Session Information
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Lung disease has been associated with elevations of RA and Sjogren’s-related autoantibodies (Abs), even in the absence
of extrathoracic features of these diseases (Fischer
2010). In particular, in classifiable RA organized ectopic lymphoid tissue in
the lung has been associated with RA related Abs (Rangel-Moreno 2006). Herein
we examine the association of Abs and lung histopathology in subjects with RA
lung disease, as well as subjects with non-RA lung disease.
Methods: Using materials from the NIH’s Lung Tissue Resource
Consortium (LTRC) we evaluated lung tissue and matched serum samples from 75
subjects with lung disease who for clinical care required lung biopsy: 10
subjects with RA and interstitial lung disease (ILD), and 65 subjects with ILD
or emphysema in absence of RA based on evaluation at the time of lung biopsy.
Serum was tested for Abs CCP3.1, RF isotypes
IgA, IgM and IgG, and SSA
and SSB. Lung tissue was evaluated by
microscopy (H&E) to determine the presence of organized ectopic lymphoid
tissue defined as germinal centers (GCs) by a pulmonary pathologist blinded to
subjects’ Ab status. Multivariate analyses were used
to determine associations of Abs and GCs.
Results: The
patients’ characteristics grouped based on the presence of GCs are presented in
the Table. RA was significantly associated with the presence of GCs, and there
was a trend towards increasing age being inversely associated with GCs; smoking
was not associated with the presence of GCs. In analyses adjusting for RA and
age, serum positivity for CCP3.1 was strongly associated with the presence of
GCs (OR 4.1, 95% CI 1.2-14.4; p=0.03). In adjusted analyses there were no
significant associations with RF’s or SSA/B with GCs as single Abs; however, an
increasing number of positive Abs was associated with GCs. Specifically, for
every increase by 1 in number of serum Abs (+), there was a 60% increase in risk
of having GCs (OR 1.6, 95% CI 1.1-2.4; p=0.03).
Conclusion: In
this unique sample set from the LTRC, we confirm a strong relationship between
serum Abs and the presence of organized ectopic lymphatic tissue/GCs in the
lung, even after adjusting for the presence of clinically apparent RA. The
strongest associations were observed for anti-CCP and increasing total number
of Abs. The findings suggest a mechanistic link between GCs in the lung and
circulating Abs, and in particular anti-CCP, that may be due to in-situ generation
of Abs within GCs in the lung or that circulating Abs perpetuate the immune
response by forming organized lymphoid tissue in the lung. Future studies
should assess these potential mechanisms as well as evaluate the potential that
Abs may be a marker for lung GCs that could be used to understand disease
prognosis and response to treatment.
|
Table. Characteristics of subjects with and without germinal centers |
|||
|
|
Germinal Center (+) N=16 |
Germinal Center (-) N=59 |
p-value |
|
Age, median (range) |
53 (40-73) |
63 (40-80) |
0.06 |
|
Female (%) |
63% |
56% |
0.78 |
|
Non-Hispanic White (%) |
75% |
78% |
0.20 |
|
Ever smoker (%) |
75% |
73% |
1.00 |
|
Rheumatoid arthritis diagnosis (%)
|
31%
|
9%
|
0.03*
|
|
Autoantibodies |
|
|
|
|
RF-IgA |
25% |
15% |
0.46 |
|
RF-IgM
|
44%
|
10%
|
<0.01*
|
|
RF-IgG
|
38% |
24% |
0.34 |
|
CCP3.1
|
56%
|
22%
|
0.01*
|
|
SSA |
13% |
7% |
0.60 |
|
SSB |
6% |
2% |
0.38 |
|
Antibody Count
|
1.5 (0-5)
|
0 (0-6)
|
<0.01*
|
|
*In analyses adjusted for age and diagnosis of RA, CCP3.1 positivity and Antibody Count were significantly associated with the presence of Germinal Centers; however, RF-IgM was not. For CCP3.1 adjusted OR 4.08, 95% CI 1.16-14.37; p=0.03. For Antibody Count adjusted OR 1.59, 95% 1.06-2.40; p=0.03.
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To cite this abstract in AMA style:
Brown LE, Demoruelle MK, Parish MC, Feser ML, Sachs PB, Heinz DE, Cool CD, Deane KD. Ectopic Lymphoid Tissue in the Lung Is Associated with Serum Rheumatoid Arthritis-Related Autoantibodies Even in Absence of Clinically Apparent Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/ectopic-lymphoid-tissue-in-the-lung-is-associated-with-serum-rheumatoid-arthritis-related-autoantibodies-even-in-absence-of-clinically-apparent-rheumatoid-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/ectopic-lymphoid-tissue-in-the-lung-is-associated-with-serum-rheumatoid-arthritis-related-autoantibodies-even-in-absence-of-clinically-apparent-rheumatoid-arthritis/