Assessment of interleukin-17A, C5a and RANTES for early diagnosis of neonatal sepsis - a preliminary study.

The aim of the present study was to investigate serum levels of novel markers: interleukin 17A (IL-17A), anaphylatoxin C5a and chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in neonates with clinically suspected early-onset neonatal sepsis (EONS), and to compare their values with those of non-infected neonates. Eighteen neonates with clinical signs and symptoms of EONS were enrolled in this study. Fifty healthy, non-infected neonates served as the control group. In all neonates serum levels of IL-17A, C5a and RANTES were measured by solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). At the time of investigation serum levels of anaphylatoxin C5a were significantly higher in neonates with clinical symptoms of EONS than in non-infected neonates (median 65.35 vs. 50.4 ng/ml, p = 0.034), whereas levels of RANTES were similar and levels of IL-17A were under detection limit of the method. Based on these preliminary results, serum levels of C5a may be a useful marker of inflammation in early onset neonatal sepsis. Because traditional methods of microbiological diagnostics in EONS are frequently unsuccessful, the search for an alternative laboratory biomarkers is of great clinical importance. Thus, there is a strong need for further studies evaluating usefulness of this anaphylatoxin in EONS diagnosis on a larger group of patients.

Human cytomegalovirus UL55, UL144, and US28 genotype distribution in infants infected congenitally or postnatally.

Cytomegalovirus (CMV) is the most common cause of congenital infection. This pathogen exhibits extensive genetic variability in the genes that encode structural envelope glycoproteins, regulatory proteins, and proteins that contribute to immune evasion. However, the role of specific viral strains in the outcome of congenital CMV infection is unclear. Variation in the UL55 gene encoding glycoprotein B (gB), the UL144 gene encoding TNF α-like receptor, and the US28 gene encoding ß-chemokine receptor was determined in 60 newborn infants with congenital CMV infection and 90 infants with postnatal or undefined CMV infection. CMV polymorphisms were studied in relation to disease outcome and viral load. Genotyping was performed by a sequencing analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. The results demonstrated that (1) the UL55 and US28 genotype distributions were similar among the group of congenital and postnatal CMV infection; (2) the UL144 B1 genotype was more prevalent in congenital than in postnatal infection and was detected in 70% of newborns with asymptomatic congenital infection; and (3) none of the examined genotype was significantly linked with symptomatic CMV infection. No relationship was observed between genotype and viral load. The results revealed that UL55, UL144, and US28 polymorphisms are not associated with the outcome of CMV infection in infants, but the presence of UL144 B1 genotype might be virological marker of asymptomatic infection at birth.

Cytomegalovirus glycoprotein H genotype distribution and the relationship with hearing loss in children.

Cytomegalovirus (CMV) is a leading cause of congenital infection and a leading infectious cause of hearing loss in children. The ORF UL75 gene encodes envelope glycoprotein H (gH), which is essential for CMV entry into host cells and the target of the immune response in humans. However, the distribution of gH variants and the relationship between the viral genotype, viral load, and sequelae in children infected with CMV is debated. The UL75 genetic variation of CMV isolates from 42 newborns infected congenitally with CMV and 93 infants with postnatal or unproven congenital CMV infection was analyzed. Genotyping was performed by analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. There were no differences in the distribution of gH genotypes in the children infected congenitally and postnatally. Mixed-genotype infections with both gH1 and gH2 variants were detected in approximately 25% of the examined patients. No relationship between UL75 gene polymorphisms and the symptoms at birth was observed. The results suggest that the infection with gH2 genotype diminishes the risk of hearing loss in children (P = 0.010). In addition, sensorineural hearing loss was associated with CMV gH1 genotype infection in infants (P = 0.032) and a high viral load in urine (P = 0.005). In conclusion, it was found that the gH genotype does not predict clinical sequelae in newborn infants following congenital CMV infection. However, these results suggest that the gH genotype might be associated with hearing loss in children.

