Long-lasting chronic high load carriage of Epstein-Barr virus is more common in young pediatric renal transplant recipients.

BACKGROUND: Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation. METHODS: A retrospective study of 58 children aged 1-17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA ≥ 4.2 log10 Geq/ml in > 50% of the samples during ≥ 6 months. RESULTS: At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5-6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7-13). CONCLUSIONS: CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

Long-term study showed that vaccination protected paediatric renal transplant recipients from life-threatening varicella zoster virus.

AIM: Renal transplant patients are particularly susceptible to highly contagious diseases due to their reduced immunity. We studied transplant recipients to gauge their varicella zoster virus (VZV) serology status over time and the outcome of any VZV infections. METHOD: This retrospective study comprised 85 children who underwent renal transplants in Gothenburg, Sweden, from 1986 to 2014, at a mean age of eight (1-18) years. The children's medical records were reviewed and 47 had the VZV infection pre-transplant and 38 had been vaccinated pre-transplant. Clinical outcomes were available for 85 children and serology results for 72. RESULTS: At transplantation, the VZV seropositivity rate was 50% in the vaccination group and 94% in the infection group and the antibody titres were significantly lower in the vaccination group (p = 0.031). During the median follow-up period of five years post-transplant, 28% of the vaccinated children and 97% of the infection group remained seropositive and the varicella infection affected eight children: one in the infection group and seven in the vaccination group. The herpes zoster was observed in two children in the infection group. CONCLUSION: This study demonstrated that VZV vaccination protected from symptomatic infections to a lesser extent than natural infection, but provided effective protection from life-threatening disease.

ß-catenin Helices in the cytoplasm of sporadic and FAP duodenal adenomas.

BACKGROUND: Initiation and progression in conventional adenomas is triggered by deregulation of Wnt/ß-catenin signaling. In the absence of Wnt signal (off-state), ß-catenin prevents phosphorylation of glycogen synthase kinase (GSK)-3ß leading to aberrant nuclear accumulation in human tumors. While investigating the nuclear expression of ß-catenin in biopsies from duodenal adenomas, we observed a non-previously reported phenomenon, namely the presence of ß-catenin cytoplasmic helices (coils). MATERIALS AND METHODS: Sections from 39 biopsies were immunostained with ß-catenin: 25 from duodenal adenomas and the remaining 14 had normal duodenal mucosa (n=11) or polypoid gastric duodenal metaplasia (n=3). RESULTS: Eighteen out of the 25 duodenal adenomas (72%) showed ß-catenin helices; in contrast, none of the 33 control biopsies (including those with normal duodenal mucosa, gastric duodenal metaplasia and normal mucosa adjacent to 19 adenomas) showed ß-catenin helices (p<0.05). The review of diagnostic H&E-stained sections and of ß-catenin-stained nuclei revealed that the dysplastic nuclei were arranged in a picket fence-like fashion along the basement membrane of the glands and not as loops within the dysplastic glands; the nuclei of the dysplastic glands were not forming part of the ß-catenin helices. DISCUSSION: If these ß-catenin coils are unrelated to an abnormal nuclear distribution at the base of the dysplastic glands, the rational explanation might be that the helices highlight changes taking place in the cytoplasm of affected glandular cells. CONCLUSION: According to some authors, mutations in the ß-catenin genes are always associated with a morphologically neoplastic course. It is herein proposed that ß-catenin helices in duodenal adenomas might uncover a novel cytoplasmic phenomenon ensuing during the adenoma-carcinoma pathway.

ß-catenin helices in the cytoplasm of sessile serrated adenoma/polyps and conventional colorectal adenomas.

Initiation and progression in conventional adenomas is triggered by deregulation of WNT/ß-catenin signaling. In the absence of WNT signal (off-state), ß-catenin prevents phosphorylation of GSK3ß, leading to aberrant nuclear accumulation in human tumors. It has been postulated that mutations in the ß-catenin gene are always associated with a morphologically-neoplastic course. While investigating the nuclear expression of ß-catenin in 170 colorectal biopsies, we observed a non-previously reported phenomenon, namely the presence of ß-catenin cytoplasmic helices in 29% (n=7) of 24 sessile serrated adenoma/polyps (SSA/P), in 24% (n=13) of 54 adenomas, in 8% (n=3) of 38 specimens with IBD, but in none (0/54) with normal mucosa. The earliest ß-catenin helices were found at the bottom of SSA/P glands (the domain of stem cells in the colorectal mucosa). It is submitted that ß-catenin helices might highlight a non-previously described cytoplasmic phenomenon evolving during the serrated-carcinoma pathway in SSA/P, and during the adenoma-carcinoma pathway in conventional adenomas.

Human herpesvirus type 6 DNAemia and infection following allogeneic stem cell transplantation with a focus on long-term outcome.

Cases of human herpesvirus type 6 (HHV-6) infection and disease were retrospectively analysed in a cohort of 97 allogeneic haematopoietic stem cell transplantation (allo-SCT) patients in Gothenburg, Sweden (1997-2001). Altogether 54 of 97 (56%) patients were tested for HHV-6. HHV-6 DNAemia was detected in 15 of the tested patients at a median of 76 (range 24-387) days after SCT. Nine of these patients were treated against HHV-6 infection and disease for a total of 11 treatment episodes. The morbidity associated with HHV-6 DNAemia following allo-SCT was in most cases moderate. The overall 1-y survival among the patients with HHV-6 DNAemia was 11/15 (73%) and the 5-y survival was 10/15 (67%), which was not significantly different from the whole cohort.

Cytomegalovirus DNAemia and treatment following allogeneic stem cell transplantation with a focus on long-term outcome.

Cytomegalovirus (CMV) is an important factor for morbidity and long-term outcome after allogeneic haematopoetic stem cell transplantation (allo-SCT). Cases of proven and probable CMV infection and disease among 97 allo-SCT recipients in Gothenburg, Sweden, 1997-2001, were analysed. CMV DNAemia was detected in 60 patients at a median of 30 days after SCT. Four patients (4%) had CMV disease; 2 had proven and 2 had probable CMV disease. Of these 4 patients, 1 died of CMV disease. In 1 additional patient, CMV was considered to have contributed to the patient's death. Fifty patients (51%) were treated in a total of 93 treatment episodes. The overall 1-y survival was 75% and the 5-y survival 55%. Patients with diagnosed CMV DNAemia had improved survival. No significant differences in survival rates were seen between the donor/recipient serological groups. An increased risk of CMV DNAemia was seen after SCT with a seronegative donor to a seropositive recipient. CMV disease with debut more than 110 days after transplantation was related to steroid treatment for graft-versus-host disease. The morbidity related to CMV disease following allo-SCT was low over the past 10 y, probably due to CMV surveillance and early treatment.