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Genome-wide expression analysis suggests unique disease-promoting and disease-preventing signatures in Pemphigus vulgaris

Genes & Immunity volume 14, pages 487–499 (2013)Cite this article

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Abstract

To evaluate pathogenetic mechanisms underlying disease development and progression in the autoimmune skin disease Pemphigus vulgaris (PV), we examined global peripheral blood gene expression in patients and healthy controls. Our goals were to: (1) assign blood gene expression signatures to patients and controls; (2) identify differentially expressed genes (DEGs) and investigate functional pathways associated with these signatures; and (3) evaluate the distribution of DEGs across the genome to identify transcriptional ‘hot spots’. Unbiased hierarchical clustering clearly separated patients from human leukocyte antigen (HLA)-matched controls (MCRs; ‘disease’ signature), and active from remittent patients (‘activity’ signature). DEGs associated with these signatures are involved in immune response, cytoskeletal reorganization, mitogen-activated protein kinase (MAPK) signaling, oxidation-reduction and apoptosis. We further found that MCRs carrying the PV-associated HLA risk alleles cluster distinctly from unmatched controls (UMCR) revealing an HLA-associated ‘control’ signature. A subset of DEGs within the ‘control’ signature overlap with the ‘disease’ signature, but are inversely regulated in MCR when compared with either PV patients or UMCR, suggesting the existence of a ‘protection’ signature in healthy individuals carrying the PV HLA genetic risk elements. Finally, we identified 19 transcriptional ‘hot spots’ across the signatures, which may guide future studies aimed at pinpointing disease risk genes.

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Acknowledgements

We are grateful for resources provided by The Research Technology Support Facility and the Genomics Core at Michigan State University. We thank Venice Cercado for technical assistance in extracting RNA and performing the microarray studies. Finally, we thank the study participants without whom this study would not have been possible.

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  1. Department of Dermatology, University at Buffalo, Buffalo, NY, USA

    R Dey-Rao, K Seiffert-Sinha & A A Sinha

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Correspondence to A A Sinha.

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Dey-Rao, R., Seiffert-Sinha, K. & Sinha, A. Genome-wide expression analysis suggests unique disease-promoting and disease-preventing signatures in Pemphigus vulgaris. Genes Immun 14, 487–499 (2013). https://doi.org/10.1038/gene.2013.44

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