Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Anti-CCP Positivity in Patients with Lung Disease but No Apparent Articular RA: A Pre-RA State?

Solomon1,  Joshua J., Stevens1,  Allen, Gill1,  Mary, Brandorff1,  Jennifer, Swigris1,  Jeffrey J., Deane2,  Kevin, Martin1,  Richard

National Jewish Health
University of Colorado

Background and Objectives:

Anti-CCP positivity is highly specific for RA, and can be identified in patients prior to the development of articular manifestations of RA. Also, lung disease may be the initial clinical manifestation of RA, and as such patients with lung disease but no articular RA may have anti-CCP positivity, reflecting early RA-related immune dysregulation. For this study, we sought to identify and describe a patient cohort characterized by lung disease, with moderate-to-high anti-CCP positivity, in the absence of articular manifestations of RA.

Methods:

Between January 2008 and January 2010, 2393 patients had an anti-CCP antibody test at our center using the INOVA CCP3.1 IgG/IgA ELISA kit. 312 patients had a positive anti-CCP (>= 20 IU). Of these, we excluded those with a low-titer positive anti-CCP (20 IU–39 IU) (n=63), patients in whom the anti-CCP was assessed due to joint disease (either with a pre-existing diagnosis of RA, or due to presence of joint symptoms of inflammation or synovitis on examination as determined by the treating physician) (n=214), patients younger than 18 (n=1), those without lung disease (n=2) and all patients with other defined connective tissue diseases (CTD) (n=8). Thus, the study cohort was comprised of 52 patients with a positive anti-CCP of at least moderate titer (>= 40 IU) along with symptoms of respiratory impairment—without a prior diagnosis of RA, any other CTD, or presence of joint inflammation at initial testing for anti-CCP. All data were extracted by retrospective chart review.

Results:

Clinical characteristics of anti-CCP positive subjects with lung disease
Number of patients52
Median follow-up duration (d)458 (114–755)
Median age (y)68 (36–84)
Male gender22 (42%)
Smokers-Past29 (57%)
Smokers-Current0 (0)
First degree relative with RA7 (17.5%)
Dyspnea/cough at presentation52 (100%)
Synovitis by history or exam at presentation0 (0%)
Median anti-CCP (IU)86.5 (40–235)
RF positivity18 (37%)
Median RF (IU)148 (20–3650)
Development of articular RA during follow-up1 (2%)
High-Resolution Computed Tomographic Findings
Airways disease17 (33%)
Parenchymal lung disease18 (35%)
Airways + Parenchymal disease13 (24%)
*Miscellaneous patterns4 (8%)
*Includes one each of emphysema, vasculitis, sarcoidosis, and non-tuberculous mycobacterial infection

Conclusions:

We have identified a cohort of patients, predominately former smokers, with lung disease, a moderate-to-high positive anti-CCP and no articular manifestations of RA. Within a median follow-up of 15 months, 2% of this cohort has already developed inflammatory arthritis. These findings suggest i) the lung is the site of initial RA-related immune dysregulation, and that such patients represent a 'pre-articular RA' phenotype, ii) the lung in some cases is a pre-articular target of RA-related autoimmunity, or iii) in cases who never develop articular RA, anti-CCP generation may be a non-RA specific immune response, or that some factor prevents these patients from later developing RA-related articular disease. Prospective assessments of this unique cohort should help further our understanding of the etio-pathogenesis of RA.

To cite this abstract, please use the following information:
Solomon, Joshua J., Stevens, Allen, Gill, Mary, Brandorff, Jennifer, Swigris, Jeffrey J., Deane, Kevin, et al; Anti-CCP Positivity in Patients with Lung Disease but No Apparent Articular RA: A Pre-RA State? [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2119
DOI: 10.1002/art.29883

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