Expression of proteasomal immunosubunit beta1i is dysregulated in inflammatory infiltrates of minor salivary glands in Sjogren's syndrome.
OBJECTIVE
Minor salivary gland specimens were analyzed to investigate dysregulation of the proteasome system in patients with Sjögren's syndrome (SS) and patients with sicca syndrome.


METHODS
Labial biopsy specimens from 17 patients with SS and 11 patients with non-autoimmunesicca syndrome were analyzed by immunohistochemistry for expression of the inducible proteasomal subunits ss1i, ss2i, and ss5i. The infiltrating subsets of lymphocytes were characterized using immunofluorescence stainings against the cell-surface markers CD20 and CD27. Two-dimensional electrophoresis and immunoblotting were used for detection of the proteasomal subunits ss1 and ss1i in peripheral blood monocyte cells. Gene expression of the constitutive subunits ss1, ss2, and ss5 and the corresponding inducible subunits ss1i, ss2i, and ss5i was further investigated at the mRNA level in small lip biopsies using real-time polymerase chain reaction.


RESULTS
The expression of ss1i in infiltrating and peripheral immune cells was altered in patients with SS compared to patients with non-autoimmune sicca syndrome and healthy controls. No significant differences were found in ss2i and ss5i expression between the same groups in small lip biopsies. Chisholm-Mason grade and ss1i expression were found to be inversely correlated (Spearman r = -0.461, p = 0.014). The phenotype and distribution of the lymphocytic infiltrate showed no differences between patients with primary and secondary SS regardless of ss1i expression.


CONCLUSIONS
The proteasomal ss1i subunit is dysregulated in peripheral white blood cells and in inflammatory infiltrates of minor salivary glands in patients with SS.
Morawietz
Lars
L
Department of Rheumatology and Clinical Immunology, Institute of Pathology, and Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Berlin, Germany.
Martinez-Gamboa
Lorena
L
Scheffler
Sonja
S
Hausdorf
Gert
G
Dankof
Anja
A
Kuckelkorn
Ulrike
U
Doerner
Thomas
T
Egerer
Karl
K
Burmester
Gerd-R
GR
Faustman
Denise L
DL
Feist
Eugen
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008046:Lip / Q000166:cytology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology*; D012470:Salivary Glands, Minor / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
D021122:Protein Subunits; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases