Autoantibodies to La/SSB in patients with primary Sjogren's syndrome (pSS)are associated with upregulation of La/SSB mRNA in minor salivary gland biopsies (MSGs)

Recent studies have shown that minor salivary glands (MSGs) of patients wit h primary Sjogren's syndrome (pSS) are sites of anti-La/SSB autoantibody pr oduction. The aim of this study was to investigate the expression of La/SSB mRNA in MSGs of patients with pSS. La/SSB mRNA expression was studied by i n situ hybridization in six biopsies of pSS patients with anti-La/SSB antib odies, nine pSS patients without anti-La/SSB and 10 patients with non-speci fic sialadenitis. Oligonucleotide probes corresponding to c-DNA encoding fo ur linear epitopes of La/SSB (bp 423-471, bp 861-909, bp 903-954 and bp 104 8-1092) were utilized, cDNA encoding linear epitopes of Ro52 (bp 786-837), Ro60 (bp 654-702) and the housekeeping genes of Sm and GAPDH were used as c ontrols. The results were expressed as percent of positive cells by image a nalysis. Serum levels of anti-La/SSB autoantibodies were correlated with th e presence and the intensity of La/SSB mRNA labeling. All pSS patients with anti-La/SSB antibodies in their serum expressed mRNA transcripts of epitop es 301-318 aa and 349-364 aa (encoded by the cDNA probes bp 903-954 and bp 1048-1092 respectively), predominantly in acinar and mononuclear cells of M SGs. These epitopes are the major targets of anti-La/SSB antibodies. Serum levels of anti-La/SSB antibodies were correlated with the number of positiv ely stained cells in MSGs. Two of the nine pSS patients without anti-La/SSB autoantibodies and 2/10 non-pSS patients expressed the mRNA of the La/SSB molecule. The probes of RO52 and Ro60 epitopes did not react, while mRNA en coding the housekeeping genes of Sm and GAPDH was positive in all samples. In conclusion, pSS patients with anti-La/SSB antibodies showed upregulation of La/SSB mRNA in acinar and mononuclear cells of MSGs. Thus, active synth esis of La/SSB in MSGs of pSS seems to play an important role in the autoim mune response of the affected tissues. (C) 1999 Academic Press.