Subclinical activation of latent cytomegalovirus (CMV) infection and anti-CMV immune response in patients with atopic dermatitis

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Abstract
Summary Background Microbiological infections are considered to be of pathophysiological importance in atopic dermatitis (AD). As yet, no information is available regarding cytomegalovirus (CMV) infection in this disease. This, however, is of interest because of the high prevalence of latent infections in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. Objectives To investigate the prevalence of latent CMV infection, the frequency of active CMV infection, and the immune response to CMV in patients with moderate to severe AD. Methods To detect active infection we analysed CMV antigen expression by peripheral blood mononuclear cells (PBMC) from 27 patients with moderate to severe AD in comparison with 53 healthy volunteers. We used three monoclonal antibodies recognizing different CMV‐encoded antigens and immunocytological staining (alkaline phosphatase–antialkaline phosphatase technique). Results Patients with AD had a higher mean frequency of CMV‐positive PBMC: 2·25 per 10 000 vs. 0·74 per 10 000 in controls (P = 0·001) as well as a higher incidence of CMV antigenaemia: 29·6% vs. 7·5% (P < 0·01). Seropositivity for anti‐CMV IgG antibodies indicated subclinical activation of latent infection. Remarkably, a clearance of CMV antigenaemia was observed during anti‐eczematous treatment. Significantly higher plasma levels of tumour necrosis factor‐α, which is involved in CMV reactivation, and interleukin‐12, which is crucial for an antiviral cellular immune response, were observed in AD patients in comparison with healthy volunteers. Furthermore, a significantly enhanced frequency of circulating activated HLA‐DR+ T cells especially in CMV‐seropositive AD patients (19·3% vs. 13·5% in seronegative AD patients vs. 10·2% in controls) suggested that the active CMV infection triggers a cellular immune response. This was also supported by a high frequency of CMV‐specific interferon‐γ‐producing T cells in CMV‐seropositive patients with AD. Conclusions Our data suggest that active, subclinical CMV infection is more frequent in patients with moderate to severe AD and may have immunopathophysiological relevance.