[Clonal B-cell reaction in Sjögren disease and Hashimoto autoimmune thyroiditis]

Autoimmune diseases are defined as specific, adapted immune reactions against self-antigens. These antigens were attacked by activated, autoaggressive T-Cells in most cases. However, since introduction of the MALT concept it became clear, that particularly in the autoimmune diseases of the MALT specific subpopulations of B-cells play an important role. In this study, the B-cells in the thyroid gland of 40 patients suffering from Hashimoto's disease and 25 patients with Sjögrens syndrome and enlargement of the salivary glands were immunophenotyped and molecular-genetically investigated. The molecular-genetical investigation included PCR based amplification of immunoglobulin heavy chain CDR III region and the T-cell receptor gamma chain (TCR-gamma). By immunophenotyping, in the salivary glands monocytoid B-cells could be identified as intraepithelial effector cells in nearly all cases, whereas in the thyroid gland mostly marginal zone cells in the follicle epithelium were observed. In 13 biopsy specimen from salivary gland, clonal rearrangements of TCR-gamma, and in 9 cases of patients with Sjögren's syndrome JH rearrangements could be detected. Monoclonal TCR-gamma rearrangements were identified in 9/40 patients suffering from autoimmunethyroiditis Hashimoto. In 8/40 thyroid gland biopsies a monoclonal JH-rearrangement could be found. Within 11/25 patients with Sjögren's syndrome and in 23/40 patients with M. Hashimoto polyclonal rearrangements were observed. Within all biopsy specimen of patients with monoclonal rearrangements, lymphoepithelial lesions or lymphoepithelial destructions could be identified immunohistochemically. Additionally, in 2 biopsies from salivary gland and in one specimen from thyroid gland the transition from autoimmune disease into a secondary high grade lymphoma was observed. In 26/40 patients with M. Hashimoto and in 11/25 patients with Sjögren's syndrome the transition in a subsequent low grade B cell lymphoma of MALT-type was found. These results lead to the following conclusions: 1. clonal rearrangements of tumor forming B-cells in both autoimmune diseases investigated can be interpreted as facultative malignant. 2. Intraepithelial B-cells probably are the promotors of the autoimmune process and--in case of clonal evolution and immortalisation--can be regard as causative agent in the development of primary extranodal B-cell lymphoma.