Previous studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the pathogenesis of EBV+ HL by precluding efficient immune responses. We genotyped exons 2 and 3, encoding the peptide-binding groove of HLA-A, for 32 single nucleotide polymorphisms in 70 patients with EBV+ HL, 31 patients with EBV- HL, and 59 control participants....

Purpose The neoplastic Hodgkin Reed-Sternberg ( HRS) cells in classical Hodgkin’s lymphoma ( cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown. Patients and Methods Immunohistochemistry results for HLA class II were evaluated in 292 primary cHL patients in a population-based approach. Patients were diagnosed between 1989 and 2000 in the northern part of the Netherlands. Median age at diagnosis was 38 years ( range, 8 to 88 years); 63% had Ann Arbor stage I or II,...

To identify genes involved in the pathogenesis of classical Hodgkin lymphoma (cHL), we performed serial analysis of gene expression (SAGE) and array-based comparative genomic hybridization (aCGH). Comparison of SAGE libraries of cHL cell lines L428 and L1236 with that of germinal centre B cells revealed consistent overexpression of only 14 genes. In contrast, 141 genes were downregulated in both cHL cell lines, including many B cell and HLA genes. aCGH revealed gain of 2p, 7p, 9p, 11q and Xq and loss of 4q and 11q. Eighteen percent of...

Classical HL is a hematological malignancy in which immunological interactions are crucially involved. The neoplastic HRS cells use a variety of strategies to evade immune reactions, but also shape the immune response to their own benefit. Antigen presentation may be involved in both of these mechanisms. The significance of antigen presentation is supported by an inherited susceptibility to cHL that has been associated with HLA class I and HLA class II alleles and haplotypes (the sequence of alleles on one chromosome; chapter 2). Because antigenic peptides derived from...

Various studies have indicated that the human leukocyte antigen (HLA) region is associated with Hodgkin’s lymphoma. We recently showed a specific association of the HLA class I region with EBV-positive Hodgkin’s lymphoma cases. One haplotype of two consecutive microsatellite markers (D6S265 and D6S510) was overrepresented in the patient group, whereas another haplotype was underrepresented. Here, we did fine mapping of this region of -400 kb as a next step to find the causative single-nucleotide polymorphism(s) (SNP). To select candidate SNPs for screening the total study population, several known...