Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis-associated nonspecific interstitial pneumonia and usual interstitial pneumonia

Abstract

Objective: B lymphocytes are emerging as important elements in the events leading to joint destruction in rheumatoid arthritis (RA). However, B lymphocytes have not been studied in rheumatoid arthritis (RA)-associated lung disease. We performed a morphologic and quantitative analysis of B lymphocytes and plasma cells in RA-associated interstitial pneumonia (IP) in comparison with idiopathic IP and normal lungs.

Methods: Open-lung biopsy specimens from patients with RA-associated IP (n = 18), patients with idiopathic IP (n = 21), and control subjects (n = 11) were stained with antibodies to CD20 and CD138. Morphologic patterns of stained specimens were characterized and staining was quantified using computer-assisted image analysis.

Results: In RA-associated IP, marked follicular B cell hyperplasia was detected, which was limited almost entirely to peribronchiolar lymphoid aggregates. Plasma cells were also present in large numbers, but showed a more diffuse tissue infiltration. Quantification of B cells demonstrated higher cellularity in RA-associated IP (median 2.0%, interquartile range [IQR] 1.0-5.7) as compared with idiopathic IP (0.9%, IQR 0.5-2.1). Control specimens showed a significantly smaller number of B cells compared with both diseases (0.4%, IQR 0.1-1.3). In RA patients who were smokers and in those who were male, the proportion of CD20+ tissue areas further increased to 4.3% (IQR 1.0-5.8) and 3.9% (IQR 0.7-6.9), respectively.

Conclusion: We demonstrated a significant follicular B cell hyperplasia in RA-associated IP. The differences between RA-associated IP and idiopathic IP imply a differential emphasis of B cell-mediated mechanisms in the 2 diseases despite radiologic and histologic similarities and provide a rationale for studying functional aspects of B cell involvement in the pathogenesis of RA-associated IP.