Lymphocyte Distribution in Biopsies of Interstitial Lung Disease Predicts Response to Monoclonal Antibody Therapy.
Michael A Seidman, Robert F Padera, Paul F Dellaripa, Lynette M Sholl. Brigham & Women's Hospital, Boston, MA
Background: Interstitial lung disease (ILD) is a heterogeneous collection of illnesses associated with inflammatory and fibrotic changes within interalveolar spaces. The etiologies of ILD include idiopathic (such as usual interstitial pneumonia, or UIP) or those related to underlying autoimmune diseases where there may be significant inflammation; of this latter set, some cases have been associated with increased B cells in lung tissue. Generalized immunosuppression is the mainstay of therapy in autoimmune ILD, but these agents have variable efficacy and significant side effects. As such, more targeted agents, such as the monoclonal antibody directed against CD20, rituximab, are under investigation for use in these populations.
Design: H&E slides were examined from surgical lung biopsies obtained from patients with ILD being treated with rituximab (two or four doses of 1000 mg). In each, histologic features, including diagnosis, degree of inflammation, and proportion of B-cells and T-cells present, were correlated with response to therapy as determined by pulmonary function testing and clinical assessment.
Results: A total of seven cases were examined. Histologically, three cases showed follicular bronchiolitis (FB), two cases showed UIP, and two cases showed nonspecific interstitial pneumonia (NSIP). In all cases, we observed an excess of CD20-positive cells (indicated by germinal center formation; quantitatively 6-48 lymphoid follicles per cm2 and 2-to-10-fold CD20 over CD3). Of these, one has just initiated therapy and follow-up is pending, while the others have all shown clinical stabilization or improvement while taking rituximab (mean follow-up 20 months, range 5-30 months).
|FB||Sjogren's||at least 2:1||unknown||improved|