Immunoglobulin gene rearrangements in lymphoplasmacytic infiltrates of labial salivary glands in Sjögren's syndrome. A possible predictor of lymphoma development.
OBJECTIVE
Sjögren's syndrome is an autoimmune disorder in which patients have a well-recognized risk of developing malignant lymphoma. Although some clinical parameters may herald the onset of lymphoma, few reliable histologic or molecular markers are available that predict progression to a malignant lymphoproliferative disorder. The purpose of this study was to identify the prevalence of immunoglobulin heavy chain monoclonality in labial gland biopsies of patients with Sjögren's syndrome and to compare this to clinical outcome.


METHODS
The polymerase chain reaction was applied to 76 sequential labial salivary gland biopsies from patients under investigation for Sjögren's syndrome. A seminested polymerase chain reaction technique was used on DNA extracted from formalin-fixed, paraffin-embedded tissue to amplify the V-D-J region of the immunoglobulin heavy chain gene. Thirty-four randomly selected labial salivary glands that showed nonspecific sialadenitis from patients without Sjögren's syndrome were used as controls.


RESULTS
Monoclonality, as defined by a single band on polyacrylamide gel electrophoresis was detected in 11 cases (14.5%). Of cases that showed monoclonality, four patients were subsequently diagnosed with extrasalivary lymphoma. In each case the rearranged bands in the lip biopsy and the lymphoma were the same size. In one patient who later developed lymphoma, a monoclonal rearranged immunoglobulin band was not identified. In addition, no cases of the translocation t(14;18) were identified by polymerase chain reaction in any of the lip biopsies showing heavy chain monoclonality or in any of the extrasalivary gland lymphomas.


CONCLUSIONS
These results suggest that monoclonal immunoglobulin heavy chain gene rearrangements are a relatively common finding in patients with Sjögren's syndrome and may prove to be a useful marker for predicting the progression to, and early detection of malignant lymphoma.
Jordan
R
R
Joint Department of Oral Pathology, Eastman Dental Institute, London, UK.
Diss
T C
TC
Lench
N J
NJ
Isaacson
P G
PG
Speight
P M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic; D016009:Chi-Square Distribution; D017931:DNA Primers; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008046:Lip; D018442:Lymphoma, B-Cell, Marginal Zone / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012470:Salivary Glands, Minor / Q000276:immunology / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000150:complications / Q000276:immunology*
D014408:Biomarkers, Tumor; D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains