CLONAL SALIVARY-GLAND INFILTRATES ASSOCIATED WITH MYOEPITHELIAL SIALADENITIS (SJOGRENS-SYNDROME) BEGIN AS NONMALIGNANT ANTIGEN-SELECTED EXPANSIONS

Myoepithelial sialadenitis (MESA) is the reactive salivary gland lymph oid infiltrate that occurs in patients with Sjogren's syndrome. Althou gh it is well established that mucosa-associated lymphoid tissue (MALT )-type lymphomas may develop from MESA, the issue of whether monoclona l B-cell populations in early MESA-associated lesions represent MALT l ymphomas or more benign types of expansions has been very controversia l. in addition, it is unknown whether antigen stimulation plays a role in the development or growth of MESA-associated clones. To investigat e these issues, we have analyzed the Ig VH genes used by MESA-associat ed clones in sequential biopsies obtained from contralateral sites of seven different patients. In three cases, single clones were identifie d in the follow-up biopsies that were distinct from the single clones identified in the initial specimens, whereas in three other cases, the same clone was identified in both the initial and subsequent specimen s. In the remaining case, two clones were identified in the second bio psy specimen, one of which was distinct from the initial clone. Of the 11 distinct clones identified in the 14 specimens that were analyzed, 8 were derived from a V1-69 VH gene segment, whereas the other 3 were derived from a V3-7 VH gene segment. In addition, the MESA clones als o showed conserved amino acids sequence motifs in their third compleme ntarity-determining regions (CDR3), some of which were encoded by N nu cleotides. The marked VH gene restriction along with the similar CDR3 sequences suggests that MESA-associated clones even from different pat ients may bind the same or similar antigens and are selected for clona l expansion on that basis. The high rates of ongoing VH gene mutation observed in some of the cases futher suggest that the growth of early MESA clones is still dependent on antigen stimulation. In addition, ou r finding that different biopsies from the same patient may contain di stinct clones indicates that some MESA-associated clones have not yet evolved to malignant lymphomas. (C) 1998 by The American Society of He matology.