Incidence of SARS-CoV-2 infection among healthcare workers before and after COVID-19 vaccination in a tertiary paediatric hospital in Warsaw: A retrospective cohort study.

A retrospective observational study was conducted among healthcare workers (HCWs) in a tertiary paediatric hospital. The study covered the period before and after implementation of the vaccination programme and evaluated the incidence of new SARS-CoV-2 infections in both periods. Risk factors of the new SARS-CoV-2 infection and COVID-19 vaccine effectiveness was also assessed in a real-world setting. The overall incidence of SARS-CoV-2 infections among HCWs in the study period was 19.4% with a high proportion of asymptomatic individuals (45.1%). The incidence before vaccination was 16.6% and nurses had a higher risk of infection, while physicians had a reduced risk (OR 1.80, 95% CI 1.29-2.52; and OR 0.45, 95% CI 0.30-0.68). Within two months of implementation, the programme achieved a high (88.9%) vaccination coverage in our cohort, although some disparities in vaccination rates were observed. In particular, older individuals, physicians, those working in clinical settings, and those previously uninfected were more likely to be vaccinated. The overall incidence of SARS-CoV-2 infection after vaccination deployment was 6.4% (40.0% in unvaccinated individuals and 3.2% in individuals vaccinated with at least one dose). The estimated vaccine efficacy was high (95.0%) in fully vaccinated HCWs and similar to those observed previously in clinical trials and real-world settings.

Epstein-Barr virus gene expression and latent membrane protein 1 gene polymorphism in pediatric liver transplant recipients.

Immunosuppressed pediatric transplant recipients are at risk of developing Epstein-Barr virus (EBV)-associated complications (such as post-transplant lymphoproliferative disorders). Monitoring of the EBV DNA level in blood alone has a low predictive value for the post-transplant course of EBV infection and its complications. Therefore, additional prognostic markers are widely sought. The study aim was to analyze EBV gene expression patterns and LMP1 polymorphism in relation to EBV DNA levels in pediatric liver transplant recipients. EBV load measurement, LMP1 variant, and gene expression analysis were performed in collected prospectively multiple blood samples from 30 patients. Several distinct patterns of EBV gene expression were identified: latency 2 (71%), latency 3 (13%), latency 0 (11%), and lytic infection (5%). In most children's multiple blood samples, both EBV gene expression patterns and expression levels of individual EBV genes varied significantly over time. EBV gene expression patterns were not associated with the EBV load. However, the viral load correlated with the LMP1 and LMP2 expression (r = 0.34; P = 0.006, and r = 0.45; P = 0.001, respectively). Two variants of the LMP1 gene were detected, and they were consistent over time in individual patients. A wild type of LMP1 was associated with higher EBV-DNA loads (P = 0.03). This indicates that EBV infection in immunosuppressed patients is a very dynamic process, but changes in the state of EBV infection do not influence significantly the viral load. The latter, however, can be associated with the activity of LMP1 and LMP2 genes, as well as polymorphism of LMP1.

Prevalence of IgG antibodies against SARS-CoV-2 among healthcare workers in a tertiary pediatric hospital in Poland.

