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Epstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD) is a heterogeneous and potentially lifethreatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular blood compartments of stem cell transplant (SCT; n = 5), solid organ transplant recipients (SOT; n = 15), and SOT having chronic elevated EBV-DNA load (n = 12). In SCT, EBV DNA was heterogeneously distributed, either in plasma or leukocytes or both. In SOT, EBV DNA load was always cell associated, predominantly in B cells, but occasionally in T cells (CD4 and CD8) or monocytes. All SCT with cell-associated EBV DNA showed BARTs and EBNA1 expression, while LMP1 and LMP2 mRNA was found in 1 and 3 cases, respectively. In SOT, expression of BARTs was detected in all leukocyte samples. LMP2 and EBNA1 mRNA was found in 5/15 and 2/15, respectively, but LMP1 mRNA in only 1, coinciding with severe PTLD and high EBV DNA. Conclusion: EBV DNA is differently distributed between white cells and plasma in SOT versus SCT. EBV RNA profiling in blood is feasible and may have added value for understanding pathogenic virus activity in patients with elevated EBV-DNA. [ABSTRACT FROM AUTHOR]

Summary:An X-linked severe combined immunodeficient (SCID) patient received a nonirradiated erythrocyte transfusion and developed transfusion-associated graft-versus-host disease (TAGVHD), which was controllable with high-dose corticosteroids. Haplo-identical SCT was performed, after a myeloablative conditioning regimen. At day +26, he developed GVHD. Chimerism studies revealed DNA of the erythrocyte transfusion donor (ETD) and recipient only. Because of early nonengraftment and the presence of alloreactive T cells of ETD origin, the patient was treated with an immunosuppressive conditioning regimen followed by a second SCT from the same donor. While tapering immunosuppression, he again developed mild GVHD, and DNA of ETD and bone marrow donor origin were both present. On cyclosporin, the ETD-DNA signal finally disappeared. High-resolution HLA typing revealed haplo-identity between BMD, ETD and the patient, which might have contributed to the relative mild course of the TAGVHD.Bone Marrow Transplantation (2003) 32, 1027-1030. doi:10.1038/sj.bmt.1704266 [ABSTRACT FROM AUTHOR]

Mutations of the Bruton's tyrosine kinase (Btk) gene cause X linked agammaglobulinaemia (XLA). This inherited immunodeficiency disease causes an arrest in B cell differentiation of pre-B cells to mature B cells. In this study we report the characterisation of mutations in the Btk gene in 10 unrelated XLA families. The screening approach we used was based on reverse transcriptase PCR and direct cycle sequencing of the amplified products followed by analysis of the observed mutations at the level of genomic DNA. The single strand confirmation polymorphism (SSCP) technique was used for assessment of the carriers in some of these families. Various mutations throughout the coding gene were observed, including missense and nonsense mutations, a deletion, and several splicing defects. None of the mutations except one has been previously described. There were three point mutations resulting in a single amino acid substitution. One of these missense mutations was observed in a conserved region of the PH domain, the other two were found in the src homology domain 2 that is involved in phosphotyrosyl peptide binding. Two mutations were single base pair substitutions resulting in premature stop codons. In four patients abnormal Btk transcripts were found that were the result of aberrant splicing. One small deletion was observed causing a frameshift and a secondary premature termination signal. Characterisation of the mutations responsible for XLA allowed us to diagnose the disease conclusively and identify the phenotypically normal female carriers. [ABSTRACT FROM PUBLISHER]