Cytomegalovirus Immunoglobulin G Research Articles

Cytomegalovirus Immunoglobulin G Levels and Subclinical Arterial Disease among People Living with HIV in Botswana: A Cross-Sectional Study.

Cytomegalovirus (CMV) has been linked with increased cardiovascular risk and monocyte activation in people living with HIV (PLWH). This cross-sectional study aimed to compare CMV immunoglobulin G (IgG) levels between combined antiretroviral therapy (cART)-treated PLWH versus ART-naïve PLWH and those without HIV, and to investigate their associations with biomarkers of endothelial injury and carotid atherosclerosis, in Gaborone, Botswana. All participants were between 30 and 50 years old. Carotid intimal media thickness (cIMT) and biomarkers of endothelial injury and monocyte activation were also assessed. The association between quantitative CMV IgG and cardiovascular disease risk was assessed in multivariate logistic regression analysis. The results showed that the mean CMV IgG level among ART-naïve participants was significantly higher than both the cART group and controls. However, CMV IgG levels did not differ significantly between the controls and cART groups. Among PLWH, CMV IgG levels were associated with ICAM-1 levels and cIMT. Increases in CMV IgG among ART-naïve participants were significantly associated with increases in log VCAM-1. In conclusion, CMV IgG levels are elevated among PLWH in sub-Saharan Africa, and higher levels are associated with biomarkers of endothelial injury and cIMT. Future research should investigate the long-term impact of elevated CMV IgG among PLWH.

Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV.

Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010-2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6-53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P = .002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P = .002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11-4.27) and death (aHR, 1.99; 95% CI, 1.14-3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P = .75). CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted.

Biological expressions of early life trauma in the immune system of older adults.

Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

Cytomegalovirus infection associated with smaller cerebellum in severe mental illness

IntroductionPostnatal cytomegalovirus (CMV) infection of immunocompetent hosts is usually inapparent but typically results in lifelong latency. Congenital CMV infections as well as CMV infections in patients with immunodeficiencies have been linked to major cerebellar pathology. Patients with severe mental illness have been repeatedly found to have smaller cerebellum, and they may be particularly susceptible to CMV infections. Finally, both animal and human studies have shown a differential male and female immune response to CMV.ObjectivesWe evaluated whole cerebellar grey matter volumes (CGMV) in CMV immunoglobulin G (IgG) seropositive (CMV+) and seronegative (CMV-) patients with severe mental illness and healthy controls (HC). We hypothesized that CMV seropositivity, reflecting previous infection and current latency, is associated with smaller CGMV in patients but not in HC, and that such a putative association may be sex-dependent.MethodsWe included 529 adult patients with severe mental illness (CMV+ 57%, women 48%), i.e., 324 patients with schizophrenia spectrum disorders and 205 patients with bipolar spectrum disorders, and 494 HC (CMV+ 56%, women 45%). MRI scans were obtained with a 1.5T Siemens scanner (n=596) and two 3.0T General Electric scanners (n=427), and processed with FreeSurfer v6.0. Circulating CMV IgG concentrations were measured with immunoassays. In age-, scanner- and estimated total intracranial volume-adjusted analyses of covariance (ANCOVAs), we investigated main and interaction effects of CMV status and sex on CGMV in patients and HC.ResultsCMV+ patients had smaller CGMV than CMV- patients (p=0.042). There was no CGMV difference between CMV+ and CMV- HC (p=0.858). The adjusted CGMV means in CMV+ patients and CMV- patients were 115078 mm3 and 116725 mm3, respectively (p=0.042); the adjusted CGMV means in CMV+ and CMV- HC were 117980 mm3 and 117840 mm3, respectively (p=0.858) (Image). Among patients, a trend towards CMV-by-sex interaction (p=0.073) was found. Post-hoc analyses showed a significant CMV-CGMV association in the female patient group (p=0.005), with no association among male patients (p=0.840).Image:ConclusionsCMV IgG seropositivity is associated with smaller cerebellum in severe mental illness, an effect driven by the female patients, but not among HC. This may indicate a CMV-related deleterious impact on cerebellum restricted to patients.Disclosure of InterestNone Declared

Breast Milk and Saliva for Postnatal Cyto†megalovirus Screening among Very Low Birth Weight Infants.