Data on the prevalence of the SARS-CoV-2 antibody in healthcare workers (HCWs) is scarce, especially in pediatric settings. The purpose of this study was to evaluate SARS-CoV-2 IgG-positivity among HCWs of a tertiary pediatric hospital. In addition, follow-up of the serological response in the subgroup of seropositive HCWs was analysed, to gain some insight on the persistence of IgG antibodies to SARS-CoV-2. We performed a retrospective analysis of voluntary SARS-CoV-2 IgG testing, which was made available free of charge to HCWs of the Children's Memorial Health Institute in Warsaw (Poland). Plasma samples were collected between July 1 and August 9, 2020, and tested using the Abbott SARS-CoV-2 IgG assay. Of 2,282 eligible participants, 1,879 (82.3%) HCWs volunteered to undergo testing. Sixteen HCWs tested positive for SARS-CoV-2 IgG, corresponding to a seroprevalence of 0.85%. Among seropositive HCWs, three HCWs had confirmed COVID-19. Nine (56.3%) of the seropositive HCWs reported neither symptoms nor unprotected contact with confirmed SARS-CoV-2 cases in the previous months. A decline in the IgG index was observed at a median time of 86.5 days (range:84‒128 days) after symptom onset or RT-PCR testing. Further studies are necessary to elucidate the duration of persistence of anti-SARS-CoV-2 antibodies, as well as the correlation between seropositivity and protective immunity against reinfection. Regardless of the persistence of antibodies and their protective properties, such low prevalence indicates that this population is vulnerable to a second wave of the COVID-19 pandemic.

Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection.

BACKGROUND: There are limited data on factors that determine viral load (VL) in congenital cytomegalovirus (cCMV) infection. Single nucleotide polymorphisms (SNPs) might influence individual host response to infection. This study aimed to investigate the association between SNPs in genes encoding cytokines or cytokine receptors and VL in newborns with cCMV. MATERIAL AND METHODS: Eight polymorphisms (IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791 and TLR9 rs352140) were analyzed in study population of 233 newborns, including 92 cCMV-infected newborns (73 symptomatic and 19 asymptomatic) by TaqMan SNP Predesigned Genotyping Assays. The association analysis was performed using SNPStats software and STATISTICA10. RESULTS: The association between IL12B polymorphism and viruria was observed (p = 0.029). In multiple comparison tests, heterozygous T/G genotype of IL12B was associated with higher viruria than T/T genotype (p = 0.041) in cCMV-infected newborns. In allele analysis, T allele of IL12B was associated with higher viremia (p = 0.037) in symptomatic newborns. We observed higher VL in symptomatic newborns in comparison to asymptomatic (median viremia: 1.7 × 104 copies/mL vs. 2.0 × 103 copies/mL (p = 0.002), median viruria: 1.0 × 107 copies/mL versus 6.9 × 105 copies/mL (p = 0.001), respectively). CONCLUSIONS: IL12B rs3212227 was associated with VL in cCMV. Symptomatic newborns had significantly higher viremia and viruria. The role of SNPs in pathogenesis of cCMV warrants further investigations.

Single Nucleotide Polymorphisms of Interleukins and Toll-like Receptors and Neuroimaging Results in Newborns with Congenital HCMV Infection.

Congenital cytomegalovirus infection (cCMV) is the most common intrauterine infection with central nervous system (CNS) involvement. There is limited data on the associations between Single Nucleotide Polymorphisms (SNPs) in genes involving the first-line defense mechanism and the risk of CNS damage during cCMV. We investigated the associations between neuroimaging findings and SNPs in genes encoding the following cytokines and cytokine receptors in 92 infants with cCMV: interleukins (IL1B rs16944, IL12B rs3212227, IL28B rs12979860), C-C motif chemokine ligand 2 (CCL2 rs1024611), dendritic cell-specific intercellular adhesion grabbing non-integrin (DC-SIGN rs735240), Toll-like receptors (TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140). The SNP of IL1B rs16944 (G/A) was associated with a reduced risk of ventriculomegaly on MRI (OR = 0.46, 95% CI, 0.22-0.95; p = 0.03) and cUS (OR = 0.38, 95% CI, 0.0-0.93; p = 0.034). Infants carrying heterozygous (T/C) genotype at IL28B rs12979860 had an increased risk of cystic lesions on cUS (OR = 3.31, 95% CI, 1.37-8.01; p = 0.0064) and MRI (OR = 4.97, 95% CI, 1.84-13.43; p = 0.001), and an increased risk of ventriculomegaly on MRI (OR = 2.46, 95% CI, 1.03-5.90; p = 0.04). No other associations between genotyped SNPs and neuroimaging results were found. This is the first study demonstrating new associations between SNPs of IL1B and IL28B and abnormal neuroimaging in infants with cCMV.

