A clinical study of lyophilized intravenous human immunoglobulin containing high-titer cytomegalovirus-neutralizing antibody for the treatment of cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection increases the risk of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, some patients do not respond to ganciclovir (GCV) or foscarnet sodium. Lyophilized intravenous human immunoglobulin containing high-titer CMV-neutralizing antibody (CMV-IVIG) is another option to further improve treatment safety and efficacy. This study was designed to evaluate the efficacy of the combination of CMV-IVIG with traditional antiviral drugs (GCV or foscarnet sodium) at different time points for the treatment of post-allo-HSCT CMV viremia and to determine the clinical value of CMV-IVIG as a preemptive treatment strategy. METHODS: The clinical data of 73 patients who received allo-HSCT and concurrent CMV-IVIG to treat post-allo-HSCT CMV viremia at our hospital between January and September 2020 were retrospectively analyzed. The patients were divided into two groups based on the total dose of antithymocyte globulin (ATG) used in the pretransplant preconditioning regimen, i.e., the low-dose ATG group (rabbit ATG ≤6 mg/kg, porcine ATG ≤40 mg/kg) (n=19) and the high-dose ATG group (rabbit ATG >6 mg/kg, porcine ATG >40 mg/kg) (n=54). Real-time quantitative polymerase chain reaction (RQ-PCR) was performed to measure the peripheral CMV-DNA level. Patients with CMV viremia (CMV-DNA >1,000 copies/mL) received concurrent CMV-IVIG therapy [early (within 3 days after the diagnosis of CMV viremia) or late (after 3 days)]. The CMV-DNA conversion rate, the median time of CMV-DNA conversion, and the two-week response rate and reactivation rate were analyzed for different ATG doses and different time points of CMV-IVIG use. RESULTS: The overall response rate to CMV-IVIG combined with traditional anti-CMV drugs was 100%. Early use of CMV-IVIG significantly reduced the median time of CMV-DNA conversion (14 vs. 21 days, P=0.000), especially in the high-dose ATG group (14 vs. 23 days, P=0.000). CONCLUSIONS: For patients with post-allo-HSCT CMV viremia, early use of CMV-IVIG effectively accelerates CMV-DNA conversion and peripheral CMV clearance, significantly improves the two-week response rate, and reduces the two-week reactivation rate. These effects are more pronounced in the high-dose ATG group.

Risk of congenital cytomegalovirus infection in children born to women with IgG avidity in the grey zone during first trimester of pregnancy.

INTRODUCTION: Cytomegalovirus (CMV) is the most common congenital viral infection and is regarded as the leading nongenetic cause of sensorineural hearing loss. Currently, international consensuses discourage prenatal screening of pregnant women. However, in few countries mainly in Southern Europe, screening of pregnant women for CMV infection is common practice. Management of women found with IgG+/IgM + and IgG avidity titers in the grey zone during first trimester causes significant stress to both families and health care workers. PATIENTS AND METHODS: Pregnant women referred to our outpatient clinic with the diagnosis of acute CMV infection (IgM+/IgG+) during early pregnancy (gestational age ≤ 14 weeks) and IgG avidity in the grey zone were prospectively followed. The administration of CMV-HIG was offered and follow-up included fetal U/S, amniocentesis for CMV-DNA detection and MRI when appropriate. All neonates were examined by urine PCR and prospectively followed according to existing recommendations. RESULTS: Ninety women (mean age 30.8 years) were retrospectively analyzed. Most (79.6%) received CMV-HIG. Four women terminated pregnancy (2 unrelated to CMV reasons and 2 because of CMV-positive amniotic fluid). Eighty-seven babies were born asymptomatic. Two newborns were diagnosed with congenital CMV infection. The overall transmission rate was 4.4%; 4.3 versus 5.6% for those receiving or not CMV-HIG. No adverse outcomes were detected during follow-up (median 24 months). Maternal age, parity, detection of maternal CMV-viremia upon diagnosis, delay between diagnosis and consultation, gestational week of first consultation, administration of CMV-HIG and number of doses were not associated with the risk of vertical CMV transmission. DISCUSSIONS: Vertical transmission of CMV infection in pregnancies with acute CMV-infection and IgG avidity titers in the grey zone during first trimester was 4.4%, higher than that in infants born post nonprimary infection (NPI) during pregnancy. More powered studies are needed to prove a significant reduction in transmission using CMV-HIG.

Influence of human cytomegalovirus on the expression of natural-killer group 2-members receptors on the natural killer cells / 中华传染病杂志

Objective To examine the effect of human cytomegalovirus (CMV) on the expressions of natural killer group 2 members (NKG2),including natural-killer group 2-member A (NKG2A),natural-killer group 2-member C (NKG2C) and natural-killer group 2 member D (NKG2D) receptors on the natural killer (NK) cells.Methods NK cells were isolated from the peripheral blood mononuclear cells of 20 healthy individuals using EasySep magnetic beads.NK cells and CMV-infected human embryonic lung fibroblast (HELF) were co-cultured for 24 h and regarded as experimental group.While CMV-uninfected NK cells co-cultured with HELF and only NK cells were taken as control groups.Flow cytometry was used to detect the expressions of the NK cell receptors in experimental and control groups.The comparison between groups was done by Wilcoxon rank sum test.Results The percentages of NK cells expressing NKG2C and NKG2D in group of CMV-infected NK cells co-cultured with HELF were 34.26％±7.99％ and 24.94％ ± 5.24％,respectively,which were significantly higher than those in CMVuninfected NK cells co cultured with HELF (26.31％ ±6.41％; Z=-3.285,P=0.001 and 20.02％±6.80％ ; Z=-3.285,P=0.001,respectively) and NK cells alone (25.78％± 6.62％ ; Z=-3.211,P=0.001 and 20.12 ％ ± 6.75 ％ ; Z=-3.285,P =0.001,respectively),while no significant changes were found in the expressions of the two receptors between groups of CMV-uninfected NK cells co-cultured with HELF and NK cells alone (both P＞0.05).Moreover,no significant changes were found in the expression of NKG2A among groups (all P＞0.05).The levels of NKG2A+ NKG2C,NKG2A+NKG2D,NKG2C+ NKG2A-and NKG2D+ NKG2A-cells in CMV infected NK cells co-cultured with HELFgroup were 2.99％ ±2.62％,6.13％±2.44％,26.62％ ±7.63％ and 20.44％±5.68％,respectively,while those in group of CMV-uninfected NK cells co-cultured with HELF were 4.44％ ± 4.25％ (Z=-2.240,P=0.025),6.99％±2.33％ (Z=-2.053,P=0.040),19.52％±6.80％ (Z=-2.800,P=0.005) and 15.78％±7.48％ (Z=-2.875,P=0.004),respectively.However,no significant changes were found in the expressions of NKG2A+ NKG2C+ and NKG2A+ NKG2D+ among groups (all P＞0.05).Conclusions CMV infection may change the NK receptor expressions,then stimulatory NKG2C and NKG2D signal transductions are enhanced and the inhibitory NKG2A signal conduction is weakened during CMV infection.

Relationship between Idiopathic Thrombocytopenic Purpura and Human Cytomegalovirus Infection in Infants / 实用儿科临床杂志

Objective To explore the relationship among idiopathic thrombocytopenic purpura(ITP),human cytomegalovirus(HCMV) infection,and immunological function in infants.Methods HCMV-Ab were tested by ELISA;HCMV DNA were tested by PCR for the case groups (n=54) and the controls(n=30).At the same time,T cell subgroups were tested by direct IF staining for the case groups.Results In the case group,the positive infants of HCMV Ab and HCMV-DNA were more than those in the controls(P