The optimal approach to managing postnatal cytomegalovirus disease (pCMV) among very low birth weight (VLBW) infants remains unknown. Methods to facilitate screening are needed. Determine whether mother's milk and infant saliva can be used to reliably identify maternal cytomegalovirus (CMV) serostatus and detect infant pCMV acquisition. This was a single-center, prospective cohort study of VLBW infants, and their mothers, born between 2017 and 2020. Maternal milk samples were tested for CMV immunoglobulin G (IgG) using a CMV glycoprotein B binding enzyme-linked immunosorbent assay and the results were compared with maternal serum CMV IgG results. Biweekly paired saliva and urine samples were collected from infants born to mothers with positive or unknown CMV serostatus. Saliva samples were tested for CMV DNA by quantitative real-time polymerase chain reaction (PCR) and compared with urine CMV qualitative PCR results obtained from a clinical laboratory. Among 108 infants without congenital CMV included in the study, 10 (9%) acquired pCMV. Both milk and blood CMV serology results were available for 70 mothers. Maternal milk antibody testing had a sensitivity of 97.2% (95% CI: 85.5-99.9%) and specificity of 91.2% (95% CI: 76.3-98.1%) in establishing CMV serostatus. Paired serially collected saliva and urine samples (n = 203) were available for 66 infants. Saliva PCR had a sensitivity of 30.0% (95% CI: 6.7-65.2%) and specificity of 92.7% (95% CI: 88.1-96.0%) in detecting pCMV acquisition. Maternal breast milk is a reliable alternative sample to determine CMV serostatus. Serial testing of infant saliva was not adequately sensitive for identifying pCMV acquisition in preterm infants.

Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV).

Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque. The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry. Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5. No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events. NCT02344290.

Cytomegalovirus Infection in Ulcerative Colitis: An Ambispective Study from a Single Center

Abstract Background and Objectives Cytomegalovirus (CMV) is often detected in colonic tissue of patients with inflammatory bowel disease. Its role as a “bystander” or “culprit” in ulcerative colitis (UC) flares is unclear. The aim of the study is to detect the prevalence and outcomes of CMV infection in UC Materials and Methods All adult patients (both retrospective and prospective), diagnosed with UC in a tertiary care center, were included. Patients underwent colonic biopsies for histopathological examination for CMV. CMV immunoglobulin G (IgG) was also tested to ascertain seroprevalence in this population. CMV infection was defined as presence of CMV inclusions in histopathology. Treatment outcomes were defined as remission, clinical improvement, and partial response. The number of flares and outcomes of disease activity in terms of flare of disease, hospitalization, need of colectomy, and mortality was noted at follow-up. Results A total of 58 patients of UC were included (mean age was 37.3 years, males—66%). Serum CMV IgG was positive in all patients. Twelve patients (20.6%, 9 males) with active UC were found to have CMV infection in histopathology specimens with hematoxylin and eosin staining. Two-third of patients (8/12) had severe disease, while the remaining (4/12) had moderate disease activity. Nine patients (9/12) with CMV colitis achieved complete remission with standard treatment without antiviral therapy. Of the three patients who needed antiviral therapy, two underwent colectomy in follow-up. CMV-positive patients to be predominantly male (p = 0.58) had more frequent relapses (p = 0.08) and were hospitalized for their flares (p = 0.06) when compared with CMV-negative patients. None of these factors were found to be statistically significant. Conclusion CMV infection was found in one-fifth of patients of UC with flare. All patients with CMV infection had moderate-to-severe disease. Majority achieved remission without the need of antiviral therapy.