The Limitations of Cytomegalovirus DNA Detection in Cerebrospinal Fluid of Newborn Infants With Congenital CMV Infection: A Tertiary Care Neonatal Center Experience.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection of the central nervous system (CNS) can cause ventriculomegaly, gliosis, calcifications and cortical defects. Detection of CMV DNA in cerebrospinal fluid by PCR (CSF-CMV-PCR) is a marker of CNS involvement. OBJECTIVE: To evaluate a diagnostic value of the positive CSF-CMV-PCR in cCMV. METHODS: Analysis of clinical, laboratory, neuroimaging and single-nucleotide polymorphisms (SNPs) data according to the results of CSF-CMV-PCR were performed in infants with cCMV. RESULTS: A total of 168 infants were included; 145 (86.3%) had negative and 23 (13.7%) had positive CSF-CMV-PCR results. Associations between the positive CSF-CMV-PCR results and prematurity (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 1.30-8.07), microcephaly (OR = 5.67; 95% CI: 2.08-15.41), seizures (OR = 4.15; 95% CI: 1.10-15.67), sensorineural hearing loss (OR = 6.6; 95% CI: 2.49-17.46), splenomegaly (OR = 8.13; 95% CI: 3.12-21.16), hepatitis (OR = 10.51; 95% CI: 3.31-33.35), petechiae (OR = 10.21; 95% CI: 3.78-27.57) and heterozygous T/C genotype at TLR4rs4986791 (OR = 7.88; 95% CI: 1.55-40.12) were observed. When using a multivariate logistic regression analysis, only the presence of severe sensorineural hearing loss (OR = 7.18; 95% CI: 1.75-29.34, P = 0.006), cystic lesions on MRI (OR 5.29; 95% CI: 1.31-21.36, P = 0.02), and calcifications on MRI (OR = 7.19; 95% CI: 1.67-30.97, P = 0.008) remained as the significant independent predictors of the positive CSF-CMV-PCR results. CONCLUSIONS: The detection of CMV DNA in CSF is associated with a higher rate of CNS damage including abnormal MRI neuroimaging and severe hearing loss. Therefore, detection of CMV DNA in CSF may be considered as a marker of severe CNS injury in cCMV infection. However, the very low prevalence of the positive CSF-CMV-PCR results, even in infants with proven CNS involvement, may imply its limited role in clinical practice.

Nijmegen breakage syndrome: Long-term monitoring of viral and immunological biomarkers in peripheral blood before development of malignancy.

Selected viruses and immune parameters were monitored in 57 patients with Nijmegen breakage syndrome as a proposed tool for early detection of changes preceding development of malignancy. The following parameters were analysed: (1) viral infections; (2) monoclonal proteins; and (3) B-cell and T-cell receptor gene rearrangements in peripheral blood lymphocytes. Viral infections were detected in 68.4% of patients with a predominance of EBV (63.2%), followed by HBV (19.2%) and HCV (8.8%). Monoclonal gammopathy detected in 38.6% of cases correlated with the presence of EBV DNA (p=0.002) and HCV RNA (p=0.04). Clonal Ig and/or TCR gene rearrangements occurred in 73.9% of patients. The presence of at least one of the studied parameters preceded the development of malignancy in 22 patients. Systematic PCR analysis for viral infections and Ig/TCR gene rearrangements, supplemented by detection of monoclonal proteins, is advantageous in monitoring NBS patients before severe complications of the disease, including cancer, appear.

Long-term monitoring of Epstein-Barr virus DNA load and humoral parameter abnormalities in pediatric liver transplant recipients before development of malignancy.

