To the Editor:

Current views on B-cell lymphomagenesis suggest that several exogenous factors, acting in a multi-step fashion upon a predisposing condition, may be involved in B-cell clonal expansion, a potentially prelymphomatous stage.1-3 By contrast, clinical/epidemiological and preliminary experimental studies have apparently shown that only H pylori infection is specifically involved in the pathogenesis of gastric B-cell clonality and MALT lymphoma.4 However, our previous data obtained in dyspeptics and patients with Sjögren's syndrome show that in a relevant proportion of cases B-cell clonality is not associated with H pylori infection.5,6 We have proposed that in Sjögren's syndrome H pylori in the stomach could merely act as one of several local triggers of lymphoproliferation.5,6 

In this study we tested whether hepatitis C virus (HCV) infection may be involved in the pathogenesis of gastric lymphoproliferation in Sjögren's syndrome. Sjögren's syndrome is a well-known example (such as AIDS) of predisposition to develop B-cell clonal expansion and lymphomas.7 On the other hand, HCV has been implicated in the genesis of non-Hodgkin's lymphoma8,9 and is often present in patients with Sjögren's syndrome and may actually be involved in its pathogenesis.10 

We determined B-cell clonality by VDJ-PCR in 27 patients with this disease previously screened for HCV (8 positive, by both anti-HCV and HCV-RNA, and 19 negative). All HCV-positive patients had normal hepatic function. We also studied H pylori infection in gastric biopsy specimens. Of all patients, 15 of 27 (56%) had gastric VDJ clonality. Of all VDJ-positive patients, 7 of 15 (47%) were also HCV-positive as opposed to 1 of 12 (8%) of VDJ-negative patients (Fisher's exact test: P < .05). Of all the HCV-positive patients 7 of 8 (87.5%) were also VDJ-positive. By contrast, H pylori infection was equally distributed among VDJ-positive and VDJ-negative patients (9 of 15 or 60% v 8 of 12 or 67%, respectively, not significant). HCV infection was associated with H pylori in 6 of 8 cases. Cryoglobulinemia was present in one patient per group.

These data show that HCV infection in patients with Sjögren's syndrome is strongly associated with gastric B-cell clonal expansion. In line with the reported possible involvement of HCV in the genesis of gastric11 and other B-cell lymphomas8 our findings indicate that this virus may represent an important (co)factor in early stages of gastric lymphoproliferation in Sjögren's syndrome.

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