Cytomegalovirus infection associated with lower IQ in adolescent patients with schizophrenia spectrum disorders: A preliminary report

Cytomegalovirus (CMV) infection of immunocompetent hosts is usually inapparent, but typically results in a non-silent chronic latency which is considerably more active than previously considered. In adults with schizophrenia spectrum disorders, CMV latent infection has been associated with cognitive disturbance including lower intelligent quotient (IQ). We hypothesized that the same pattern will be present in adolescent patients with schizophrenia spectrum disorders (early-onset non-affective psychosis). We included 17 adolescents with schizophrenia spectrum disorders (10 patients with schizophrenia, one patient with schizoaffective disorder and six patients with psychosis not otherwise specified), mean age 16.7 years, females 71% and CMV seropositivity 35%. Current IQ was estimated with the Wechsler Abbreviated Scale of Intelligence. CMV immunoglobulin G (IgG) concentrations were measured by solid-phase immunoassays and expressed as dichotomous measures (seropositive/CMV + vs. seronegative/CMV-). CMV + patients (mean IQ 91) had significantly lower full-scale IQ than CMV- patients (mean IQ 110) (20 units difference; p < 0.001). Post-hoc analyses showed that CMV + patients had both lower performance and lower verbal IQ relative to CMV- patients (p = 0.001 and 0.049, respectively). In this preliminary report, we found that CMV IgG seropositivity, reflecting previous CMV infection and current latency, was associated with lower IQ. This may be indicative of an unfavorable impact of CMV infection on general intelligence in early-onset non-affective psychosis.

Progressive familial intrahepatic cholestasis-2 and concomitant cytomegalovirus infection in an infant: a case report

Conjugated hyperbilirubinemia (CH) in infancy can have anatomic, infectious, auto-immune and metabolic causes. We reported a case of CH presented at 2 months and 20 days, with clinical jaundice and evidence of acute on chronic liver failure. Significant history of elder sibling death at the age of 5 months due to hepatic failure and intracranial bleed was present. Investigations revealed a normal gamma glutamyl transpeptidase (GGT) levels. Toxoplasmosis, rubella, cytomegalovirus and herpes simplex (TORCH) panel showed cytomegalovirus (CMV) immunoglobulin M (IgM), immunoglobulin G (IgG) and deoxyribonucleic acid polymerase chain reaction (DNA PCR) positive with mother’s serum CMV IgG, so she was started on oral valganciclovir in addition to other treatment for cholestasis. A clinical exome panel was also sent which showed homozygous two base-pair deletion in exon 27 of the ABCB11 gene [c.3659 3660del (p.Ser1220Ter)] suggestive of benign recurrent intrahepatic cholestasis (BRIC)/progressive familial intrahepatic cholestasis-2 (PFIC-2). The child responded initially to treatment showing reduced serum conjugated bilirubin level and near normalization of INR. However, she was re-admitted with deranged coagulation profile and rising conjugated bilirubin levels after 30 days of discharge and expired due to fulminant hepatic failure with encephalopathy at 6 months of age while she was being prepared for live donor (father) liver transplantation. We presented this case because we found evidence of CMV infection in a child with PFIC-2. The relative contribution of either aetiology needs to be ascertained in view of early recurrence of CH despite standard management protocol including oral valgancyclovir for CMV infection.

The Analysis of Dynamic Changes and Prognosis of Posner-Schlossman Syndrome with Cytomegalovirus Infection and Antiviral Therapy.

