Anti-citrullinated protein antibody positive rheumatoid arthritis is primarily determined by rheumatoid factor titre and the shared epitope rather than smoking per se

Background:In the idividuals with genetic and enviromental risk factors, immune events at mucosal surfaces occur and may precede systemic autoimmunity. Anti-citrullinated protein antibodies (ACPA) are present in the serum for an average of 3-5 years prior to the onset of rheumatoid arthritis (RA) during an asymptomatic period. In ACPA-positivite individuals, the additional presence of RA-related risk factors appears to add significant power for the development of RA. To date, there have been few reports in which clinical courses of ACPA-positive asymptomatic individuals were investigated prospectively.Objectives:To observe the clinical time course of ACPA-positive healthy population for the development of RA.Methods:Healthy volunteers without joint pain or stiffness, who attended the comprehensive health screening of our hospital, were enrolled in this prospective observational study. The serum ACPA levels were quantified by Ig-G anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay with levels > 4.4 U/mL considered positive. ACPA-positive subjects were followed by rheumatologists of our department clinically or a questionnaire sent by mail for screening to detect arthritis.Results:5,971 healthy individuals without joint symptons were included. Ninty-two (1.5%) were positive for ACPA. Of these, 19 (20.7%) developed RA and two were suspected as RA by mail questionnaire. Their average age were 58-years, and women were 68%. The average duration between the date of serum sampling and diagnosis was 10.7 months. ACPA-positive individuals who developed to RA had higher serum ACPA and Ig-M rheumatoid factor levels than ACPA-positive individuals who did not (P value by Mann-Whitney U test: 0.002, 0.005, respectively).Conclusion:Among ACPA-positive asymptomatic individuals, 20% developed RA. The higher titer of ACPA and Ig-M rheumatoid factor levels are risk factors for devoloping RA.Disclosure of Interests:None declared

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Comparative Utility of Anti-Citrullinated Protein Antibodies Verses Rheumatoid Factor in the Management of Rheumatoid Arthritis

MOJ Orthopedics & Rheumatology ◽

10.15406/mojor.2017.08.00323 ◽

2017 ◽

Vol 8 (4) ◽

Author(s):

Anjali Patwardhan

Keyword(s):

Rheumatoid Arthritis ◽

Rheumatoid Factor ◽

Citrullinated Protein

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Antibodies toPorphyromonas gingivalisAre Associated with Anticitrullinated Protein Antibodies in Patients with Rheumatoid Arthritis and Their Relatives

The Journal of Rheumatology ◽

10.3899/jrheum.091323 ◽

2010 ◽

Vol 37 (6) ◽

pp. 1105-1112 ◽

Cited By ~ 144

Author(s):

CAROL A. HITCHON ◽

FATIHA CHANDAD ◽

ELIZABETH D. FERUCCI ◽

ANNEMIEK WILLEMZE ◽

ANDREEA IOAN-FACSINAY ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Immune Responses ◽

Rheumatoid Factor ◽

Porphyromonas Gingivalis ◽

Immune Tolerance ◽

Oral Hygiene ◽

Shared Epitope ◽

Poor Oral Hygiene ◽

Citrullinated Peptide ◽

Anticitrullinated Protein Antibodies

Objective.Anticitrullinated protein antibodies (ACPA) are relatively specific for rheumatoid arthritis (RA), and predate disease. The oral pathogenPorphyromonas gingivalismay play a role in breaking immune tolerance to citrullinated antigens. We studied a cohort of patients with RA and their relatives looking for associations between anti-P. gingivalisantibodies and ACPA.Methods.Patients with RA (n = 82) and their relatives (n = 205) from a North American Native (NAN) population were studied, along with 47 NAN and 60 non-NAN controls. IgM and IgA rheumatoid factor (RF) were tested by nephelometry and ELISA. Second-generation anticyclic citrullinated peptide (anti-CCP2) isotypes and IgG anti-P. gingivalislipopolysaccharides were tested by ELISA. HLA-DRB1 typing was performed by sequencing. Oral hygiene and smoking habits were assessed by questionnaires.Results.Autoantibody frequency in patients with RA and relatives: ACPA 91% vs 19%, respectively; IgM RF 82% vs 17%; IgA RF 48% vs 22%. Anti-P. gingivalislevels were higher in patients with RA compared to relatives and controls (p = 0.005) and higher in ACPA-positive patients with RA than in ACPA-negative patients with RA (p = 0.04) and relatives (p < 0.001), but comparable in RF-positive and RF-negative patients and relatives. Poor oral hygiene and smoking were prevalent, but with no clear association with autoantibodies. Relatives with 2 shared-epitope alleles were more likely to be ACPA-positive (OR 2.5, p = 0.02).Conclusion.In a genetically predisposed population of NAN patients with RA and their relatives, anti-P. gingivalisantibodies were associated with ACPA. These findings suggest that immune responses toP. gingivalismay be involved in breaking immune tolerance to citrullinated antigens.

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