ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 525

Association Between Fine Specificity of Anti-Citrullinated Peptide Antibodies and High Resolution Computed Tomography Parenchymal Lung Changes in Patients with Early RA

Vijay Joshua1, Katerina Chatzidionysiou1, Gudrun Reynisdottir1, Aase Haj Hensvold1, Linda Mathsson-Alm2, Monika Hansson3, Leonor Nogueira4, Anders Eklund5, Guy Serre4, Johan Grunewald5 and Anca I Catrina6, 1Rheumatology Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden, Stockholm, Sweden, 2ThermoFisher Scientific, Uppsala, Sweden, Uppsala, Sweden, 3Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 4Unité Différenciation Épidermique et Autoimmunité Rhumatoïde, Unité Mixte de Recherche, INSERM,Toulouse, France, Toulouse, France, 5Division of Respiratory Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, Stockholm, Sweden, 6Unit of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords:

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

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

Background/Purpose:

We previously showed that anti-CCP2 antibodies are associated with parenchymal lung abnormalities in patients with early RA1. This study aims to examine the association between ACPA fine specificities and parenchymal lung changes in an early RA cohort. 

Methods:  

Patients with newly diagnosed RA according to the ACR 1987 classification criteria and naïve to treatment with oral glucocorticoids or DMARDs were eligible for the study. High-resolution computed tomography (HRCT) was performed in order to assess the presence of parenchymal lung changes (ground glass changes, nodules, infiltrates or fibrosis). ImmunoCAP was used to detect RF IgA, RF IgM, anti-CCP2 IgA, anti-CCP2 IgG and ISAC microarray system2was used to detect antibodies against 10 citrullinated (Cit) peptidic antigens: CCP-1 (Filaggrin), CEP-1 (α-enolase), Vim 2-17, Vim 60-75 (Vimentin), Fib β 36-52, Fib α 573, Fib α 591, Fib α 36-50, Fib β 60-74, Fib α 621-635 (Fibrinogen).

Logistic regression analysis was performed to examine possible associations between parenchymal lung changes at the time of RA diagnosis and autoantibodies, adjusted for age and sex. Due to the potential risk for effect modification of smoking and the strong association between smoking and Cit peptides, we stratified the cohort according to ever vs. never smokers. 

Results:

A total of 106 patients with available HRCT were included in the analysis. The mean (SD) age was 57 (14) years. The majority were females (69%); 73% were ever smokers while 29% were current smokers; 70% were positive for RF and 69% were positive for anti-CCP2. Parenchymal lung changes were found in 58 patients (54.7%). Higher age, RF IgA, CCP2 IgG, ever smoking and pack-years above 24 were significant predictors of parenchymal lung changes (table 1). Some ACPA fine specificities, especially against Cit Fib and Cit Vim peptides, were associated to parenchymal lung changes in ever smokers (table 2). The risk of having parenchymal changes increased parallel to the increase of the number of ACPA specificities (table 2). Having five or more ACPA specificities at the time of diagnosis increased the risk of having lung abnormalities in ever smokers by 6.6 times (OR=5.8, 95% CI=1.6-27.3). 

Conclusion:

The presence of RF IgA, anti-CCP2 IgG, antibodies to Cit Fib and Cit Vim peptides were strongly associated to parenchymal lung changes in ever smokers with early RA. The more ACPA fine specificities, the higher the risk of having parenchymal lung changes at the time of RA diagnosis.

  1. Reynisdottir G, et al., Arthritis Rheumatol 2014
  2. Hansson M, et al., Arthritis Res Ther 2012 

Variable

OR (95% CI)

P-value

Age

1.0 (1.0-1.1)

0.006

Age (≥65 vs. < 65)

2.5 (1.1-5.9)

0.03

Sex (Male vs. Female)

1.7 (0.7-4.0)

0.22

RF                   Any

                       IgM

                        IgA

2.0 (0.8-4.5)

2.0 (0.8-4.5)

2.7 (1.2-5.9)

0.12

0.12

0.02

Anti-CCP2       Any

                        IgG

                       IgA                      

2.6 (1.1-6.0)

2.3 (1.0-5.4)

1.5 (0.7-3.6)

0.03

0.05

0.32

Bone erosions

1.1 (0.4-2.8)