Purpose To analyze how keratic precipitate (KP) morphology changes during Posner–Schlossman syndrome (PSS) prognosis and raise medication suggestions on 2% ganciclovir eye drops. Materials and Methods Clinical retrospective cohort study in the Eye & ENT Hospital of Fudan University, Shanghai, China. The attacked eyes of 98 eligible subjects diagnosed unilateral PSS were enrolled between 2016 and 2019. All patients were treated with intraocular pressure-lowering drugs and anti-inflammatory steroids. 2% ganciclovir eye drops were given to cytomegalovirus (CMV) immunoglobulin G (IgG) correction ratio positive patients. Frequent follow-ups and examinations were performed. KP morphology was focused and categorized into coin-shaped, mutton-fat, and pigmented. Medical histories were noted. Multidimensional analysis was given. Results Totally 47 patients in 98 achieved all-KP disappearance. Mean treatment time was (5.13 ± 3.66) weeks. Total KP disappearance was negatively correlated with mutton-fat and pigmented KPs at the first visit (P=0.020, P=0.007) and treatment time was also longer (P=0.018, P=0.014). Mean cumulative steroids dosage for 47 subjects was (159.66 ± 161.84) drops. CMV IgG correction ratio positive patients had smaller corneal endothelial cell density (P < 0.005) and larger cup-to-disc ratio (P=0.017) than negative subjects. Cumulative steroid treatment time was longer in the CMV-positive group, and overall dosage was also larger. However, due to 2% ganciclovir eye drops, daily steroid dosage was lower in the CMV-positive group. Conclusions The disappearance of mutton-fat and pigmented KPs needed longer treatment time. Paired aqueous humor and serum CMV IgG tests were recommended in PSS patients with coin-shaped KPs. 2% ganciclovir eye drops improved prognosis; and steroids dosage reduced significantly.

Polymorphisms of the cytomegalovirus glycoprotein B genotype in patients with Posner-Schlossman syndrome

AimsThe aim of this observational study was to report the distribution of glycoprotein B (gB) genotypes in the eyes of cytomegalovirus (CMV) positive patients with Posner-Schlossman syndrome (PSS), and to...

PREVALENCE AND RISK FACTORS OF CYTOMEGALOVIRUS INFECTION AMONG HAEMODIALYSIS PATIENTS IN SOUTHERN GAZA STRIP, PALESTINE

Introduction: End-Stage Renal Disease patients (ESRD) on maintenance Haemodialysis (HD) are at high risk of acquiring Cytomegalovirus (CMV). The aim of the study was to determine the prevalence and risk factors of CMV infection among HD patients from Nasser's medical complex and Abu Yousef Al Najjar Hospital Southern Gaza strip. Methods: This study was an analytical cross-sectional from March to September 2019. Serum samples were taken from 96 patients (51.1% of them from Nasser medical complex and 48.9% of them from Abu Yousef Al Najjar Hospital), analyzed for CMV-specific immunoglobulin G (IgG) by using the Chemiluminescence immunoassay (CLIA) techniques, questionnaire, and Virological identification. Results: CMV-IgG was detected in 80 patients (83.3%), were 16 patients (16.7%) were CMV IgG Negative. The prominent risk factors were HD duration time, Receiving Injection, and previous blood transfusion. Conclusion: The prevalence of CMV infection among HD patients in the Southern Gaza strip was very high. We recommend that HD patients should be vaccinated against CMV.

Is routine TORCH screening necessary for pregnancy follow-up?

Aim: This study aimed to determine the seroprevalence rates of Toxoplasma gondii, Rubella and Cytomegalovirus (CMV) among the pregnant women who presented to the Ümraniye Training and Research Hospital and to compare the seroprevalence rates with the other studies fromTurkey. Material and method: The antibody levels of all pregnant women presented to the prenatal outpatient clinic between January 1, 2017 and October 30, 2019, for Toxoplasma gondii, Rubella, CMV were obtained retrospectively. Only pregnant women with immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody results of the three viruses were included in the study. If IgM and IgG were both found to be positive, the IgG avidity results were obtained using the Abbott Architect i2000 SR device with enzyme-linked immunosorbent assay (ELISA), following the manufacturer's recommendations. Results: Serological results of pregnant women for Toxoplasma gondii (n = 7535), Rubella (n = 9093), and CMV (n = 2652) were obtained from the hospital records. IgM positivity was found to be 0.6% for Toxoplasma gondii, 0.3% for Rubella, and 2.3% for CMV. IgG positivity was found to be 24% for Toxoplasma gondii, 86.4% for Rubella, and 99% for CMV. IgG avidity test results for Toxoplasma gondii were 5.3% low, 10.5% borderline, and 84.2% high. Rubella IgG and CMV IgG avidity results were all determined following high avidity. Conclusion: Because Toxoplasma IgG seroprevalence is not high, and the treatment of acute toxoplasmosis infection during pregnancy is possible, Toxoplasma screening should be recommended to all pregnant women. Because the immunity to the Rubella virus is still not at the desired level in our country, we believe screening against Rubella is vital during pregnancy. We also believe that routine CMV screening is unnecessary in pregnant women owing to the high seroprevalence of CMV IgG in our country.

