The major finding was a bimodal incidence pattern with an increased risk of lymphoma, mainly NHL, early during follow-up, but lung cancer and squamous skin cancer later on.

NHL in this national SLE cohort was predominated by the aggressive DLBCL subtype. The prognosis of NHL was comparable with that of the general lymphoma population. There were no indications of treatment-induced lymphomas. Molecular subtyping could be a helpful tool to predict prognosis also in SLE patients with DLBCL.

Low-dose chemotherapy was not a major cause of myeloid malignancy in our population-based cohort of SLE patients nor in the reported cases from literature. Leucopenia was a risk factor for myeloid leukaemia development and an MDS was frequently seen. Therefore bone marrow investigation should be considered in SLE patients with long-standing leucopenia and anaemia.

Objective TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B‐cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. Materials and methods TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)‐like regimen, 76 CHOP‐treated and 196 rituximab‐CHOP‐treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with 3H‐thymidine incorporation and propidium iodine staining. Results TRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression‐free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes in vitro. Conclusions We show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.

The high expression of APRIL in DLBCL in SLE and in an RA subset might indicate an association between APRIL and lymphoma in these subsets of rheumatic diseases, but could also reflect a dysregulation of APRIL per se in these patient groups.

No abstract

We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2. Genes and Immunity (2000) 1, 380-385.

Background and ObjectivesThe risk for lymphoma is increased in many rheumatic conditions. Diffuse Large B-cell Lymphoma (DLBCL) is a common, yet heterogeneous lymphoma subtype and good prognostic biomarkers are warranted. We have previously shown that the rheumatic autoantigen Ro52 is expressed predominantly in leukocytes and that over expression affects lymphocyte proliferation. Further, the Ro52 (Trim21) gene maps to a tumour suppressor locus. We therefore hypothesised that Ro52 expression might be used as a prognostic marker for lymphoma. Materials and Methods Proliferation of in vitro stimulated lymphocytes was determined by thymidine incorporation and cell cycle analysis and compared to Ro52 mRNA levels. Three cohorts of patients with DLBCL were investigated for Ro52 expression by immunohistochemistry using monoclonal Ro52 antibodies. The first cohort consisted of patients with rheumatic disease treated with cytostatic drugs only (n = 43). The two others were nonrheumatic patients treated with anthracycline-based (CHOP) therapy alone (n = 74), and with the addition of Rituximab (n = 196). Results A robust inverse correlation between Ro52 expression levels and cellular proliferation was observed (r 2 = 0.50, p < 0.0001). Confirming this biological phenomenon, low expression of Ro52 in lymphoma tissue was significantly correlated to overall survival (p < 0.0001), as well as progression-free survival (p < 0.0001) in patients with DLBCL treated with CHOP therapy alone. This was further confirmed in the Rituximab-CHOP treated cohort, with a significantly lower overall survival (p < 0.0001) and progression-free survival (p = 0.0005). The association was independent of Ann Arbor classification and DLBCL subtype, emphasising that Ro52 expression is a parameter of added value in lymphoma investigations to understand the patient prognosis. Conclusions Our data demonstrate that low Ro52 expression is associated with more aggressive lymphomas. Further, our data functionally link low Ro52 expression with increased cellular proliferation. Ro52 may thus constitute a novel biologically relevant biomarker predicting patient survival in lymphoma. SEMAPHORIN3A IS A POTENT B CELL REGULATORY MOLECULE IN SLE