Local cytokine expression in the progression toward B cell malignancy in Sjogren's syndrome

Objective. Sjogren's syndrome (SS) has been indicated as an ideal human model to investigate B cell lymphomagenesis. Our aim was to investigate similarities or differences in cytokine expression in both prelymphomatous and frank B cell lymphomatous SS lesions, as well as in SS related lesions versus SS unrelated malignant B cell non-Hodgkin's lymphomas. Methods. The mRNA expression of interleukin (IL)-1β, IL-2, IL-3, IL-4, IL-6, IL-6R, IL- 9, IL-10, IL-12, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN- γ), and transforming growth factor beta (TGF-β) was analyzed by a sensitive reverse transcriptase polymerase chain reaction technique in 10 SS tissue samples from 10 consecutive patients [7 nonmalignant parotid myoepithelial sialadenitis (MESA) lesions with evidence of B cell clonal expansion, and 3 B cell non-Hodgkin's lymphomas] as well as a series of 11 SS unrelated B cell non-Hodgkin's lymphomas. Results. IL-1, IL-2, IL-3, IL-6, IL-6R, IL-10, IL- 12, IFN-γ, TNF-α, and TGF-β mRNA was expressed in all or in the vast majority of the samples analyzed. IL-4 mRNA was detected in 2/3 SS related and in 3/11 SS unrelated non-Hodgkin's lymphomas, while SS related MESA samples were characterized by an IL-4 negative pattern and lacked IL-3 or IFN-γ expression in 3/7 cases and in 2/7 cases, respectively. Conclusion. Many cytokines may be involved in the evolution of prelymphomatous to definite B cell malignant lesions in SS, as well as in the development of SS unrelated B cell non-Hodgkin's lymphomas. A putative pathobiological role of the IL-12/IL-4 balance, in the presence of cytokines that may sustain B cell proliferation (i.e., IL-3, IL-6, IL-10), may represent a major point for future research. Finally, our data reinforce the view of SS as a human model of B cell lymphomagenesis.