EBV loads and abnormalities of humoral responses were monitored in 51 pediatric liver transplant recipients as a proposed non-invasive laboratory tool for early detection of changes preceding severe clinical complications. EBV DNA load, concentrations of IgM, IgG, IgA, and monoclonal proteins were determined in each blood sample. EBV DNA was detected in 70.6% of the children, dysgammaglobulinemia of one or more Ig isotype was present in 41.2% of them. MG detected in 43.1% of patients correlated with the presence of EBV DNA (p = 0.003) and was usually preceded by hypergammaglobulinemia. The median maximum EBV load was significantly higher in EBV DNA+/MG+ patients than in EBV DNA+/MG- patients (p = 0.04), although there was no correlation between current viral load and appearance of MG. Four of 15 EBV DNA-negative patients developed MG, preceded by hypergammaglobulinemia in two. Minimization or cessation of immunosuppression in 42 patients, in whom abnormal biomarkers and/or clinical symptoms raised suspicion of disease progression, permitted complete resolution of abnormalities in all but one patient who developed B-NHL and died. Simultaneous monitoring of protein profiles and EBV DNA load together with thorough physical evaluation of children after LTx is important for early implementation of suitable preemptive therapy.

Antiviral treatment in congenital HCMV infection: The six-year experience of a single neonatal center in Poland.

BACKGROUND: Antiviral treatment is recommended for symptomatic newborns with congenital cytomegalovirus infection (cCMV). OBJECTIVES: To compare 2 treatment methods in neonates with cCMV - ganciclovir-based therapy (intravenous ganciclovir (GCV) or sequential GCV + valganciclovir (VGCV) therapy) with oral VGCV-based therapy - in Polish neonates. MATERIAL AND METHODS: A total of 98 symptomatic infants with cCMV (positive HCMV DNA in urine ≤21st day of life) hospitalized in the neonatal intensive care unit (NICU) between 2012 and 2017 were enrolled. Clinical characteristics, the viral load in blood and urine, hematological and biochemical tests, neuroimaging results, and the length of hospitalization were compared between the study groups at baseline and at the 2nd hospitalization. RESULTS: In 2012, GCV was used in 57% of the cases, sequential therapy in 33% and VGCV in 10%. In 2017, VGCV monotherapy was used in 83% of the infants treated. Valganciclovir treatment allowed the length of hospitalization to be shortened over 2.5 times during the six-year observation period. Infants treated intravenously had lower birth weights and head circumferences, and more frequently presented splenomegaly, petechiae, thrombocytopenia, and hepatitis. The baseline viral load in the blood and urine were similar in both groups, but at follow-up visits 4-6 weeks later, a viral load about 70 times lower was observed in the blood of the VGCV-based group (1029 viral copies/mL compared to 72,188 viral copies/mL in the GCV-based group; p = 0.04). The prevalence of neutropenia was similar in both groups at the follow-up visits. CONCLUSIONS: Valganciclovir became the first line of antiviral therapy in cCMV in the study population. Compared to GCV-based therapy, VGCV monotherapy allowed shorter hospital stays and reduced the viral load in blood due to continuing treatment at home. Valganciclovir monotherapy did not provoke more side effects such as neutropenia. Intravenous GCV is still suitable for patients with severe disseminated disease, born prematurely, with low birth weights, or not tolerating enteral feeding. In those infants, the sequential therapy seems to be optimal.

Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection.

