Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Role for APRIL in the Development of SLE- and RA-Associated Lymphomas?
Lundberg1, Ingrid E., Lofstrom2, Björn, Backlin3, Carin, Sundstrom3, Christer, Pettersson4, Tom, Ekbom5, Anders, Baecklund6, Eva
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden,
Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden,
Uppsala University, Sweden,
Helsinki University Hospital, Helsinki, Finland,
Karolinska Institutet, Stockholm, Sweden,
Rheumatology clinic, Uppsala, Sweden
Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are associated with an increased lymphoma risk, in particular diffuse large B cell lymphoma (DLBCL). Involved biologic mechanisms are still unknown. A PRoliferating-Inducing Ligand (APRIL), a cytokine of the TNF superfamily, regulates B-cell activation and survival. It is overexpressed both in lymphomas like DLBCLs and in RA/SLE-patients. We hypothesise that APRIL may have a role in the development of DLBCL in RA and SLE.Investigate APRIL expression in lymphoma tissue from RA/SLE patients with DLBCLs using general population DLBCLs as controls and correlate to clinical characteristics.
Linked, previously presented, registry studies of the Swedish Hospital Discharge Register and the Swedish Cancer Register between 1964 and 1995 yielded 98 patients with RA and 13 with SLE who developed DLBCL. (One SLE-DLBCL Helsinki patient also included). Diagnoses were verified using current ACR criteria for RA and SLE and the WHO classification of lymphoma. General DLBCL patients from Uppsala Region without chronic inflammatory disease were used as controls (n=63). Lymphoma specimens were sectioned and stained with Aprily-2 (Alexis). Percentage APRIL positive staining lymphoma cells were counted in light microscope. The results of the controls were divided in quartiles and the result of the RA/SLE lymphomas compared to the controls using the c2test. Cumulated disease activity (from clinical data abstraction) in RA was scored and measured as area under the curve (AUC).
Mean percentage of stained cells in SLE-, RA- and control-DLBCLs was 25, 11 and 12%. The quartile distribution of the stainings was significantly different in RA DLBCLs (45,14,11,28) and SLE DLBCLs (1,0,0,13) compared to controls. In RA, an association was seen between high cumulated disease activity and high % APRIL positive cells (mean AUC in quartile 1= 636, quartile 4=968).
Our data reflect the heterogeneity of the DLBCL subtype and suggest that APRIL could be of particular importance in the development of lymphoma in SLE and in development of lymphoma in a subset of RA patients with high cumulated disease activity.
To cite this abstract, please use the following information:
Lundberg, Ingrid E., Lofstrom, Björn, Backlin, Carin, Sundstrom, Christer, Pettersson, Tom, Ekbom, Anders, et al; A Role for APRIL in the Development of SLE- and RA-Associated Lymphomas? [abstract]. Arthritis Rheum 2009;60 Suppl 10 :937