Cytomegalovirus-Associated Venous and Arterial Thrombotic Disease.

Background: Cytomegalovirus (CMV) infection has been associated with venous thromboembolism (VTE) and acute coronary syndromes (ACS).Methods: A retrospective study was conducted within the OSF HealthCare System in Peoria, IL. The objectives were to determine the incidence of acute VTE and ACS within one year of CMV testing. The “study group” included patients with positive CMV immunoglobulin M (IgM) or positive CMV polymerase chain reaction (PCR). The “seropositive control” group included patients with positive CMV immunoglobulin G (IgG) and negative IgM. The “seronegative control” group included patients with negative CMV IgG and IgM, or negative PCR.Results: Within one year of CMV infection, 38 of 379 patients (10.0%) developed VTE in the study group compared to 41 of 1334 patients (3.1%) in the seropositive control and 37 of 1249 (3.0%) in the seronegative control. Adjusting for age and gender, both control groups were less likely to have VTE than the study group within one year (seropositive control: odds ratio (OR) = 0.3, 95% confidence interval (CI) 0.2-0.5, p < 0.0001; seronegative control: OR = 0.4, 95% CI 0.2-0.6, p < 0.0001). ACS was more likely to occur in the study group, with the incidence of 7.7% compared to 4.7% (p < 0.0001) in the seropositive control and 1.9% (p <0.0001) in the seronegative control. Adjusting for age and gender, the seronegative control was less likely to develop ACS than the study group within one year (OR = 0.4, 95% CI 0.2-0.7, p = 0.003).Conclusions: This retrospective study demonstrates that CMV infection may be a significant risk factor for VTE and ACS.

Associations of Cytomegalovirus and Muscle Weakness in Older Adults: Results from the Health and Retirement Study

Muscle weakness, measured by grip strength, is associated with disability, physical functioning and mortality; however, the sociobiologic underpinnings of muscle weakness are poorly understood. Immune response to cytomegalovirus (CMV), as measured by immunoglobulin G (IgG) antibody levels, is often used as a marker of immunosenescence with higher antibody levels suggesting accelerated immunosenescence. Previous research has shown immune response to CMV across the life course is socially patterned with disadvantaged groups having higher antibody levels across the life course. Thus, the primary objective of this study was to examine associations between CMV IgG antibodies and grip strength in a nationally representative cohort of older adults, and the role of social factors in these associations. Using data from the Health and Retirement Study (N= 4,251; Mean Age= 67.4 years), we employed gender-stratified weighted linear regression models to estimate the mean difference in grip strength associated with tertiles of CMV IgG response controlling for age, race/ethnicity (White, Black and Hispanic) and educational attainment. For men, higher IgG antibody levels were associated with decreased mean grip strength. For example, men in the highest level of IgG antibody had a grip strength of 37.67 kg (95% CI: 36.30, 39.05) compared to men seronegative to CMV with a grip strength of 38.96 kg (95% CI: 38.18, 39.74). For women, there was little difference in grip strength by CMV IgG response. Our findings suggest accelerated immunosenescence may be an important predictor of reduced grip strength in older adults, and critical to understanding social disparities in grip strength.

