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G61(P) New mechanisms of formation of a generalised cytomegalovirus infection in newborns
  1. AY Levkovich,
  2. AA Afonin,
  3. MA Levkovich,
  4. LV Kravchenko
  1. Rostov Scientific-Research Institute of Obstetrics and Pediatrics, Rostov-on-Don, Russia

Abstract

Aims Identifying the role of innate immunity factors in the formation of generalised intrauterine cytomegalovirus infection (CMVI) in newborn infants.

Methods 47 children (group I) had a severe form of generalised CMVI. The control group consisted of 26 clinically healthy children. The diagnosis of intrauterine CMVI was made based on the clinical picture of the disease, detection of CMV DNA in the blood and in the urine, increasing titers of specific IgG to CMV dynamics, detection of IgM in the serum of the child. Determination of expression of TLR-2(CD14+CD282+) and TLR-6(CD14+CD286) on the monocytes was performed by laser flow cytofluorimeter (Beckman Coulter, USA). Polymorphism allelic variants of TLR genes and the viral load was studied using PCR test systems for molecular genetic analysis, developed by GosNIIgenetika (Russia).

Results The clinical picture in severe generalised CMVI was characterised by meningoencephalitis (12,8%), haemorrhagic syndrome (46,8%), malnutrition (38,3%), pneumonia (51,1%), syndrome of oppression of the nervous system (63,8%), convulsive syndrome (51,1%), hepatomegaly (59,5%), presence of fever (38,3%), lymphadenitis (25,2%). In the I group compared with the control group showed a reduction in expression of TLR-2 (CD14+CD282+) monocytes (43,8 ± 8,3%, compared with 76,2 ± 5,6%, p < 0.05). An inverse correlation with viral load (r = 0,81, p < 0,05). Similar changes have been observed for TLR-6 (CD14+CD286+): significantly lower values of expression of TLR-6 was determined in group I (44,6 ± 5,9%) compared to control (61,1 ± 1,4%, p < 0.05). Investigated the frequency of polymorphisms in TLR genes have established that neonates of group I compared with control group, the genotype frequency of Ser/Pro was significantly higher (68,1% and 11,5%, respectively, p < 0,05), and genotype Pro/Pro was significantly lower (25,5% and 80,8% respectively, p < 0,05). Thus, allelic variants of the gene TLR-6 points Ser249Pro polymorphisms may be genetic markers for the development of a severe form generalised CMVI, and genotype Pro/Pro is protective against the severity of CMVI generalised.

Conclusions In children with generalised fetal CMV infection is a decrease in expression of TLR-2 and TLR-6 on monocytes, identified allelic polymorphism of TLR-6 points Ser249Pro. The peculiarities of factors of innate immunity explain the high sensitivity of newborns for CMVI and confirmed their role in shaping the clinical picture of the disease.

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