Abstract 1079: Expression of Proteasomal Immunosubunit Beta1i (LMP2) is Suppressed in Inflammatory Infiltrates of Minor Salivary Glands in Sjögren´s Syndrome

Thomas Grader-Beck

Authors

Sonja Scheffler, Lars Morawietz, Anja Dankof, Lorena Martinez Gamboa, Thomas Doerner, Gerd-Rüdiger Burmester, Eugen Feist. Charité University Hospital, Berlin, Germany

Purpose

Based on recent reports stating an unusual composition of immunoproteasoms in peripheral blood mononuclear cells of patients with Sjögren´s syndrome as well as similar findings in spleen cells of the NOD mouse model for diabetes and Sjögren, we studied the protein expression of proteasomal immunosubunits in infiltrating immune cells in minor salivary glands of patients with sicca syndrome.

Methods

Labial biopsy specimen from 28 patients with suspected Sjögren´s syndrome were analyzed by immunohistochemistry for the expression of proteasomal immunosubunits beta1i (LMP2), beta2i (MECL1) and beta5i (LMP7). Additionally, the Chisholm-Mason grade was determined for each biopsy describing the extent of lymphocyte infiltration and focus-like aggregation. Patients were diagnosed according to the US-European consensus classification (2002), diagnoses were primary Sjögren´s syndrome (pSS, 14 patients), secondary Sjögren´s syndrome (sSS, 3 patients) and sicca syndrome without autoimmune background (11 patients).

Results

The expression of beta1i (LMP2) in infiltrating immune cells was significantly lower in the Sjögren group (pSS and sSS) compared to patients with non-autoimmune sicca syndrome (p=0.019). No significant differences were found in beta2i (MECL1) and beta5i (LMP7) expression comparing the same groups. Chisholm-Mason grade and beta1i (LMP2) expression were inversely correlated (Spearman r= -0.461, p=0.014). Interestingly, in patients with Sjögren´s syndrome under immunsuppressive therapy beta1i (LMP2) was expressed on a higher level, comparable to patients with sicca syndrome.

Conclusions

We could demonstrate that a suppression of beta1i (LMP2) occurs not only in peripheral white blood cells in Sjögren´s syndrome, but also in glandular infiltrates which play an important role in the inflammatory autoimmune process. This downregulation appears to be specific for Sjögren´s syndrome as it was not seen in patients with sicca syndrome without autoimmune disease. Data from ongoing mouse studies are supporting these findings. Given the known influence of proteasomal subunit composition on quality and quantitiy of the produced antigenic MHC I epitopes, the results suggest a possible pathogenetic role of the deregulation of immunosubunit beta1i (LMP2) in Sjögren´s syndrome.