0.84

Smoking ( % ever)

2.6 (1.1-6.2)

0.04

Smoking (% current)

1.8 (0.7-4.2)

0.20

Pack-years (median (IQR))

1.1 (1.0-1.1)

0.001

Pack-years  1-11 vs. 0

                     12-23 vs. 0

                      ≥ 24 vs, 0

1.3 (0.4-3.8)

2.2 (0.8-6.6)

6.9 (2.0-23.5)

0.69

0.15

0.002

Table 1.Predictors of parenchymal lung abnormalities at the time of RA diagnosis in patients with early RA (symptoms duration < 1 year).

Non-smokers [N=29]

Ever smokers [N=77]

OR (95% CI)

P-value

OR (95% CI)

P-value

Any CCP2

       CCP2 IgG

       CCP2 IgA

7.4 (0.6-86.6)

7.4 (0.6-86.6)

1.1 (0.1-9.7)

0.11

0.11

0.91

5.0 (1.5-16.2)

4.2 (1.3-13.2)

1.6 (0.6-4.5)

0.007

0.01

0.38

Any RF

        RF IgA

        RF IgM

2.6 (0.4-17.7)

1.4 (0.2-7.6)

2.6 (0.4-17.7)

0.32

0.73

0.32

2.6 (0.9-7.6)

4.7 (1.6-13.7)

2.6 (0.9-7.6)

0.09

0.004

0.09

Cit Fibrinogen peptides

     Fib  β 36-52 cit

     Fib  α 573 cit

     Fib  α 612-635 cit

     Fib  β 60-74 cit

     Fib  α 36-50 cit

     Fib   α 591 cit

2.3 (0.4-13.1)

1.1 (0.2-5.9)

2.3 (0.4-13.0)

2.0 (0.2-14.3)

4.6 (0.7-28.3)

2.7 (0.4-15.8)

0.6 (0.04-8.4)

0.35

0.87

0.35

0.47

0.10

0.29

0.67

3.0 (1.0-8.8)

2.7 (0.9-7.6)

3.9 (1.3-12.5)

2.2 (0.8-6.4)

2.2 (0.8-6.5)

1.2 (0.4-3.6)

1.4 (0.4-4.7)

0.05

0.07

0.02

0.16

0.14

0.80

0.60

Cit Vimentin Peptides

     Vim 2-17 cit

     Vim 60-75 cit

3.5 (0.5-24.9)

1.2 (0.2-6.5)

4.9 (0.7-32.7)

0.22

0.80

0.10

2.9 (1.0-8.5)

2.9 (1.0-8.6)

2.2 (0.8-6.3)

0.06

0.05

0.15

CEP-1 (α-enolase)

0.4 (0.06-2.4)

0.30

2.0 (0.7-6.0)

0.20

N. ACPAs    0 (ref)

                 1-4

                 > 4

2.6 (1.9-35.9)

3.6 (0.3-44.7)

0.47

0.32

5.2 (1.3-21.2)

6.6 (1.6-27.3)

0.02

0.009

Table 2. Association between rheumatoid factor (RF), anti-CCP and ACPA fine specificities according to smoking status (never smokers and ever smokers), as assessed by logistic regression adjusted for age and sex. (All ACPA fine specificities were analyzed but not shown in the table). 

Disclosure: V. Joshua, None; K. Chatzidionysiou, None; G. Reynisdottir, None; A. H. Hensvold, None; L. Mathsson-Alm, None; M. Hansson, None; L. Nogueira, None; A. Eklund, None; G. Serre, None; J. Grunewald, None; A. I. Catrina, None.

To cite this abstract in AMA style:

Joshua V, Chatzidionysiou K, Reynisdottir G, Hensvold AH, Mathsson-Alm L, Hansson M, Nogueira L, Eklund A, Serre G, Grunewald J, Catrina AI. Association Between Fine Specificity of Anti-Citrullinated Peptide Antibodies and High Resolution Computed Tomography Parenchymal Lung Changes in Patients with Early RA [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/association-between-fine-specificity-of-anti-citrullinated-peptide-antibodies-and-high-resolution-computed-tomography-parenchymal-lung-changes-in-patients-with-early-ra/. Accessed .

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