Systemic lupus erythematosus and B-cell hematologic neoplasm

Abstract

The association of systemic lupus erythematosus (SLE) and B-cell malignancy is widely reported in the literature. Here we report nine cases of concurrent of SLE or discoid lupus erythematosus (DLE) and lymphoma or plasma cell disorder. A MEDLINE search was done using the keywords, 'SLE' and 'lymphoma' and the characteristics of all identified cases were summarized and analyzed, along with data from our own cases. Numerous variants of B-cell malignancies were encountered in these patients. B-cell malignancy occurs after the diagnosis and treatment of SLE in most reported cases, although it may precede SLE, or occur synchronously with it. The age at onset of the B-cell neoplasm in SLE patients is similar to that in the general population. Mortality in patients with both diseases is associated with progressive B-cell neoplasm, sepsis secondary to either disease, or both. B-cell malignancy and SLE seem to run independent clinical courses rather than being affected by each other. The use of immunosuppressive drugs is common in patients with SLE diagnosed prior to B-cell lymphoma, arguing that the effect of immunosuppression on the pathogenesis of lymphoma can not be excluded. Three areas worthy of study regarding the probable mechanisms for the occurrence of SLE and B-cell malignancies are discussed. A tumor suppressor gene PTEN may link the two disorders via a defective apoptosis pathway to eliminate hyperactive B and T cells in SLE. The accumulation of clonally expanded hyperactive B-cells that recognize self-antigens in the lymph nodes of SLE may predispose these B-cells to DNA breaks, facilitating tumorigenesis. Lastly, EBV infection, found to have a high prevalence in SLE patients, may serve as a common etiological factor in both disorders.

Autoimmune Disorders and Lymphomas

“…In addition to extrinsic risk factors, there are also defects in the immune system contributing to the development of both SLE and lymphomas, as the abnormal B-cell activation due to the chronic and persistent antigen-stimulation, cell-cycle deregulation and impaired apoptosis, which leads to uncontrolled cell proliferation, an exaggerated humoral autoimmune response and the increased risk of oncogene translocation (Illes et al, 2009). The impaired immune response in SLE is thus characterized by the accumulation of activated self-reactive B and T cells (Xu & Wiernik, 2001). Many studies have underlined the role of impaired apoptosis in this process.…”

“…Diffuse large B cell lymphoma is the most common subtype (King & Costenbader, 2007). After diagnosis of NHL a 5-year survival probability of 47%-50% has been estimated (Bernatsky et al, 2005b, Lofstrom et al, 2007, and mortality in patients with both diseases is usually due to progressive B-cell malignancy (Xu & Wiernik, 2001). …”

“…Mice with mutations of PTEN, a tumor suppressor gene, which impairs the Fas-mediated elimination of activated lymphocytes, develop SLE characterized by ANA antibodies, glomerulonephritis and lymphadenopathies (Di Cristofano et al, 1999). Also bcl-2, a proto-oncogene involved in the majority of B NHL, is highly expressed in SLE (Aringer et al, 1994), causing prolonged survival of auto-reactive B cells and thus favouring malignant transformation (Xu & Wiernik, 2001). The persistent clonal expansion of benign hyperactive B and T cells retained in lymph node of SLE patients in response to self-antigens exposes these cells to DNA damage, ultimately leading to neoplastic transformation (Xu & Wiernik, 2001).…”

“…Also bcl-2, a proto-oncogene involved in the majority of B NHL, is highly expressed in SLE (Aringer et al, 1994), causing prolonged survival of auto-reactive B cells and thus favouring malignant transformation (Xu & Wiernik, 2001). The persistent clonal expansion of benign hyperactive B and T cells retained in lymph node of SLE patients in response to self-antigens exposes these cells to DNA damage, ultimately leading to neoplastic transformation (Xu & Wiernik, 2001). Increased serum levels of type-I Interferons (IFNs a/b) is also associated with active SLE disease (Theofilopoulos et al, 2005).…”

Lymphoproliferative Disorders in Patients with Systemic Lupus Erythematosus

“…Rearrangements of V/D/J genes, receptor editing, somatic hypermutation, and class switching are responsible for DNA strand breaks that lead chromosomal aberrations that are in part responsible for lymphomagenesis (Küppers et al,1999). A reasonable hypothesis is that the accumulation of clonally expanded self-reactive B cells that recognize self-antigens in the lymph nodes may predispose these B cells to DNA breaks, facilitating tumorigenesis (Xu et al, 2001). In support of this viewpoint, lymph nodes of patients with SLE have extensive necrosis with apoptotic debris (self antigens), with numerous plasma cells within germinal centers.…”