Table 1.

Comparison of the characteristics and clinical significances between rheumatoid factors, anti-citrullinated protein antibodies and anti-carbamylated protein antibodies.

	Rheumatoid Factor	Anti-Citrullinated Protein Antibodies	Anti-Carbamylated Protein Antibodies
Year of Discovery	1940s	1964	2011
Characteristics of the Autoantibody
Antigenic Targets	-target the antigenic epitopes within the Fc region (CH2 and CH3) of IgG -conformation changes may be required for epitope exposure	-react with a variety of citrullinated antigens -partially cross-react with peptides undergone carbamylation and acetylation	-react with a variety of carbamylated antigens, homocitrulline -partially cross-react with peptides undergone citrullination
Isotypes	-IgM > IgG > IgA	-mainly IgG and IgA	-mainly IgG and IgA
Characteristics	-limited N-glycosylation -limited somatic hypermutations -limited class switching	-extensive N-glycosylation -extensive somatic hypermutations -extensive class switching	-extensive class switching -limited avidity maturation
Clinical Significance
Role in RA Diagnosis	-included in the 1987 ACR classification criteria for RA -included in the 2010 ACR/EULAR RA classification criteria	-included in the 2010 ACR/EULAR RA classification criteria	-not included in any RA classification criteria -potentially beneficial for those negative of RF and ACPA
Sensitivity for RA	-RF: 41–66% for early RA and 62–87% for RA	-ACPA: 41–66% for early RA and 41–77% for RA -double positive: 33–57% for RA	-anti-CarP Ab: 18–26% prior to and 27–46% after RA diagnosis -triple positivity: 11–39%
Specificity for RA	-RF: 43–96% for RA	-ACPA: 88–98% for RA -double positive: 91–99%	-anti-CarP Ab: 93–97% for RA -triple positivity: 98–100%
Other Conditions with Increased Antibody Titer	-other autoimmune diseases -chronic infections/inflammations -aging -smoking	-mucosal dysbiosis -tobacco smoking -other autoimmune diseases	-renal diseases -chronic inflammations -cardiovascular disease -other autoimmune diseases
Clinical Presentations	-more extraarticular manifestations -aggressive and erosive joint disease	-more severe structural damage, radiographic progression and poorer response to therapy	-more severe joint damage in those negative for ACPA
Treatment Response	-the level of RF parallels the decrease of disease activity -RF positivity possibly predicts better clinical response in those receiving rituximab and tocilizumab	-aggressive treatment with higher MTX dosing or triple therapy may be beneficial for ACPA RA -ACPA positivity cases possibly response to tocilizumab, rituximab, abatacept and tofacitinib better than those negative of ACPA	-Abatacept seem beneficial for those positive for anti-CarP Ab

RA, rheumatoid arthritis; RF, rheumatoid factors; ACPA, Anti-citrullinated protein antibody; anti-CarP Ab, Anti-carbamylated protein antibody; ACR, American College of Rheumatology; EULAR, European League Against Rheumatism; MTX, Methotrexate; Fc-crystallizable fragment.