title: Autoantibodies to La/SSB in patients with primary Sjögren's syndrome (pSS) are associated with upregulation of La/SSB mRNA in minor salivary gland biopsies (MSGs).
abstract: Recent studies have shown that minor salivary glands (MSGs) of patients with primary Sjögren's syndrome (pSS) are sites of anti-La/SSB autoantibody production. 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 in situ hybridization in six biopsies of pSS patients with anti-La/SSB antibodies, nine pSS patients without anti-La/SSB and 10 patients with non-specific sialadenitis. Oligonucleotide probes corresponding to c-DNA encoding four linear epitopes of La/SSB (bp 423-471, bp 861-909, bp 903-954 and bp 1048-1092) 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 controls. The results were expressed as percent of positive cells by image analysis. Serum levels of anti-La/SSB autoantibodies were correlated with the presence and the intensity of La/SSB mRNA labeling. All pSS patients with anti-La/SSB antibodies in their serum expressed mRNA transcripts of epitopes 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 MSGs. These epitopes are the major targets of anti-La/SSB antibodies. Serum levels of anti-La/SSB antibodies were correlated with the number of positively 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 encoding 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 synthesis of La/SSB in MSGs of pSS seems to play an important role in the autoimmune response of the affected tissues.
authors.affiliation: Department of Pathophysiology, Medical School, National University of Athens, Athens, Greece.
authors.forename: A G
authors.initials: AG
authors.lastname: Tzioufas
authors.forename: I
authors.initials: I
authors.lastname: Hantoumi
authors.forename: M
authors.initials: M
authors.lastname: Polihronis
authors.forename: G
authors.initials: G
authors.lastname: Xanthou
authors.forename: H M
authors.initials: HM
authors.lastname: Moutsopoulos
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology*; D001706:Biopsy; D005260:Female; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger; D012261:Ribonucleoproteins / Q000235:genetics* / Q000276:immunology*; D012470:Salivary Glands, Minor / Q000276:immunology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation; D000097585:SS-B Antigen
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D000097585:SS-B Antigen