IADR Abstract Archives

Gene expression profiling in Sjogren's patients: correlation with clinical features

Objective: Sjogren's syndrome (SS) is a complex autoimmune disease defined primarily by dry eyes and dry mouth (sicca symptoms). We have used Affymetrix U133A-GeneChip microarrays to compare peripheral blood gene expression profiles of SS (n=37) and Sicca (n=11) patients to normal subjects (n=22).

Methods: All SS patients fulfilled the 2002 American-European criteria for primary SS and 89% were seropositive for anti-Ro/SSA and/or anti-La/SSB autoantibodies. Sicca patients were clinically diagnosed with SS based on subjective symptoms of both dry eyes and dry mouth, and had at least one objective finding (Schirmer's test or unstimulated whole salivary flow), but were seronegative for anti-Ro/SSA and/or anti-La/SSB and failed to meet the criteria due to unavailable labial gland histopathology. Differentially expressed genes were defined using t-tests with nominal significance of p<0.001 and average fold change of >1.5. Hierarchical clustering was used to visualize patterns of differentially expressed genes across all patients vs. controls. Correlation coefficients were calculated for gene expression levels and quantified measures of autoantibodies, tear and salivary flow.

Results: A Total of 277 transcripts were differentially expressed between patients and controls. The majority of SS patients clustered together and overexpressed a group of Interferon (IFN) inducible genes that was not observed in sicca patients. The IFN signature was positively correlated to anti-Ro/SSA and anti-La/SSB titers and plasma cell counts, but negatively correlated to saliva and tear flow measurements (p<0.05).

Conclusions: These results indicate that subsets of patients with sicca manifestations can be identified using microarrays and overexpression of type I IFN pathway genes is prominent in SS patients. These results suggest multiple pathways may be involved in the pathophysiology of patients with sicca symptoms.

NIH:5Ro1-AR05782


AADR/CADR Annual Meeting
2006 AADR/CADR Annual Meeting (Orlando, Florida)
Orlando, Florida
2006
49
Oral Medicine & Pathology
  • Emamian, Eshrat S.  ( University of Minnesota, Minneapolis, MN, USA )
  • Rhodus, Nelson L.  ( University of Minnesota, Minneapolis, MN, USA )
  • Moser, Kathy L.  ( University of Minnesota, Minneapolis, MN, USA )
  • Tobon, Liliana M.  ( University of Minnesota, Minneapolis, MN, USA )
  • Leon, Joanlise  ( University of Minnesota, Minneapolis, MN, USA )
  • Leiran, Amber N.  ( University of Minnesota, Minneapolis, MN, USA )
  • Meyer, Carolyn M.  ( University of Minnesota, Minneapolis, MN, USA )
  • Baechler, Emily C.  ( University of Minnesota, Minneapolis, MN, USA )
  • Behrens, Timothy W.  ( University of Minnesota, Minneapolis, MN, USA )
  • Huang, Andrew J.w.  ( University of Minnesota, Minneapolis, MN, USA )
  • Segal, Barbara  ( University of Minnesota, Minneapolis, MN, USA )
    • Oral Session
    Oral Diseases: Potential New Diagnostic and Treatment Tools
    03/08/2006