Plant-Derived Chimeric Virus Particles for the Diagnosis of Primary Sjögren Syndrome.

Elisa Tinazzi,Caterina Bason,Claudio Lunardi,Antonio Puccetti,Linda Avesani,Roberta Zampieri,Elena Bartoloni,Mario Pezzotti,Chiara Lico,Matilde Merlin,Ruggero Beri

doi:10.3389/fpls.2015.01080

Abstract

Plants are ideal for the production of protein-based nanomaterials because they synthesize and assemble complex multimeric proteins that cannot be expressed efficiently using other platforms. Plant viruses can be thought of as self-replicating proteinaceous nanomaterials generally stable and easily produced in high titers. We used Potato virus X (PVX), chimeric virus particles, and Cowpea mosaic virus, empty virus-like particles to display a linear peptide (lipo) derived from human lipocalin, which is immunodominant in Sjögren’s syndrome (SjS) and is thus recognized by autoantibodies in SjS patient serum. These virus-derived nanoparticles were thus used to develop a diagnostic assay for SjS based on a direct enzyme linked immunosorbent assay format. We found that PVX-lipo formulations were more sensitive than the chemically synthesized immunodominant peptide and equally specific when used to distinguish between healthy individuals and SjS patients. Our novel assay therefore allows the diagnosis of SjS using a simple, low-invasive serum test, contrasting with the invasive labial biopsy required for current tests. Our results demonstrate that nanomaterials based on plant viruses can be used as diagnostic reagents for SjS, and could also be developed for the diagnosis of other diseases.

Highlights

Sjögren’s syndrome (SjS) is a complex chronic systemic autoimmune disease that may present alone as primary SjS or associated with other autoimmune diseases as secondary SjS
We enrolled 91 patients affected by primary SjS (pSjS), with a majority of female enrollees (86 female, 5 male) reflecting the sex-based prevalence of the disease
A control group of 120 subjects was enrolled, comprising 60 age/sex-matched healthy donors and 60 patients affected by other autoimmune disorders, i.e., 20 each with systemic sclerosis (SSc), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE)

Summary

Introduction

Sjögren’s syndrome (SjS) is a complex chronic systemic autoimmune disease that may present alone as primary SjS (pSjS) or associated with other autoimmune diseases as secondary SjS (sSjS). The anti-SSA (Ro) and anti-SSB (La) autoantibodies listed among the AECG criteria are common in other autoimmune diseases and do not offer a rigorous pSjS diagnosis at an early stage when other symptoms are absent (Shen et al, 2012). A labial biopsy is mandatory for confirmation, and is the only indicative diagnosis in the absence of autoantibodies and other symptoms (Patel and Shahane, 2014). This has driven researchers to seek more reliable autoantigens and autoantibodies suitable for early diagnosis

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Conclusion