Signs of Immune Activation and Local Inflammation Are Present in the Bronchial Tissue of Patients with Untreated Early Rheumatoid Arthritis

Gudrun Reynisdottir^1,2, Helga Olsen³, Vijay Joshua⁴, Marianne Engström², Magnus Skold³, Anders Eklund⁵, Johan Grunewald³ and Anca I Catrina², ¹Rheumatology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, ²Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, ³Department of Medicine, Division of Respiratory Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden, ⁴Unit of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, ⁵Division of Respiratory Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Anti-CCP antibodies and rheumatoid arthritis (RA), Lung Disease

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III

Session Type: ACR Poster Session C

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

Background/Purpose:

Events in the lungs might contribute to generation of anti citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in the bronchial biopsies and bronchoalveolar lavage (BAL) of early-untreated RA patients in the absence of concomitant lung pathology.

Methods: 24 RA patients with symptom duration less than one year and naïve to disease-modifying antirheumatic drugs (DMARD) were subjected to bronchoscopy where bronchoalveolar lavage (BAL) and mucosal large bronchial biopsies were retrieved. For comparison 15 bronchial biopsies and 79 BAL samples from healthy volunteers were available. Histological examination was performed to evaluate lymphocyte infiltration, presence of immune cells (T and B cells, plasma cells, dendritic cells and macrophages) and immune activation markers. Cells composition of BAL samples was analyzed by differential counting and flow cytometry.

Results:

Lymphocyte infiltration was more frequently found in ACPA-positive patients (9 out of 18 patients, 50%) as compared to ACPA-negative patients (1 our of 6, 17%, p>0.05) and controls (2 out of 15, 13%, p<0.05). Occasional formation of germinal center like structures was observed only in ACPA-positive RA patients (2 out of 18, 11%). These structures were positive for B cells markers and activation-induced cytidine deiminase and stained positively with biotinylated cit-enolase.

B cells and plasma cells were only found in ACPA-positive patients, while T cells were more frequently detected in bronchial biopsies of ACPA-positive (median 2, range 1-3) as compared to ACPA-negative (median 1, range 1-3) RA patients. Similar, expression of immune activation markers was higher in ACPA-positive as compared to ACPA-negative RA patients for both HLA-DR (median of 3, range 2-3 as compared to a median of 2, range 1-3, p<0.05) and HLA-DQ (median of 2, range 0-3 as compared to a median of 1, range 1-3, p<0.05). BAL samples of ACPA-positive but not ACPA-negative RA patients had significantly higher relative numbers of lymphocytes and expressed higher levels of activation markers compared to controls.

Conclusion:

Signs of immune cell accumulation and activation are present in the bronchial tissue of untreated early-RA patients without concomitant lung pathology, strengthening the role of the lung compartment as a critical initiating factor in the development of ACPA-positive RA.

Disclosure: G. Reynisdottir, None; H. Olsen, None; V. Joshua, None; M. Engström, None; M. Skold, None; A. Eklund, None; J. Grunewald, None; A. I. Catrina, None.

To cite this abstract in AMA style:

Reynisdottir G, Olsen H, Joshua V, Engström M, Skold M, Eklund A, Grunewald J, Catrina AI. Signs of Immune Activation and Local Inflammation Are Present in the Bronchial Tissue of Patients with Untreated Early Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/signs-of-immune-activation-and-local-inflammation-are-present-in-the-bronchial-tissue-of-patients-with-untreated-early-rheumatoid-arthritis/. Accessed .

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