Impact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study.

INTRODUCTION: Although solid organ transplant (SOT) recipients with pretransplant serology for cytomegalovirus (CMV-R+) are considered at intermediate risk for CMV infection post transplantation, CMV infection remains a major cause of morbidity in this population. We prospectively characterized whether having pretransplant CMV-specific cellular immunity is independently associated with controlling infection after transplantation in R + SOT recipients. METHODS: A prospective cohort of consecutive R + SOT recipients that received pre-emptive treatment for CMV infection was monitored after transplantation and variables were recorded during the follow-up. The cytomegalovirus-specific T-cell immune response was characterized by intracellular cytokine staining and viral loads determined using real-time PCR. RESULTS: One hundred and thirty-five R + SOT recipients were included (67 kidney, 64 liver, four liver-kidney). Only one-third of the patients (42; 31.85%) had CMV-specific T-cell immunity (CD8+CD69+INF-γ+ T cells >0.25%) before transplantation. Patients with negative pretransplant immunity had more CMV infection (49, 52.7% vs. 15, 35.7%; p 0.07) and received more antiviral therapy than those with immunity (32, 34.4% vs. 6, 14.3%, p 0.016). Having CMV specific immunity was an independent factor for protection from developing viraemia ≥2000 IU/mL (OR 0.276, 95% CI 0.105-0.725, p < 0.01) and lower administration of treatment (OR 0.398, 95% CI 0.175-0.905, p 0.028). Only patients with no pretransplant CMV-specific T-cell response were diagnosed with CMV-disease (8, 8.6% vs. 0, 0%, p 0.05). DISCUSSION: Our results show that having a pretransplant CMV specific T-cell response may be associated with a lower rate of CMV viraemia and less antiviral treatment after transplantation; however, more prospective studies are needed to confirm these findings.

Microsatellite alterations indicating monoclonality in atypical hyperplasias associated with breast cancer.

One model of breast tumorigenesis postulates a sequential evolution from normal to proliferative epithelium and eventually to neoplasia, but genetic data to support this progression have been limited. We wished to determine whether atypical hyperplasia (AH), a proliferative lesion conventionally classified and treated as benign, but associated with an increased risk of developing carcinoma, might show evidence of genetic abnormalities. Using the polymerase chain reaction (PCR), we examined DNA extracted from 12 separate AH lesions, from six breast cancer patients' paraffin-embedded tissue specimens, for alterations in microsatellite repeat sequences. Five of 12 AH lesions, from three of six patients, demonstrated alterations in microsatellite sequences in patterns indicating that the AH lesions are monoclonal or contain a substantial monoclonal component. We conclude that a subset of AH lesions from patients with breast cancer are characterized by monoclonal microsatellite alterations; therefore, they may already be neoplastic. This finding lends support to one postulated sequence of breast tumorigenesis and suggests that some type of genetic instability may play a role early in breast tumor development.