A protein undergoes many types of posttranslation modification. Citrullination is one of these modifications, where an arginine amino acid is converted to a citrulline amino acid. This process depends on catalytic enzymes such as peptidylarginine deiminase enzymes (PADs). This modification leads to a charge shift, which affects the protein structure, protein-protein interactions, and hydrogen bond formation, and it may cause protein denaturation. The irreversible citrullination reaction is not limited to a specific protein, cell, or tissue. It can target a wide range of proteins in the cell membrane, cytoplasm, nucleus, and mitochondria. Citrullination is a normal reaction during cell death. Apoptosis is normally accompanied with a clearance process via scavenger cells. A defect in the clearance system either in terms of efficiency or capacity may occur due to massive cell death, which may result in the accumulation and leakage of PAD enzymes and the citrullinated peptide from the necrotized cell which could be recognized by the immune system, where the immunological tolerance will be avoided and the autoimmune disorders will be subsequently triggered. The induction of autoimmune responses, autoantibody production, and cytokines involved in the major autoimmune diseases will be discussed.

Background: Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein autoantibodies (ACPAs) are useful tools for rheumatoid arthritis (RA). The presence of ACPAs against citrullinated proteins (CPs), especially citrullinated fibrinogen (cFBG), seems to be a useful serological marker for diagnosing RA. RA patients’ sera were found to be enriched in exosomes that can transmit many proteins. Exosomes have been found to express citrullinated protein such as cFBG. Objective: We conducted this study in two stages. In the first phase, we aimed to evaluate the association between autoantibodies and risk factors. In the next step, ACPA-positive serum samples from the first phase were subjected to exosomal studies to explore the presence of cFBG, which is a frequent target for ACPAs. Methods: We investigated the autoantibodies in one hundred and sixteen Saudi RA patients and correlated with host-related risk factors. Exosomes were extracted from patients’ sera and examined for the presence of cFBG using monoclonal antibodies. Results: The study reported a high female-to-male ratio of 8:1, and seropositive RA (SPRA) was more frequent among included RA patients. The frequency and the levels of ACPAs were similar in both genders. Autoantibodies incidences have a direct correlations with patient age, while the average titers decreased as the age increased. Further, the highest incidence and levels of autoantibodies were reported in patients with RA duration between 5 and 10 years. Smoking and family history have no impact on autoantibody, except for ACPAs titers among smokers’ RA. Our analysis of serum exosomes revealed that about 50% of SPRA patients expressed cFBG. Conclusions: The female-to-male ratio is 8:1, which is higher than the global ratio. We can conclude that patients’ age and disease duration contribute to the autoantibodies, particularly RF and anti-MCV, whereas smoking and family history had no effects on autoantibodies. We detected cFBG in all exosomes from SPRA patients; thus, we suggest that the precise mechanism of exosomes in RA pathogenesis can be investigated to develop effective treatment strategies.

Background: Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPAs) are useful tools for rheumatoid arthritis (RA). The presence of ACPAs against citrullinated proteins (CPs), especially citrullinated fibrinogen (cFBG), seems to be a useful serological marker for diagnosing RA. RA patients' sera were found to be enriched in exosomes that can transmit many proteins. Exosomes have been found to express citrullinated protein, such as cFBG. Methods: We investigated the autoantibodies in one hundred sixteen Saudi RA patients and correlated with host-related risk factors. Exosomes were extracted from patients' sera and examined for the presence of cFBG using monoclonal antibodies. Results: The study reported high female-to-male ratio of 8:1, and the seropositive RA (SPRA) was more frequent among included RA patients. The frequency and the levels of ACPAs were similar in both genders. Autoantibodies incidences have a direct proportion with patients, age, while the average titers decreased as the age increased. Further, the highest incidence and levels of autoantibodies were reported in patients with RA duration between 5-10 years. Smoking and family history have no impact on autoantibody, except for ACPAs titers among smokers RA. Our analysis of serum exosomes revealed that about 50% of SPRA patients expressed cFBG. Conclusion: Further studies are needed to confirm the increasing rate of RA among Saudi patients, as well as the spike in the number of women affected by the disease. The role of autoantibodies in RA can be improved by conducting in-depth research on ACPA in conjunction with other factors, such as genetic, cellular, and even lifestyle factors. Proteomic study of serum exosomes can be performed and validated in larger populations to develop new diagnostic and prognostic markers for RA. It can also be assessed to fill in the gaps in the current understanding of the etiology of RA to enhance disease management.