Congenital cytomegalovirus (cCMV) infection is the most common intrauterine infection. A non-specific immune response is the first line of host defense mechanism against human cytomegalovirus (HCMV). There is limited data on associations between Single Nucleotide Polymorphisms (SNPs) in genes involving innate immunity and the risk and clinical manifestation of cCMV infection. The aim of the study was to investigate association between selected SNPs in genes encoding cytokines and cytokine receptors, and predisposition to cCMV infection including symptomatic course of disease and symptoms. A panel of eight SNPs: IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140 was analyzed in 233 infants (92 cCMV-infected and 141 healthy controls). Associations between genotyped SNPs and predisposition to cCMV infection and symptoms were analyzed. The association analysis was performed using SNPStats software. No statistically significant association was found between any genotyped SNPs and predisposition to cCMV infection and symptomatic course of disease. In relation to particular symptoms, polymorphism of IL12B rs3212227 was linked to decreased risk of prematurity (OR = 0.37;95%CI,0.14-0.98;p = 0.025), while polymorphism of IL1B rs16944 was linked to reduced risk of splenomegaly (OR = 0.36;95%CI,0.14-0.98; p = 0.034) in infants with cCMV infection. An increased risk of thrombocytopenia was associated with IL28B rs12979860 polymorphism (OR = 2.55;95%CI,1.03-6.32;p = 0.042), while hepatitis was associated with SNP of TLR4rs4986791 (OR = 7.80;95%CI,1.49-40,81; p = 0.024). This is the first study to demonstrate four new associations between SNPs in selected genes (IL1B, IL12B, IL28B, TLR4) and particular symptoms in cCMV disease. Further studies on the role of SNPs in the pathogenesis of cCMV infection and incorporation of selected SNPs in the clinical practice might be considered in the future.

Distribution of the CMV glycoprotein gH/gL/gO and gH/gL/pUL128/pUL130/pUL131A complex variants and associated clinical manifestations in infants infected congenitally or postnatally.

Human cytomegalovirus (CMV) is a major cause of morbidity in fetuses following intrauterine infection. The glycoprotein (g) envelope trimeric gH/gL/gO and pentameric gH/gL/pUL128/pUL130/pUL131A complexes are required for CMV entry into fibroblasts and endothelial/epithelial cells, respectively, and both are targets for neutralizing antibodies. The role of sequence variability among viral strains in the outcome of congenital CMV infection is controversial. Variation in the CMV UL75 gene encoding glycoprotein H (gH), the UL115 (gL), the UL74 (gO), and the UL128 locus (UL128L) encoding three structural proteins (pUL128, pUL130, and pUL131A) was determined in 82 newborns with congenital CMV infection and 113 infants with postnatal or unproven congenital CMV infection. Genotyping was performed by sequencing analysis of PCR-amplified fragments and the PCR-restriction fragment length polymorphism (RFLP) method, and the viral load was measured by quantitative real-time PCR. The obtained results demonstrated that (1) different CMV variants and mixed CMV infections can be detected in newborns infected congenitally; (2) the gH1 genotype, UL130 variant 6, and UL131A variant 1 were associated with some signs/symptoms within cohort of pediatric patients, mainly consisting of infants with symptomatic CMV infection. The results revealed that pUL130, pUL131A, and gH polymorphisms seemed to be associated with the outcome of CMV infection in infants.

Cytomegalovirus alpha-chemokine genotypes are associated with clinical manifestations in children with congenital or postnatal infections.

Human cytomegalovirus (HCMV) is the leading cause of congenital infections. The aim of our study was to determine the prevalence of genotypes based on the highly polymorphic UL146 and UL147 HCMV genes and the relationship between the genotype and symptoms or viral load. We analyzed samples from 121 infants with symptomatic HCMV infection, including 32 congenitally infected newborns. The G7 and G5 genotypes were predominant in postnatal infection, whereas the G1 genotype was prevalent in congenital infection. Central nervous system (CNS) damage and hepatomegaly were detected more frequently among children infected with the G1 genotype than in those infected by other genotypes. An association between the viral genotype and viruria level was found. There was a strong correlation between HCMV genotypes determined through the UL146 and UL147 sequences (ĸ=0.794). In conclusion, we found that certain vCXCL genotypes are associated with clinical sequelae following HCMV infection.

Distribution of cytomegalovirus gN variants and associated clinical sequelae in infants.