Cytomegalovirus and systemic inflammation at time of surgery is associated with worse outcomes in serous ovarian cancer

Objectives: Cytomegalovirus (CMV) is a common infection that establishes latency in healthy people. CMV has been associated with alterations of the immune compartment leading to improved responses, while inflammation has been shown to adversely impact outcomes. We investigated whether CMV serostatus predicts outcomes in ovarian cancer in the presence or absence of inflammation.Methods: A total of 106 patients with serous ovarian cancer from 2006 to 2009 were analyzed. CMV and systemic inflammation was measured using CMV immunoglobulin G (IgG) and C-reactive protein (CRP), respectively, in serum collected prior to cytoreduction. Patients were stratified by CMV IgG (non-reactive, reactive/borderline) and CRP (≤10, >10 mg/L) status. Overall survival (OS) and recurrence-free survival (RFS) were compared by group using log-rank tests and Cox proportional hazards regression models adjusting for age at surgery.Results: Of 106 eligible patients, 40 (37.7%) were CMV+/CRP+, 24 (22.6%) CMV+/CRP-, 19 (17.9%) CMV−/CRP+, and 23 (21.7%) CMV−/CRP−. CRP+ had higher CA-125 levels (P = 0.05) and higher rates of suboptimal debulking (P = 0.03). There were no other significant differences in demographic, surgical, or pathologic factors between groups. CMV+/CRP+ patients median RFS and OS were 16.9 months (95% CI: 9.0–21.1) and 31.7 months (95% CI: 25.0–48.7), respectively, with a significantly worse RFS (aHR: 1.85, 95% CI: 1.05–3.24, P = 0.03) and OS (aHR: 2.12, 95% CI: 1.17–3.82, P = 0.01) compared to CMV−/CRP− (RFS = 31.2 months (95% CI: 16.0–56.4) and OS = 63.8 months (95% CI: 50.7–87.0)). CMV+/CRP− group displayed the longest OS (89.3 months).Conclusions: Previous exposure to CMV and high CRP at surgery portended worse RFS and OS compared to women who tested negative. The CMV+/CRP− group had the longest OS, indicating that CMV status alone, in the absence of inflammation, may be protective.

Seroepidemiology of TORCH antibodies in the reproductive-aged women in China

TORCH, the acronym of Toxoplasma gondii (TOX), others, rubella virus (RUV), cytomegalovirus (CMV) and herpes simplex virus (HSV), is a major contributor to congenital infection. National population-based study on the seroepidemiology of TORCH in women is yet lacking, and it is still obscure whether TORCH infection in the women was associated with adverse pregnancy outcomes. A total of 48,406 asymptomatic women from eight hospitals in China which covered the most areas of mainland China were enrolled in this study, and 26,400 were simultaneously subjected to 7 detection tests for TORCH specific antibodies. Chemiluminescent immunoassay was performed to detect TORCH Immunoglobulin M (IgM) and/or Immunoglobulin G (IgG) antibodies, and IgG avidities of TOX and CMV IgM and IgG positive serum samples. The overall IgG prevalence of TOX, RUV, CMV and HSV-(1 + 2) in the reproductive-aged women was 1.71 %, 81.97 %, 95.09 % and 90.15 % respectively. The corresponding IgM prevalence of TOX, RUV and CMV was 0.30 %, 0.89 % and 0.52 %. Moreover, the rates of primary TOX and CMV infections were at least 0.08 % (21/26,400) and 0.03 % (7/26,400) in the studied population. The distributions of TORCH positive women in various age, season and region groups were different (P < 0.05). The CMV IgM-positive rate was higher in the pregnant women than those in non-pregnant women (P < 0.05). The higher past infection rates of RUV, CMV and HSV in women with bad obstetric history (BOH) imply that TORCH infections are associated with BOH. These data suggest that TORCH infections in the prenatal women, especially with BOH, are worthwhile to be screened by detections of specific IgG and IgM antibodies, and even IgG avidities.

Life Course Socioeconomic Disadvantage and the Aging Immune System: Findings From the Health and Retirement Study.

