloproliferative neoplasms: The hidden side of a complex pathology.

BACKGROUND: The present study aimed to explore the changes in the expressions of six tumor-related genes in myeloproliferative neoplasms (MPNs). The study population included 130 patients with MPNs (52 with chronic myeloid leukemia (CML), 49 with essential thrombocythemia (ET), 20 with polycythemia vera (PV), and 9 with primary myelofibrosis (PMF)) and 51 healthy individuals. METHODS: The expression profiling of six genes (ADAMTS18, CMTM5, CDKN2B, DCC, FHIT, and WNT5B) in the peripheral blood granulocyte cells was explored by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: The patients with MPNs showed significant downregulation of CMTM5 (EFC = 0.66) and DCC (EFC = 0.65) genes in contrast to a non-significant upregulation of ADAMTS18, CDKN2B, FHIT, and WNT5B genes. Downregulation of DCC was consistent in all subtypes of MPN (EFC range: 0.591-0.860). However, CMTM5 had a 1.22-fold upregulation in PMF in contrast to downregulation in other MPN subtypes (EFC range: 0.599-0.775). The results revealed a significant downregulation in CMTM5 and DCC at below 60-years of age. Furthermore, female patients showed a clear-cut downregulation in both CMTM5 and DCC (EFC DCC: 0.436 and CMTM5: 0.570), while male patients presented a less prominent downregulation with a borderline p-value only in DCC (EFC: 0.69; p = 0.05). CONCLUSIONS: Chronic myeloid leukemia cases showed a significant upregulation of WNT5B, as a known oncogenesis gene. Two tumor suppressor genes, namely DCC and CMTM5, were downregulated in the patients with MPNs, especially in females and patients below 60 years of age.