Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps

Background: Chronic rhinosinusitis (CRS) with nasal polyps is an inflammatory condition of the nasal passage and paranasal sinuses characterized by T_H2-biased inflammation with increased levels of B-cell activating factor of the TNF family (BAFF), B lymphocytes, and immunoglobulins. Because high levels of BAFF are associated with autoimmune diseases, we assessed for evidence of autoimmunity in patients with CRS. Objectives: The objective of this study was to investigate the presence of autoantibodies in sinonasal tissue from patients with CRS. Methods: Standardized nasal tissue specimens were collected from patients with CRS and control subjects and assayed for immunoglobulin production, autoantibody levels, tissue distribution of immunoglobulins, and binding potential of antibodies in nasal tissue with a multiplexed autoantibody microarray, ELISA, and immunofluorescence. Results: Increased levels of several specific autoantibodies were found in nasal polyp tissue in comparison with levels seen in control tissue and inflamed tissue from patients with CRS without nasal polyps (P <.05). In particular, nuclear-targeted autoantibodies, such as anti-dsDNA IgG and IgA antibodies, were found at increased levels in nasal polyps (P <.05) and particularly in nasal polyps from patients requiring revision surgery for recurrence. Direct immunofluorescence staining demonstrated diffuse epithelial and subepithelial deposition of IgG and increased numbers of IgA-secreting plasma cells not seen in control nasal tissue. Conclusions: Autoantibodies, particularly those against nuclear antigens, are present at locally increased levels in nasal polyps. The presence of autoantibodies suggests that the microenvironment of a nasal polyp promotes the expansion of self-reactive B-cell clones. Although the pathogenicity of these antibodies remains to be elucidated, the presence of increased anti-dsDNA antibody levels is associated with a clinically more aggressive form of CRS with nasal polyps requiring repeated surgery.