Advances in the diagnosis of autoimmune diseases based on citrullinated peptides/proteins

ABSTRACT

Introduction: Autoimmune diseases are still one of the hard obstacles associated with humanity. There are many exogenous and endogenous etiological factors behind autoimmune diseases, which may be combined or dispersed to stimulate the autoimmune responses. Protein citrullination represents one of these factors. Harnessing specific citrullinated proteins/peptides could early predict and/or diagnose some of the autoimmune diseases. Many generations of diagnostic tools based on citrullinated peptides with comparable specificity/sensitivity are available worldwide.

Areas covered: In this review, we discuss the deimination reaction behind the citrullination of most known autoantigens targeted, different generations of diagnostic tools based on citrullinated probes with specificity/sensitivity of each as well as newly developed assays. Furthermore, the most advanced molecular analytical tools to detect the citrullinated residues in the biological fluid and their performance are also evaluated, providing new avenues to early detect autoimmune diseases with high accuracy.

Expert opinion: With the current specificity/sensitivity tools available for autoimmune disease detection, emphasis must be placed on developing more advance and effective, early, rapid, and simple diagnostic devices for autoimmune disease monitoring (similar to a portable device for sugar test at home). The molecular analytical devices with dual and/or multiplexe functions should be more simplified and invested in clinical laboratories.

KEYWORDS:

• Autoimmune diseases
• citrullination
• diagnostic tools
• developing devices
• accuracy

Article highlights

• Citrullination and genetic predisposition are important risk factors for developing RA.

• PADs enzyme catalysis arginine residues to citrulline in a citrullination process which breach the immune tolerance to produce anti-citrullinated peptides/proteins antibodies (ACPAs), which represent an essential contributor to RA pathogenesis and joint inflammation.

• ACPAs are the hallmark in RA that represent diagnostic and predictive markers for it, and accordingly, many assay generations have been developed for detecting ACPAs.

• High throughput multiplex immunoassays have been developed for detecting and quantifying multiple markers in a single run using a small sample volume.

• Mass spectrometry is a useful and effective tool for detecting citrullinated peptide and identifying the citrullinated sites precisely.

• Extracellular vesicles have recently been considered as a biological marker for RA as they can carry and represent citrullinated peptides/proteins to the immune cells.

Declaration of interest

The author(s) have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.