Clear recommendations for the management of acute varicella-zoster virus (VZV) infections for cases of significant exposure and the use of prophylactic drugs after solid-organ transplantation are missing due to the lack of evidence by prospective studies. Heterogeneity in patient groups, patient numbers, age groups, immunosuppressive regimens, timing, and dosage of aciclovir and/or varicella-zoster immunoglobulin (VZIG), pre-transplant vaccination or VZV wild-type infection and inconsistency of data make comparability of different studies impossible. Although the benefit of aciclovir and/or VZIG is uncertain in immunosuppressed children, prospective controlled double-blind studies are not feasible for ethical considerations as fatal cases with disseminating varicella disease are well known in these patient groups despite the use of aciclovir and/or VZIG, whereas severe side-effects of these drugs are rare. However, a reporting bias is likely as mainly severe or fatal cases might have been predominantly published or cases of successfully used aciclovir and/or VZIG in mild cases or in cases of breakthrough infections after vaccination. As neither VZIG prophylaxis nor treatment with intravenous aciclovir offers complete protection against severe VZV infection to immunosuppressed pediatric solid-organ transplant recipients, high priority should be given to vaccination against VZV prior to transplantation, and, most importantly, in their close contact persons. Clinical observations suggest that only assessment of humoral immunity together with cellular immunity may allow predication about protection in exposed patients.
BackgroundAlterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto’s thyroiditis (HT, n = 18) and healthy controls (HC, n = 70).MethodsProportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization.ResultsOur results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC.ConclusionsPatients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for treatment of HT and associated autoimmune diseases.
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