BACKGROUND: Human cytomegalovirus (HCMV) is the most widespread cause of congenital infection. The effects of various viral strains and viral loads on the infection outcome have been under debate. OBJECTIVES: To determine the distribution of gN variants in HCMV strains isolated from children with congenital or postnatal infection and to establish the relationship between the viral genotype, the viral load, and the sequelae. STUDY DESIGN: The study population included congenitally HCMV-infected newborns and children with postnatal or unproven congenital HCMV infection. The genotyping was performed by RFLP analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. RESULTS: Our results demonstrated that the HCMV genotypes gN3b, gN4b, and gN4c were prevalent in the patients examined. There were no differences in the distributions of gN genotypes in the congenitally and postnatally infected children. Multiple HCMV strains were detected in both groups of children. A significant association between the HCMV gN4 genotype and the incidence of neurological disorders was observed (p=0.045). Our results suggest that the detection of the gN2 or the gN4 genotype may be indicative of serious manifestations in children. In contrast, the gN3b and the gN1 genotypes represent less pathogenic HCMV strains. The HCMV load in urine was significantly higher in children with congenital infection compared with children with postnatal infection. No correlation was found between the viral load and the genotype. CONCLUSION: Our results suggest that the gN genotype may be a virological marker of symptomatic HCMV infection in newborns.

The impact of cytokine gene polymorphisms on Epstein-Barr virus infection outcome in pediatric liver transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV) is associated with most cases of the post-transplant lymphoproliferative disorders developed during the first year after transplantation. The high EBV DNA load constitutes a major risk for the development of EBV-related lymphoproliferations. However, among transplant recipients there are patients with a chronically high viral load (CHVL) who do not develop lymphoproliferations. The polymorphism within cytokine genes might influence the susceptibility to, and contribute to the pathogenesis of the disease. OBJECTIVES: The aim of this study was to analyze the genetic polymorphism in the selected cytokines with regard to EBV infection outcome in children after liver transplantation (LTx). STUDY DESIGN: Thirteen cytokine/cytokine receptor polymorphisms were genotyped in 170 children after LTx, and related to: EBV DNAemia, CHVL onset and the length of CHVL carriage. RESULTS: The study revealed: the protective effect of rare homozygous and heterozygous IL-1ß-511 and IL-1 receptor antagonist (IL-1RN VNTR) genotypes against viremia within the first year after LTx (OR=0.28, p=0.0007 and OR=0.35, p=0.009, respectively); the protective effect of CC chemokine ligand 2 (CCL2)+1543CT and TT genotypes against CHVL onset (OR=0.38, p=0.042); and the prolonged CHVL-resolution in IL12B 3'untranslated region (3'UTR) AC individuals (p=0.034). CONCLUSIONS: This data suggests that carriage of IL-1ß-511CT/TT and/or IL-1RN VNTR 1.2/2.2 genotype may be beneficial for combating EBV infection. This is the first study reporting the association of CCL2 and IL12B gene polymorphisms with the CHVL carriage in pediatric LTx recipients.

Mannan-binding lectin-2 (MBL2) gene polymorphisms in prenatal and perinatal cytomegalovirus infections.

Cytomegalovirus (CMV) is the leading cause of congenital infections among neonates. About 10% of newborns with such an infection have clinical symptoms at birth and about 1% of infected fetuses die due to developmental malformations. Mannan-binding lectin (MBL) is considered to be an important factor in innate immunity. Its deficiency is believed to predispose to various (including viral) infections. The aim of this study was to investigate the possible role of MBL2 gene polymorphisms in prenatal and perinatal CMV infections. The frequencies of MBL2 gene exon 1 mutations as well as MBL deficiency-associated variants (LXPA/O+O/O) among newborns with confirmed cytomegalovirus infection were not significantly lower than among non-infected individuals. The distribution of MBL2 haplotypes was similar between the groups studied. These data suggest MBL does not have a major influence on susceptibility to prenatal or perinatal CMV infections.