HCMV seropositivity is associated with specific proinflammatory immune phenotype in women with implantation failure

HCMV coevolved with humans for millions of years and is now one of the most widespread infections worldwide. For a long time HCMV seropositivity was considered a safe clinical condition. In recent decades both clinical observations and research results indicated that the very presence of HCMV in human organism specifically influences immune system and may affect reproduction as a process greatly dependent on immune cells function. Anti-HCMV IgG, IgG avidity, lymphocyte subsets as well as NK cytotoxicity was investigated in 470 infertile women who were eligible for IVF/ET. 419 patients were IgG anti-HCMV-positive (HCMV-seropositive) and only 51 (10.8 %) were IgG anti- HCMV-negative (HCMV-seronegative). There was not a single case of clinically significant level of low-avidity IgG. HCMV-seropositive patients had significantly increased levels of HLA-DR expression on T-lymphocytes (both on CD3CD8 and especially on CD3CD4 subsets) and HLA-DR expression on NK-lymphocytes (CD56+CD3-), increased levels of NKT-like cells (CD3+CD8+CD56+) but decreased levels of CD8 + NK lymphocytes compared to HCMV-seronegative patients. That difference was caused by significant numbers of individuals with deviated "accentuated" immune phenotypes in HCMV seropositive patients. The latter had increased (>7.5 %) levels of HLA-DR expression on T helpers in 136 cases from 419 (32.4 %) while in HCMV-seronegative group this accentuation was observed only in 3 of 51 patients (5.8 %), (OR -5.9, p < 0.0003). The number of cases with significantly increased CD56 expression on Tc lymphocytes, HLA-DR on NK and decrease of CD8-positive NK cells was more often observed in HCMV-seropositive group compared to seronegative. Thus, possibly HCMV seropositivity specifically influences immune system and results in pro-inflammatory phenotype formation in part of infected population. It was found that accentuations in immune phenotype of HCMV-seropositive women are very similar to previously described in association with reproductive failures but without HCMV serostatus taken into account.