Genome-wide gene expression analysis of peripheral leukocytes in relation to the male predominance of Guillain-Barre syndrome: differential gene expression between male and female patients

Background: Guillain-Barre syndrome (GBS) fulfils most of the clinical features of an autoimmune disease except for its male predominance. No previous studies have evaluated the differential genome-wide expression between male and female GBS patients.

Objective: This study sought to identify differences between male and female GBS patients in the gene expression profiles of peripheral leukocytes.

Methods: We downloaded gene chip data-sets pertaining to peripheral leukocyte samples from GBS patients using the gene expression omnibus (submitted by Chang et al.) and applied hierarchical cluster analysis to detect whether there was a gender difference in genome-wide gene expression levels. Then, we identified the sexually differentially expressed genes using a bioinformatic approach and applied enrichment analysis to the gene ontology and Kyoto Encyclopaedia of Genes and Genomes terms to identify significant pathways related to these genes.

Results: We observed gender stratification among GBS patients. Twenty genes were expressed more highly in male patients and were enriched for functions, such as macrophage differentiation, leukocyte migration, bladder cancer, pathogenic Escherichia coli infection. In female patients, 62 genes were more highly expressed and were enriched for responses to viral infection and defence, retinoic acid-inducible gene I (RIG-I)-like receptors, cytoplasmic DNA sensing. Matrix metalloproteinase 9 (MMP9) seem to play an important role in the male predominance of GBS.

Conclusions: This study demonstrated gender differences in the genome-wide gene expression of patients with GBS. Bioinformatic approaches offer new means for identifying candidate genes and pathways relevant to the pathophysiology of GBS.