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Review
. 2019 Nov 25:2019:7592851.
doi: 10.1155/2019/7592851. eCollection 2019.

An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders

Mohammed Alghamdi  1   2 , Doaa Alasmari  1 , Amjad Assiri  1 , Ehab Mattar  1 , Abdullah A Aljaddawi  1 , Sana G Alattas  1 , Elrashdy M Redwan  1   3
Affiliations
Review

An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders

Mohammed Alghamdi et al. J Immunol Res. .

Abstract

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.

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Conflict of interest statement

All authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
The chemical reaction of (a) citrullination and (b) carbamylation.
Figure 2
Figure 2
PAD gene cluster organization. Ideograms showing the location and orientation of the PAD gene clusters of human chromosome 1, mouse chromosome 4, and rat chromosome 5.
Figure 3
Figure 3
(a) Myelinated nerve fiber is shown with salutatory conduction of action potential. (b) Transverse section of myelinated axon at the internode. (c) Bilayer membranes and with integrated MBP and PLP. (d) Phosphatidylethanolamine (PE).
Figure 4
Figure 4
The role of MBP citrullination involved in MS pathogenesis.
Figure 5
Figure 5
Cross-section of the human brain: normal individual brain (left) and brain from an AD patient (right). Overall shrinkage of brain tissue seen in AD brain with observed expanded sulci and shrinkage of the gyri. In addition, the ventricles seen to be enlarged.
Figure 6
Figure 6
Schematic cross-section of BBB showing the cerebral capillary associated with vascular cells (pericytes and endothelial cells), glial cells (astrocytes), and neurons.
Figure 7
Figure 7
Normal brain (left) and AD brain (right) showing the extracellular (β-amyloid plaques) and intracellular (neurofibrillary tangles).
Figure 8
Figure 8
Neutrophil extracellular traps (NETs).
Figure 9
Figure 9
Immune dysregulation in SLE. Above: balanced immune tolerance between T-effector cells and Tregs. Below: insufficiency and deficiency of Tregs result in autoimmunity.
Figure 10
Figure 10
Schematic view of (a) normal joint and (b) RA joint.
See this image and copyright information in PMC

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