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.

1
Ludwig
CU
Gencik
M
Shipman
R
Multistep transformation in low-grade lymphoproliferative diseases.
Ann Oncol
4
1993
825
2
Dolcetti R, Boiocchi M: Cellular and molecular bases of B-cell clonal expansions. Clin Exp Rheum 14:S3, 1996
3
Aisenberg
AC
Coherent view of non-Hodgkin lymphoma.
J Clin Oncol
13
1995
2565
4
Isaacson
PG
Gastric lymphoma and Helicobacter pylori.
N Engl J Med
330
1994
1310
5
Sorrentino D, Ferraccioli GF, Labombarda A, DeVita S, Avellini C, Beltrami CA, Bartoli E: Helicobacter pylori, gastric MALT and B-cell clonality. Clin Exp Rheum 14:S51, 1996 (suppl)
6
DeVita
S
Ferraccioli
GF
Avellini
C
Sorrentino
D
Dolcetti
R
DiLoreto
C
Bartoli
E
Boiocchi
M
Beltrami
CA
Widespread clonal B-cell disorder in Sjögren's syndrome predisposing to Helicobacter pylori-related gastric lymphoma.
Gastroenterology
110
1996
1969
7
Sugai S, Shimizu S, Kunda S: Lymphoproliferative disorders in patients with Sjögren's syndrome. Scand J Rheumatol S61:118, 1986 (suppl)
8
Ferri
C
La Civita
L
Caracciolo
F
Bellesi
G
Zignego
AL
Hepatitis C virus and lymphoproliferative disorders.
Blood
87
1996
4730
9
Silvestri
F
Pipan
C
Barillari
G
Zaja
F
Fanin
R
Infanti
L
Russo
D
Falasca
E
Botta
GA
Baccarani
M
Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders.
Blood
87
1996
4296
10
Koike
K
Moriya
K
Ishibashi
K
Yotsuyanagi
H
Shintani
Y
Fujie
H
Kurokawa
Y
Matsuura
Y
Miyamura
T
Sialoadenitis histologically resembling Sjögren's syndrome in mice transgenic for hepatitis C virus envelope genes.
Proc Natl Acad Sci USA
94
1997
233
11
Luppi
M
Longo
G
Ferrari
MG
Ferrara
L
Marasca
R
Barozzi
P
Morselli
M
Emilia
G
Torelli
G
Additional neoplasms and HCV infection in low-grade lymphoma of MALT type.
Br J Haematol
94
1996
373
Sign in via your Institution