Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting in weakness of voluntary muscles. It is caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction (NMJ). A characteristic pathology of patients with early onset MG is thymic hyperplasia with ectopic germinal centers (GC). However, mechanisms that trigger and maintain thymic hyperplasia are poorly characterized.
In order to determine the central mechanisms involved in the pathology, thymus samples from MG patients were assessed by histology and grouped based on appearance of GC compared to samples without them. We assessed the differential mRNA expression profiles between the two groups by GeneChip® Human Transcriptome Array 2.0. Partek Genomic Suite 6.6 and Transcript Analysis Console 2.0 programs were used for further analysis. Forty eight annotated mRNA transcripts were identified that were differentially expressed between the two groups with greater than 1.5 fold difference in expression (ANOVA p\u3c0.05). We verified their expression by RT-PCR. We identified Regulator of G protein Signaling 13 or RGS13 that is known to be expressed in GC B-cells and regulate responsiveness to chemokine signaling. Upregulation of RGS13 was found to be associated with specimens having GC. We verified its expression in GC by immunohistochemistry.
Gene ontology (GO) enrichment analysis and Ingenuity Pathway Analysis (IPA) core analysis of differentially expressed genes indicate involvement of immune response regulation and cell proliferation pathways, indicating their importance in GC formation and regulation
