[CITATION][C] B cell infiltration in systemic sclerosis–associated interstitial lung disease

R Lafyatis, C O'Hara… - … : Official Journal of …, 2007 - Wiley Online Library
R Lafyatis, C O'Hara, CA Feghali‐Bostwick, E Matteson
Arthritis & Rheumatism: Official Journal of the American College …, 2007Wiley Online Library
Rituximab has shown efficacy for the treatment of rheumatoid arthritis (RA) and is currently
under study in systemic lupus erythematosus and a variety of other rheumatic diseases (1–
3). This monoclonal antibody to CD20 depletes peripheral B cells, but the mechanism of its
therapeutic effect is uncertain (4, 5). Findings of several studies have suggested the
potential importance of B cells in systemic sclerosis (SSc). Levels of circulating naive B cells
are increased in SSc patients, while memory B cells, although reduced in number, show …
Rituximab has shown efficacy for the treatment of rheumatoid arthritis (RA) and is currently under study in systemic lupus erythematosus and a variety of other rheumatic diseases (1–3). This monoclonal antibody to CD20 depletes peripheral B cells, but the mechanism of its therapeutic effect is uncertain (4, 5). Findings of several studies have suggested the potential importance of B cells in systemic sclerosis (SSc). Levels of circulating naive B cells are increased in SSc patients, while memory B cells, although reduced in number, show markers of activation (6). Both B cell populations exhibit increased expression of CD19, an important regulator of B cell maturation (6). Findings in studies of mice have complemented these observations (7), suggesting that B cells might play an important role in fibrotic disease. In addition, microarray results demonstrating a prominent immunoglobulin signature in the skin of patients with SSc (8) and the results of studies of rituximab treatment in other rheumatic diseases have led to increased interest in these cells. The presence of infiltrating B cells in the skin of patients with SSc (8) provided additional motivation for our current, ongoing open-label study of rituximab for SSc skin disease. Interstitial lung disease (ILD) is a grave complication of SSc, leading to significant morbidity and mortality (9). Treatment options are extremely limited, with cyclophosphamide as the only therapy that has shown some, albeit modest, efficacy (10). ILD occasionally complicates RA, and recent histopathologic studies of affected lung tissue from RA patients have revealed variable degrees of B cell infiltration (11). To better understand the potential importance of B cells in SSc-associated pulmonary disease, we studied B cell infiltration in stored tissue specimens from patients with SScassociated ILD.
Pulmonary tissue samples from 11 patients with SScassociated ILD (4 with nonspecific interstitial pneumonitis [NSIP], 7 with usual interstitial pneumonitis [UIP]) were stained for CD20 (a marker of mature B cells and the target of the monoclonal antibody rituximab), CD3 (a marker of T cells), and CD68 (a marker of macrophages). B cell infiltration was a prominent finding in many of the specimens. B cells were frequently found arranged in lymphoid aggregates (Figures 1a, h, and i), but were also seen in a more diffuse pattern (Figure 1d). T cells were also found, in both lymphocyte aggregates and more diffuse lymphocyte infiltrates (Figures 1b and e). Most lymphocyte aggregates lacked macrophages (results not shown), but macrophages were commonly seen in intraalveolar and interstitial spaces (Figures 1c and f). B cell infiltration in the specimens was assessed by counting the number of B cells/high-power field (400 total magnification), with the observer blinded with regard to the biopsy classification. Biopsy samples were not counterstained, to lessen the likelihood of the reader being influenced by the histopathologic diagnosis. Examples of staining are shown in Figures 1h and i. Specimens from patients with each of the two primary pulmonary pathologic subtypes (UIP and NSIP) showed variable, but some striking, degrees of B cell staining
Wiley Online Library