TY  - JOUR
A1  - Gerhard‐Hartmann, Elena
A1  - Jöhrens, Korinna
A1  - Schinagl, Lisa‐Marie
A1  - Zamó, Alberto
A1  - Rosenwald, Andreas
A1  - Anagnostopoulos, Ioannis
A1  - Rosenfeldt, Mathias
T1  - Epstein–Barr virus infection patterns in nodular lymphocyte‐predominant Hodgkin lymphoma
JF  - Histopathology
N2  - Aims
To investigate Epstein‐Barr virus (EBV) latency types in 19 cases of EBV‐positive nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL), as such information is currently incomplete.
Methods and results
Immunohistochemistry (IHC) for CD20, CD79a, PAX5, OCT2, CD30, CD15, CD3 and programmed cell death protein 1 was performed. For EBV detection, in‐situ hybridisation (ISH) for EBV‐encoded RNA (EBER) was employed combined with IHC for EBV‐encoded latent membrane protein (LMP)‐1, EBV‐encoded nuclear antigen (EBNA)‐2, and EBV‐encoded BZLF1. In 95% of the cases, neoplastic cells with features of Hodgkin and Reed–Sternberg (HRS) cells were present, mostly showing expression of CD30. In all cases, the B‐cell phenotype was largely intact, and delineation from classic Hodgkin lymphoma (CHL) was further supported by myocyte enhancer factor 2B (MEF2B) detection. All tumour cells were EBER‐positive except in two cases. EBV latency type II was most frequent (89%) and type I was rare. Cases with latency type I were CD30‐negative. Five cases contained some BZLF1‐positive and/or EBNA‐2‐positive bystander lymphocytes.
Conclusions
As HRS morphology of neoplastic cells and CD30 expression are frequent features of EBV‐positive NLPHL, preservation of the B‐cell transcription programme, MEF2B expression combined with NLPHL‐typical architecture and background composition facilitate distinction from CHL. EBER ISH is the method of choice to identify these cases. The majority present with EBV latency type II, and only rare cases present with latency type I, which can be associated with missing CD30 expression. The presence of occasional bystander lymphocytes expressing BZLF1 and/or EBNA‐2 and the partial EBV infection of neoplastic cells in some cases could indicate that EBV is either not primarily involved or is only a transient driver in the pathogenesis of EBV‐positive NLPHL.
KW  - EBV
KW  - Hodgkin lymphoma
KW  - latency type
KW  - NLPHL
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276327
VL  - 80
IS  - 7
SP  - 1071
EP  - 1080
ER  - 
TY  - JOUR
A1  - Ritter, Julia
A1  - Zimmermann, Karin
A1  - Jöhrens, Korinna
A1  - Mende, Stefanie
A1  - Seegebarth, Anke
A1  - Siegmund, Britta
A1  - Hennig, Steffen
A1  - Todorova, Kremena
A1  - Rosenwald, Andreas
A1  - Daum, Severin
A1  - Hummel, Michael
A1  - Schumann, Michael
T1  - T-cell repertoires in refractory coeliac disease
JF  - Gut
N2  - Objective Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. Design DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n= 8), RCD type II (n= 8) and unclassified Marsh I cases (n= 3) collected from 2002 to 2013 was examined by TCR beta-complementarity- determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. Results On average, 106 sequence reads per sample were generated consisting of up to 900 individual TCR beta rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6% of all TCR beta rearrangements, which was significantly higher than in controls (6.8%; p<0.01) or RCD type I (6.7%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliad-independent CDR3 motifs were only detectable at low frequencies. Conclusions TCR beta-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCR beta rearrangements. Dominant TCR beta sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.
KW  - Intestinal Intraepithelial Lymphocy
KW  - Delta Repertoire
KW  - Lymphoma
KW  - Usage
KW  - Clonality
KW  - Sprue
KW  - Chains
KW  - Design
KW  - Epitope
KW  - Frequency
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226350
VL  - 67
IS  - 4
ER  -