B-cell lymphoproliferation in primary Sjögren's syndrome

Sjögren's syndrome (SS) is characterized by lymphocytic infiltration of the exocrine glands, along with a polyclonal B-cell activation which is illustrated by the presence of multiple autoantibodies against organ and non-organ specific autoantigens. Lymphoproliferative disorders present with a higher frequency in patients with Sjögren's syndrome. The spectrum of lymphoproliferation extends from an increased frequency of circulating monoclonal immunoglobulins, free light chains and mixed monoclonal cryoglobulins (type II cryoglobulinemia) to an increased frequency of non-Hodgkin's lymphoma. In fact, patients with Sjögren's syndrome have a 44-times higher risk of developing lymphoma compared to the normal population. Several studies have shown that the affected exocrine glands are the major site of monoclonal B-cell proliferation in SS. This has been demonstrated by both immunophenotyping (an increased proportion of kappa:lambda light chains in the B-cells infiltrating the salivary glands) and immunogenotyping studies (monoclonal or oligoclonal light chain gene rearrangements in the salivary glands). The monoclonal rheumatoid factors in the sera of patients with SS share common cross-reactive idiotypes. The presence of these cross-reactive idiotypes is correlated with a higher frequency of extraglandular manifestations, circulating monoclonal immunoglobulins and autoantibodies. The lymphomas, which appear, may vary in type and location; immunocytomas, and intermediate grade and high grade non-Hodgkin's lymphomas have been described. Predictive factors for the development of lymphoma in SS include clinical signs such as lymphadenopathy, splenomegaly, and parotid gland enlargement, as well as laboratory parameters such as the presence of mixed monoclonal cryoglobulinemia and the presence of immunoglobulins bearing the cross-reactive idiotypes 17109 (Vk IIIb-related) and G-6 (VH1-related).