A role for anti‐BP180 autoantibodies in chronic rhinosinusitis

Abstract

Objectives CRS is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS. Study Design Case-control experimental study Methods The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time PCR, Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera. Results BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluoresence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (p<0.05). Conclusions BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS.

A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps

“…In addition, our group has previously shown that B cell-activating factor (BAFF) of the TNF family, a key B cell survival factor, is highly expressed in NP tissue from patients with CRSwNPs (8). We also reported increased levels of autoantigen-specific antibodies in NP tissue (9,10). Several reports have also demonstrated elevated levels of various isotypes of Igs, including IgG, IgE, and IgA, in sinus tissue from patients with CRS (11,12).…”

Immune Mechanisms of Chronic Rhinosinusitis

“…While we have been unable to detect an elevated presence of tertiary lymphoid structures, we have identified increased expression of the extrafollicular plasmablast marker Epstein-Barr virus-induced protein 2 (EBI2) in nasal polyps, which also supports the notion that local activation of B cells can occur in nasal polyps [50]. To date, the antigen specificity of the majority of the antibody repertoire is not known, although, IgE to S. aureus enterotoxin B and IgG and IgA to a variety of auto-antigens have been reported to be elevated [54, 55•, 56]. Whether these antibodies contribute to pathogenesis also remains unclear.…”

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

“…Tan et al (122) showed that nasal polyps contain autoantibodies that are likely responsible for activation of complement in the tissue. Among the autoantibodies described are antibodies directed against basement membrane, and the complement activation that occurs is localized at the basement membrane region (123, 124). The presence of autoantibodies in polyps may occur as a result of significant levels of the B cell–activating factor (BAFF), a cytokine that drives autoimmunity in mouse models of overexpression (125).…”