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Stereotypic Rheumatoid Factors That Are Frequently Expressed in Mucosa‐Associated Lymphoid Tissue–Type Lymphomas Are Rare in the Labial Salivary Glands of Patients With Sjögren's Syndrome
Objective
Among autoimmune diseases, Sjögren's syndrome (SS) is most strongly associated with the development of malignant B cell lymphoma, in particular mucosa‐associated lymphoid tissue (MALT)–type lymphoma. Previously, we have shown that in ∼40% of cases of salivary gland MALT lymphoma, high‐affinity stereotypic rheumatoid factor (RF) B cell receptors, specific for IgG‐Fc, are expressed. This study was undertaken to investigate whether in the inflamed salivary glands of patients with SS, a similar RF‐biased Ig repertoire is present.
Methods
Extensive analyses of the B cell Ig VH region repertoire were performed on microdissected tissue samples from the labial salivary glands of 4 patients with SS.
Results
All SS labial salivary glands harbored expanded B cell clones, of which 1 or 2 were highly expanded and detected in >50% of the microdissected samples. However, among the identified 464 distinct Ig clonotypes, only 3 stereotypic RF–expressing clones were detected. In 2 patients with SS, an RF‐expressing clone was detected at low frequency in 1 of the microdissected samples, whereas 1 patient with SS harbored a highly expanded RF‐expressing clone that was detected in all microdissected samples and also detected in the peripheral blood. Two years after analysis of this sample, the latter patient developed a diffuse large B cell lymphoma originating from the same RF clone.
Conclusion
Inflamed labial salivary glands in patients with SS generally harbor 1 or 2 highly expanded B cell clones. The repertoire strongly biased toward stereotypic RFs in salivary gland MALT lymphomas is not a reflection of a similar repertoire in the inflamed salivary glands of patients with SS; rather, in the latter, the repertoire is based on a strong selection advantage of incidental stereotypic RF–expressing B cells.