Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders

Abstract

. Jønsson V, Wiik A, Hou‐Jensen K, Christiansen M, Ryder LP, Madsen HO, Geisler C, Hansen MM, Thomsen K, Vorstrup S, Svejgaard A (Rigshospital, University of Copenhagen and State Serum Institute, Copenhagen, Denmark). Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders. J Intern Med 1999; 245: 277–86. Objective. To examine the relationship between autoimmunity and extranodal lymphocytic infiltrates in different lymphoproliferative disorders with immunoglobulin alterations. Subjects and design. A clinical review combined with a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of undetermined significance, three with common variable immunodeficiency, 147 with chronic lymphocytic leukaemia, 57 with Waldenström's macroglobulinaemia and 145 with non‐Hodgkin's malignant lymphoma. Setting. A university hospital and The State Serum Institute in Copenhagen. Intervention. Clinical examination of each patient with special attention to chronic inflammatory and autoimmune manifestations. Biopsies were taken from non‐infectious infiltrates, some of which were additionally tested with PCR analysis for gene rearrangements. Serological screening with a test battery for various autoantibodies was used in combination with techniques for the detection of M‐components and monoclonal B‐cell proliferation. Main outcome measures. Clinical and/or serological autoimmune manifestations, M‐component and other immunoglobulin alterations, and inflammatory tissue changes were studied in patients with chronic inflammatory, polyclonal or oligoclonal pseudolymphomas and in monoclonal, malignant extranodal lymphomas. Results. In 380 consecutive patients, 49 (12.9%) had extranodal manifestations, of whom 47 also had autoimmune manifestations. Nearly half of the 47 patients had more than one autoimmune manifestation. There was a strong correlation between clinical signs and corresponding autoantibodies such as anti‐SSA and ‐SSB antibodies in Sjögren's syndrome (10 cases), antithyroid peroxidase antibodies in thyroiditis and Graves' disease (10 cases), and parietal cell antibodies in gastric ulcers with maltoma (12 cases). Clinical and serological signs of autoimmunity correlated strongly with female sex (34, 72% women; and 13, 28% men) and with immunoglobulin alterations. Conclusions. To our knowledge this is the first systematic review of B‐lymphoproliferative and autoimmune disorders indicating that pseudolymphoma and malignant lymphomas, including maltomas, may develop in the context of a permanent autoantigenic drive.

Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

“…4,35,36 In the context of these prolonged lymphoid reactive proliferations, the growth of a pathologic clone can progressively replace the normal lymphoid population, giving rise to a MALT lymphoma. 5,6,37,38 The peculiar pathogenetic features of primary gastric MALT lymphomas, with their implications on the clinical behavior of this entity, 4 and data suggesting a distinct pattern of disease relapse and survival of the primary intestinal localizations 39 led us to collect a series of primary nongastric MALT lymphomas including primary lymphomas of the small and large bowel.…”

The epidemiology of non-Hodgkin's lymphoma

“…Although immunosuppressive drugs used in the treatment of these conditions may cause an increase in NHL incidence, evidence suggests that the persistent inflammatory activity of the autoimmune process may have a direct link with increased risk of lymphomagenesis (Jonsson et al, 1999). Wahl et al (1983) demonstrated that these conditions may be accompanied by impaired T-cell function, which may interfere with an immune response to viruses and emerging malignant cells.…”

Helicobacter pylori infection and gastric cancer

“…91 Evidence for antigen-driven clonal expansion initially arose from in vitro experiments showing that B-cells from low-grade gastric MALT lymphomas are stimulated to proliferate when cultured with heat-killed H. pylori. 92 This antigenic stimulation is observed only with certain H. pylori strains, and is dependent on tumour-derived T-cell activation by H. pylori.…”