Anti-Citrulline Antibodies in the Diagnosis and Prognosis of Rheumatoid Arthritis: Evolving Concepts

Abstract

Citrulline is a non-standard amino acid that can be incorporated into proteins only by post-translational modification of arginine by peptidylarginine deiminase (PAD) enzymes during a variety of biologic processes, including inflammation. Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, with a prevalence of 0.3 to 1% worldwide, which leads to progressive joint erosion and substantial disability if not treated early. A reliable and specific test for a marker present early in the disease would be useful to identify RA patients prior to the occurrence of joint damage. A new group of autoantibodies, the anti-cyclic citrullinated peptide antibodies (anti-CCP), can be detected in up to 80% of patients with RA, are highly specific for the disease, and may be of value for both the diagnosis and the prognosis of RA. The fact that these antibodies may appear before the onset of the disease suggests a potential role in primary prevention. Interestingly, they may also play a role in the pathophysiology of this disabling disease. The process of citrullination, its physiologic role, and citrullination-related pathologies, as well as the use of anti-citrullinated protein antibody tests (ACPA) for the early diagnosis and prognosis of RA and their potential role in the pathophysiology of the disease, are discussed.

Key words :

• Anti-cyclic citrullinated peptide antibodies
• antiperinuclear factor
• autoantibodies
• citrulline
• diagnosis
• early arthritis
• rheumatoid arthritis
• primary prevention
• prognosis

Abbreviations
ACPA,	=	anti-citrullinated protein antibodies;
AFA,	=	anti-filaggrin antibodies;
AhFibA,	=	anti-human fibrin(ogen) autoantibodies;
AKA,	=	anti-keratin antibodies;
anti-CCP,	=	anti-cyclic citrullinated peptide antibodies;
anti-Sa,	=	anti-citrullinated vimentin antibodies;
anti-TNFα,	=	anti-tumor necrosis factor-α antibodies;
APF,	=	antiperinuclear factor;
CCP,	=	cyclic citrullinated peptide;
CK,	=	cytokeratin;
DMARDS,	=	disease-modifying anti-rheumatic drugs;
H2A, H3, and H4,	=	histone core proteins;
HCV,	=	hepatitis C virus;
HL-60,	=	a promyelocytic cell line;
HLA-DR,	=	human class II histocompatibility antigen;
JIA,	=	juvenile idiopathic arthritis;
MBP,	=	myelin basic protein;
MHC,	=	major histocompatibility complex;
OR,	=	odds ratio;
PAD,	=	peptidylarginine deiminase;
RA,	=	rheumatoid arthritis;
RF,	=	rheumatoid factor;
Sa,	=	citrullinated vimentin (vimentin is an intermediate filament protein);
SE,	=	shared epitope;
SLE,	=	systemic lupus erythematosus;
SNPs,	=	single nucleotide polymorphisms;
SS,	=	Sjogren syndrome

Abbreviations
ACPA,	=	anti-citrullinated protein antibodies;
AFA,	=	anti-filaggrin antibodies;
AhFibA,	=	anti-human fibrin(ogen) autoantibodies;
AKA,	=	anti-keratin antibodies;
anti-CCP,	=	anti-cyclic citrullinated peptide antibodies;
anti-Sa,	=	anti-citrullinated vimentin antibodies;
anti-TNFα,	=	anti-tumor necrosis factor-α antibodies;
APF,	=	antiperinuclear factor;
CCP,	=	cyclic citrullinated peptide;
CK,	=	cytokeratin;
DMARDS,	=	disease-modifying anti-rheumatic drugs;
H2A, H3, and H4,	=	histone core proteins;
HCV,	=	hepatitis C virus;
HL-60,	=	a promyelocytic cell line;
HLA-DR,	=	human class II histocompatibility antigen;
JIA,	=	juvenile idiopathic arthritis;
MBP,	=	myelin basic protein;
MHC,	=	major histocompatibility complex;
OR,	=	odds ratio;
PAD,	=	peptidylarginine deiminase;
RA,	=	rheumatoid arthritis;
RF,	=	rheumatoid factor;
Sa,	=	citrullinated vimentin (vimentin is an intermediate filament protein);
SE,	=	shared epitope;
SLE,	=	systemic lupus erythematosus;
SNPs,	=	single nucleotide polymorphisms;
SS,	=	Sjogren syndrome