Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyte-associated antigen 4, and programmed cell death 1 in primary Sjögren's syndrome.
OBJECTIVE
To assess salivary gland tissues obtained from patients with primary Sjögren's syndrome (SS) for the gene expression profile of the candidate genes TNFRSF6 (Fas), TNFSF6 (FasL), SSA1 (Ro52 alpha and the splice variant Ro52 beta), SSB (La), CTLA4, PDCD1 (PD-1), and ORM2, which were selected on the basis of their putative participation in salivary gland inflammation.


METHODS
Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the expression of messenger RNA (mRNA). Tissue localization of the expressed proteins was detected by immunohistochemistry.


RESULTS
Expression of mRNA was increased for Fas (5.1-fold; P < 0.001), FasL (8.8-fold; P < 0.05), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) (11.2-fold; P < 0.01), programmed cell death 1 (PD-1) (15.2-fold; P < 0.05), Ro52 alpha (3.0-fold; P < 0.01), La (2.3-fold; P < 0.05), and orosomucoid 2 (ORM2) (4.4-fold; P < 0.05) in patients compared with controls when GAPDH was used as endogenous standard in duplex runs. In single runs using 2 other endogenous standards (18S and beta-actin), statistically significant differences between patients and controls were confirmed for expression of Fas, FasL, CTLA-4, and PD-1, but this difference was not observed for Ro52 alpha, La, and ORM2. Expression of Ro52 beta mRNA was similar in patients and controls.


CONCLUSIONS
The present study demonstrates a substantial increase in expression of the negative regulator molecules PD-1 and CTLA-4 and the apoptotic signal molecules Fas and FasL in patients with primary SS compared with controls, which corresponded to the immunomorphologic pattern. The results strongly indicate that these molecules have central roles in the inflammatory process in the salivary glands of patients with primary SS.
Bolstad
Anne Isine
AI
Center for Medical Genetics and Molecular Medicine, University of Bergen, and Haukeland University Hospital, Bergen, Norway. anne.boldstad@gades.uib.no
Eiken
Hans Geir
HG
Rosenlund
Benedikte
B
Alarcón-Riquelme
Marta E
ME
Jonsson
Roland
R
D000069594:Abatacept; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics*; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression; D006801:Humans; D018796:Immunoconjugates; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012469:Salivary Glands / Q000737:chemistry / Q000503:physiopathology*; D012859:Sjogren's Syndrome / Q000503:physiopathology*; D019014:fas Receptor / Q000032:analysis / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D019014:fas Receptor; D000069594:Abatacept