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Abstract Number: 486

Anti-Citrullinated Protein Antibody Reactivities in Treatment NaïVe Early Rheumatoid Arthritis

Maria K. Jonsson1,2, Aase Hensvold3, Monika Hansson4, Linda Mathsson-Alm5, Anna-Birgitte Aga2, Joseph Sexton2, Bjørg-Tilde Fevang1,6, Siri Lillegraven2, Anca I. Catrina3 and Espen A. Haavardsholm2,7, 1Dept. of Rheumatology, Haukeland University Hospital, Bergen, Norway, 2Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 3Karolinska Institute, Stockholm, Sweden, 4Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, 5Thermo Fisher Scientific, Uppsala, Sweden, 6Dept. of Clinical Science, University of Bergen, Bergen, Norway, 7University of Oslo, Oslo, Norway

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: anti-citrullinated protein/peptide antibodies (ACPA) and biomarkers, Early Rheumatoid Arthritis

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Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: Anti-citrullinated protein antibody (ACPA) reactivities can precede RA onset, and may be involved in the pathogenesis of the disease. We wanted to assess the prevalence of baseline ACPA reactivities in an inception cohort of early RA patients, including subgroups based on anti-CCP/RF status, and to compare the findings to healthy controls.

Methods: 217 DMARD-naïve early RA patients from the ARCTIC trial (1) were analyzed. Radiographs were scored according to van der Heijde Sharp (vdHS) score. Anti-CCP status was analyzed by FEIA (positive if ≥10 IU/mL) and RF by ELISA (positive if ≥25 IU/mL). ACPA titres (AU/ml) were considered positive if above the 98-percentile of values in 619 non-RA subjects. Analysis of 13 ACPA reactivities targeting citrullinated peptides from fibrinogen, alpha-1 enolase, vimentin, fillagrin and histone was performed at baseline in patients and 94 controls (blood donors matched for age/gender/smoking), using a multiplex chip-based assay (2). Positivity and median number of ACPA reactivities in the subgroups were compared using Chi-square test and Mann-Whitney U-test, respectively. 

 

Results: Baseline characteristics are presented in the table. The median [IQR] number of antibody reactivities in all patients was 7[3,10], compared to 0[0,0] in controls (p<0.001, figure). The corresponding numbers were 8[5,10] and 0[0,1] for the anti-CCP+ vs. anti-CCP- patients (p<0.0001), 8[5,10] and 2[0,8] for the RF+ vs. RF- patients (p<0.001), and 8[6,10] and 0[0,1] for the anti-CCP+/RF+ vs. the anti-CCP-/RF- (p<0.001) (table, figure). Positivity for ACPA reactivities was seen mainly in the anti-CCP+, RF+ and anti-CCP+/RF+ patients, but also occurred more frequently in the anti-CCP-, RF- and anti-CCP-/RF- patients than in controls (anti-CCP- vs controls p=0.002, RF- vs controls p<0.001, and anti-CCP-/RF- vs. controls p=0.035) (table).

Table: Baseline characteristics

 

Anti-CCP+

n=178

Anti-CCP-

n=39

RF+

n=154

RF-

n=63

Anti-CCP+/RF+

n=147

Anti-

CCP-/RF- n=32

All RA

n=217

Control

n=94

Age, years1

50.8(13.2)

55.0(14.9)

51.9(13.3)

50.8(14.2)

51.7(13.6)

55.0(16.1)

51.5(13.6)

52(9.4)

Female2

109(61)

22(56)

91(59)

40(63)

86(59)

17(53)

131(60)

63(59)

Ever-smoker2

122(69)

26(67)

109(71)

39(62)

103(70)

20(62)

148(68)

81(64)

DAS1

3.4(1.1)

4.0(1.3)

3.5(1.2)

3.5(1.2)

3.42(1.13)

3.9(1.2)

3.5(1.2)

NA

vdHS score3

4[1.5,7.9]

4.5[2,10]

4.5[2,8]

3.5[1.5,9.8]

4.5[2,8]

5.5[1.9,12.6]

4 [1.5,8]

NA

Vim 60-75cit4

152(85)

7(18)

130(84)

29(46)

128(87)

5(16)

159(73)

5(5)

H4 31-50cit4

142(80)

3(8)

119(77)

26(41)

118(80)

2(6)

145(67)

1(1)

CEP14

137(77)

3(8)

117(76)

23(37)

115(78)

1(3)

140(65)

1(1)

Fil 307-324cit4

134(75)

2(5)

113(73)

23(37)

112(76)

1(3)

136(63)

0(0)

Fib 573cit4

121(68)

2(5)

99(64)

24(38)

99(67)

2(6)

123(57)

0(0)

Fib 36-52cit4

116(65)

1(3)

96(62)

21(33)

96(65)

1(3)

117(54)

2(2)

H3 1-30cit4

106(60)

1(3)

93(60)

14(22)

92(63)

0(0)

107(49)

0(0)

H4 14-34cit4

103(58)

2(5)

90(58)

15(24)

88(60)

0(0)

105(48)

3(3)

H3 21-44cit4

94(53)

2(5)

80(52)

16(25)

79(54)

1(3)

96(44)

1(1)

Vim 2-17cit4

87(49)

1(3)

80(52)

8(13)

79(54)

0(0)

88(41)

0(0)

Fib 591cit4

66(37)

3(8)

56(36)

13(21)

55(37)

2(6)

69(32)

1(1)

Fib 74cit4

60(34)

6(15)

54(35)

12(19)

51(35)

3(9)

66(30)

3(3)

Fib 72cit4

24(13)

3(8)

21(14)

6(1)

20(14)

2(6)

27(12)

2(2)

Number of ACPA reactivities3

8[5,10]

0[0,1]

8[5,10]

2[0,8]

8[6,10]

0[0,1]

7[3,10]

0[0,0]

1Mean(SD), 2n(%), 3median[IQR], 4n positive(%)

 

 

Figure: Number of ACPA reactivities per patient

 

 

Conclusion: Prevalence of ACPA reactivities differed in subgroups of DMARD-naïve early RA patients according to anti-CCP and RF status. In general, higher numbers of ACPA reactivities were seen in anti-CCP+ patients, but all RA subgroups, including anti-CCP-, RF- and anti-CCP-/RF- patients, had higher prevalence of ACPA reactivities compared to healthy controls.

References: 1) Haavardsholm et al BMJ 2016, 2) Hansson et al Arthr Res Ther 2012


Disclosure: M. K. Jonsson, None; A. Hensvold, None; M. Hansson, None; L. Mathsson-Alm, Thermo-Fisher Scientific, 3; A. B. Aga, None; J. Sexton, None; B. T. Fevang, Novartis Pharmaceutical Corporation, 2; S. Lillegraven, None; A. I. Catrina, None; E. A. Haavardsholm, AbbVie, Pfizer, Roche, Eli Lilly, Celgene, UCB, 5,AbbVie, Pfizer, Roche, MSD, UCB, 2,AbbVie, Pfizer, Roche, Eli Lilly, Celgene, UCB, 8.

To cite this abstract in AMA style:

Jonsson MK, Hensvold A, Hansson M, Mathsson-Alm L, Aga AB, Sexton J, Fevang BT, Lillegraven S, Catrina AI, Haavardsholm EA. Anti-Citrullinated Protein Antibody Reactivities in Treatment NaïVe Early Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/anti-citrullinated-protein-antibody-reactivities-in-treatment-naive-early-rheumatoid-arthritis/. Accessed .
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