R. Schuurman

Adenovirus DNA Positivity in Nasopharyngeal Aspirate Preceding Hematopoietic Stem Cell Transplantation: A Very Strong Risk Factor for Adenovirus DNAemia in Pediatric Patients

Human adenovirus (HAdV)-positive nasopharyngeal aspirate preceding hematopoietic stem cell transplantation was prospectively analyzed in 62 patients. By multivariate Cox proportional hazard models, HAdV-positive nasopharyngeal aspirate was the only predictor for HAdV DNAemia after hematopoietic stem cell transplantation (P < .001). HAdV DNAemia was a predictor for alloreactive disease. Early detection and intervention might help to prevent HAdV disease after hematopoietic stem cell transplantation.

Influence of Donor Cytomegalovirus (CMV) Status on Severity of Viral Reactivation after Allogeneic Stem Cell Transplantation in CMV-Seropositive Recipients

We investigated the role of donor cytomegalovirus (CMV) serostatus on reactivation of CMV infection in CMV-infected transplant recipients. Reactivation of CMV infection occurred more frequently in patients receiving a CMV-positive graft but was less severe than in patients receiving a CMV-negative graft. These data suggest roles for both virus as well as CMV-specific immunity present in the graft.

Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT

Hematopoietic SCT (HSCT) is often complicated by viral reactivations. In this retrospective cohort study (January 2004–August 2008), predictors for human herpes virus 6 (HHV6)-reactivation and associations between HHV6-reactivation and clinical outcomes after allogeneic HSCT were studied. HHV6 DNA load in plasma was monitored weekly by quantitative real-time PCR. Associations between the main end point HHV6-reactivation and other end points, that is, acute GVHD (aGVHD) and NRM were analyzed using Cox proportional hazard models. In total, 108 patients receiving either a myeloablative (MA; n=60) or non-myeloablative (NMA; n=48) conditioning regimen were included. Median age was 40 years (range 17–65); median follow-up was 20 months (range 3–36). In 16/60 (27%) patients with MA conditioning regimen, a HHV6 reactivation was observed (mean viral load 50u2009323u2009cp/mL) compared with 2/48 (4%) patients with a NMA conditioning regimen with low viral load (mean 1100u2009cp/mL). In multivariate analysis, MA conditioning was the only predictor for HHV6 reactivation (P=0.02). In addition, HHV6 reactivation was associated with grades 2–4 aGVHD (P<0.001) and NRM (P=0.03). Regular monitoring of HHV6 reactivation after HSCT might be important in MA HSCT patients to enable early initiation of antiviral treatment or to anticipate aGVHD, all of which may improve clinical outcome.

T-cell response to viral antigens in adults and children with common variable immunodeficiency and specific antibody deficiency.

Several T cell abnormalities have been described in common variable immunodeficiency (CVID), a B cell disorder of mainly unknown origin. A subset of CVID patients suffers from frequent reactivations of herpes viruses. We studied T cell function in CVID [and in a subset of paediatric patients with specific antibody deficiency (SAD)] by measuring T cell proliferation and cytokine production in response to herpes virus‐antigens in paediatric CVID patients (nu2003=u20039) and paediatric SAD patients (nu2003=u20035), in adult CVID patients (nu2003=u200314) and in healthy controls. Paediatric CVID patients, but not SAD patients, displayed moderately increased CD8+ T cell proliferation in response to cytomegalovirus, human herpes virus type 6B (HHV6‐B) and herpes simplex virus compared to controls. CD8+ T cell responses in adult CVID patients tended to be increased in response to cytomegalovirus and herpes simplex virus. In response to stimulation with herpes virus antigens, the proinflammatory cytokines interleukin (IL)‐1β, IL‐6, tumour necrosis factor (TNF)‐α and interferon inducible protein (IP)‐10 were produced. Overall, no major differences were detected in cytokine production upon stimulation between patients and controls, although higher IL‐10 and IL‐12 production was detected in paediatric patients. In conclusion, cellular immunity against herpes virus antigens appears undisturbed in CVID patients, although defects in subpopulations of CVID patients cannot be excluded.