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; accuracy; citrullination; developing devices; diagnostic tools.