Previous research has documented a consistent association between current socioeconomic status (SES) and cytomegalovirus (CMV). Early life is likely a critical period for CMV exposure and immune development, but less is known about early-life socioeconomic factors and CMV, particularly in older age populations. Using data from the Health and Retirement Study, we investigated the association between life course socioeconomic disadvantage and immune response to CMV among older adults. Using ordered logit models, we estimated associations between several measures of socioeconomic disadvantage and the odds of being in a higher CMV Immunoglobulin G (IgG) response category in a sample of 8,168 respondents aged older than 50 years. We found a significant association between educational attainment and CMV IgG response. Those with less than a high school education had 2.00 (95% confidence interval [CI]: 1.67-2.40) times the odds of being in a higher CMV category compared to those with a college degree or greater. In addition, we also observed a significant association with parental education and CMV response. Individuals with parents having 8 years or less of schooling had 2.32 (95% CI: 2.00-2.70) times the odds of higher CMV response compared to those whose parents had greater than high school education. CMV IgG levels in older adults are associated with both early-life and adult SES. Life course socioeconomic disadvantage may contribute to disparities in immunological aging.

Cytomegalovirus seroprevalence, recurrence, and antibody levels: Associations with cadmium and lead exposures in the general United States population.

The ubiquitous metals cadmium and lead are immunotoxic, but little is known about their relations to cytomegalovirus (CMV), a widespread herpesvirus. Although CMV infections are mostly asymptomatic, congenital infections are a leading cause of birth defects. In otherwise healthy individuals, there is also some evidence linking subclinical reactivations to accelerated age-related declines in immune function and chronic disease. Our objective was to evaluate associations of blood cadmium and lead biomarkers with CMV infection in a representative sample of the United States population. In seropositive individuals, we also examined associations with CMV-specific immunoglobulin G (IgG) antibody levels and suspected CMV recurrences. Using cross-sectional data from the 1999-2004 National Health and Nutrition Examination Surveys, we fit multivariable survey-weighted regression models accounting for potential confounding by sociodemographic and lifestyle factors and stratifying by age group to allow for heterogeneity. CMV recurrences were defined according to (1) the presence of either CMV-specific immunoglobulin M in sera or CMV viral DNA in urine, and (2) high CMV-specific IgG avidity. We observed null associations for blood cadmium. Increasing blood lead quartiles were related to CMV seropositivity and higher CMV IgG levels (both P trend < 0.01), but not CMV recurrence, only among individuals who were 20-29 years of age. Blood cadmium levels do not appear to be related to immunological markers of CMV infections. The possibility that lead exposures increase the risk of CMV infection and impair immune control of the virus in young adults was suggested. Prospective studies are needed to confirm.

Regional differences in the association of cytomegalovirus seropositivity and multiple sclerosis: A systematic review and meta-analysis

BackgroundDespite of a few decades of investigations, the association and role of cytomegalovirus (CMV) and multiple sclerosis (MS) remain inconclusive. Herein, we performed a meta-analysis to investigate the association between CMV IgG serostatus and MS. MethodsA literature search was conducted on MEDLINE, EMBASE, and Cochrane databases. Eligibility criteria included observational studies assessing the seroprevalence of CMV immunoglobulin G (IgG) in adults with MS and non-MS control. Two authors screened all resulting studies and evaluated the quality of the included studies. Pooled odd ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random-effect model. ResultsThe search identified 771 unique citations, and 15 (3,591 MS patients and 4,241 controls) satisfied eligibility criteria. The meta-analysis of all included studies showed no significant association between CMV IgG seropositivity and MS with a substantial heterogeneity (OR 1.190; 95%CI 0.780–1.813; I2 32.7%). Subgroup analysis, stratified by geographic area, showed different associations and less heterogeneity in each geographical area. In Europe, CMV IgG seroprevalence was lower among people with MS than controls (OR 0.750; 95%CI 0.599–0.940; I213.9%). In contrast, CMV IgG seropositivity was more common among MS patients compared to controls in the Middle East region (OR 5.089; 95%CI 01.067–24.263; I2 5.6%). There was no significant association in North America. ConclusionsThere is evidence of the regional differences in the association between CMV IgG seropositivity and MS. Further biological and epidemiological studies are needed to identify the genetic or environmental factors which are potentially the effect modifiers of this association.