Local cytokine expression in the progression toward B cell malignancy in Sjögren's syndrome.
OBJECTIVE
Sjögren'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)-1 beta, IL-2, IL-3, IL-4, IL-6, IL-6R, IL-9, IL-10, IL-12, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) 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-gamma, TNF-alpha, and TGF-beta 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-gamma expression in 3/7 cases and in 2/7 cases, respectively.


CONCLUSIONS
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.
De Vita
S
S
Department of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano PN, Italy.
Dolcetti
R
R
Ferraccioli
G
G
Pivetta
B
B
De Re
V
V
Gloghini
A
A
D'Agosto
A
A
Bartoli
E
E
Carbone
A
A
Boiocchi
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016207:Cytokines / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007372:Interferons / Q000032:analysis; D007378:Interleukins / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000737:chemistry* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000473:pathology
D016207:Cytokines; D007378:Interleukins; D007372:Interferons