Presence of ACPA in a Large (>40.000) Population Based Cohort from the Netherlands

Elisabeth Brouwer¹, Suzanne Arends², Hendrika Bootsma¹, Caroline Roozendaal³, Pieter C Limburg⁴, Fiona Maas¹, René E. M. Toes⁵, T. W. J. Huizinga⁶, LA Trouw⁷ and Annemirthe Van Zanten¹, ¹Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, ²Rheumatology, Medical Center Leeuwarden, Leeuwarden, Netherlands, ³Laboratory Medicine, University Medical Center Groningen, Groningen, Netherlands, ⁴Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, ⁵Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ⁶Leiden University Medical Center, Leiden, Netherlands, ⁷Rheumatology, Leiden University Medical Centre, Leiden, Netherlands

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ACPA, Arthritis, Periodontitis, population studies and risk

Session Information

Date: Monday, November 9, 2015

Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Anti-citrullinated protein antibodies (ACPA) status provides important information regarding the diagnosis and prognosis of Rheumatoid Arthritis (RA). By using samples from blood bank donors that later developed RA it was shown that ACPA can already be present many years prior to the clinical onset of RA. However, little information is available on the presence of ACPA in the general population and the actual predictive power of ACPA positivity towards development of RA in the future. In this study, we determined the prevalence of ACPA in 40.227 participants from the LifeLines (LL) population based study (1).

Methods: The LifeLines cohort consists of 167.729 persons divided over 3 generations in the northern provinces of The Netherlands. Participants were recruited with help of general practitioners from both rural and non-rural areas and from different economic classes.For this cross-sectional study, 40.136 LL participants were tested for serum levels of ACPA from March 2012 until September 2013 The detection of ACPA was performed by measuring anti-CCP2 (by EliA-CCP test) on the Phadia 250 analyzer. ACPA levels ≥ 5 U/ml are considered positive. An extensive questionnaire on demographic and clinical information, including smoking, periodontal health, and early symptoms of musculoskeletal disorders was sent around as well in 2012 and 2013. RA was defined by a combination of self-reported RA, medication use (DMARDs, NSAIDs and/or steroids) for the indication of rheumatism and visiting a medical specialist within the last year. Mann-Whitney U and Chi-square tests were performed to assess differences between the ACPA positive and negative and LL participants.

Results: Of the total 40.136 individuals, 666 (1.7%) had an ACPA level ≥ 5 U/ml and 306 (0.8%) had an ACPA level ≥ 10 U/ml. Of the participants with ACPA level ≥ 5 U/ml, 14.4% had self-reported RA and 9.3% were defined as having RA.Within the group of self-reported and defined RA patients, ACPA-positivity (≥ 5 U/ml) was seen in 96 (11.5%) and 62 (44.9%) participants, respectively. In participants without self-reported/defined RA, 570 (1.5%) were ACPA positive. ACPA-positive participants reported significantly more pack years of smoking, were more often female and were significantly older compared to ACPA-negative participants (Table 1). When excluding all RA patients, differences in gender and smoking remained statistically significant, whereas age was comparable between both groups (data not shown).

Table 1 baseline characteristics of all participants
	All (n=40.136)	ACPA-positive (≥ 5 U/mL) (n=666)	ACPA-negative (n=39,470)	P-Value
Age (yrs)	44(18-92)	46(19-80)	44(18-92)	< 0.001
Gender (female)	58%	65%	58%	< 0.001
Smoking Pack years	0.00(0-139)	0.90(0-86)	0.00(0-139)	< 0.001
Smoking status never	49%	43%	49%	0.006
Smoking status former	30%	32%	30%
Smoking status current	21%	25%	21%
Self-reported RA	2.0%	14.0%	1.9%	< 0.001
Defined RA	0.3%	9.3%	0.2%	< 0.001
BMI, alcohol use, periodontitis, first degree relatives of RA patients, and in women, nulliparity, menopausal status, early menarche and regular menses were not significantly associated with ACPA status.

Conclusion: In this large population based study, the prevalence of ACPA levels ≥ 5 U/ ml as estimated by the Phadia analyzer was 1.7% for the total group and 1.5% when excluding RA patients. Smoking, female gender and older age were more frequently present in ACPA-positive LL participants.

References: 1. Scholtens S et al Int J Epidemiol. 2014 Dec 14. pii: dyu229. [Epub ahead of print]

Disclosure: E. Brouwer, Abbvie, 2,Pfizer Inc, 2; S. Arends, Pfizer Inc, 2,Abbvie, 2; H. Bootsma, Roche Pharmaceuticals, 2,Bristol-Myers Squibb, 2; C. Roozendaal, None; P. C. Limburg, None; F. Maas, None; R. E. M. Toes, None; T. W. J. Huizinga, Merck, UCB, BMS, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boehringer, Takea, Zydus, and Eli Lilly., 5,Roche & Abbott, 9; L. Trouw, None; A. Van Zanten, None.

To cite this abstract in AMA style:

Brouwer E, Arends S, Bootsma H, Roozendaal C, Limburg PC, Maas F, Toes REM, Huizinga TWJ, Trouw L, Van Zanten A. Presence of ACPA in a Large (>40.000) Population Based Cohort from the Netherlands [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/presence-of-acpa-in-a-large-40-000-population-based-cohort-from-the-netherlands/. Accessed .

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