An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders

被引:85
作者
Alghamdi, Mohammed [1 ,2 ]
Alasmari, Doaa [1 ]
Assiri, Amjad [1 ]
Mattar, Ehab [1 ]
Aljaddawi, Abdullah A. [1 ]
Alattas, Sana G. [1 ]
Redwan, Elrashdy M. [1 ,3 ]
机构
[1] King Abdulaziz Univ, Dept Biol Sci, Fac Sci, POB 80203, Jeddah 21589, Saudi Arabia
[2] King Abdulaziz Univ, Lab Dept, Univ Med Serv Ctr, POB 80200, Jeddah 21589, Saudi Arabia
[3] City Sci Res & Technol Applicat, Therapeut & Protect Prot Lab, Prot Res Dept, Genet Engn & Biotechnol Res Inst, Alexandria 21934, Egypt
关键词
SYSTEMIC-LUPUS-ERYTHEMATOSUS; MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS LESIONS; REGULATORY T-CELLS; NEUTROPHIL EXTRACELLULAR TRAPS; PEPTIDYLARGININE DEIMINASE 2; EARLY RHEUMATOID-ARTHRITIS; CENTRAL-NERVOUS-SYSTEM; FIBRILLARY ACIDIC PROTEIN; ANTI-CCP ANTIBODIES;
D O I
10.1155/2019/7592851
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:39
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