The role of heat shock protein 27 in bronchiolitis obliterans syndrome after lung transplantation

Abstract

Background: Heat shock proteins (Hsps) are a family of evolutionary conserved proteins classified according to their size as small and large Hsps. They have a cytoprotective role and have been shown to be immunogenic molecules. In addition, self-reactivity to Hsps has been implicated in various autoimmune diseases and in the development of alloimmunity. This study examined the relationship of large and small Hsps and anti-Hsp antibodies in lung transplant (LTx) recipients who have bronchiolitis obliterans syndrome (BOS).

Methods: Anti-Hsp27 and Hsp70 antibodies, and Hsp27, Hsp60, and Hsp70 protein expression levels were evaluated in serum and bronchoalveolar lavage samples collected from 8 LTx recipients with established BOS and 8 recipients without BOS (controls). Serum from 8 healthy individuals was examined for Hsp levels as a comparison.

Results: Elevated serum Hsp27 levels were observed in recipients with BOS compared with controls or healthy individuals, whereas Hsp70 and Hsp60 expression showed no difference. Anti-Hsp27 antibody levels were significantly higher in the BAL of recipients with BOS than in those without BOS. In contrast, anti-Hsp70 antibodies levels in serum or BAL showed no difference between groups.

Conclusions: These results support the novel concept that Hsp27, but not the classic Hsp60 and Hsp70, may be associated with the development BOS. The expression of anti-Hsp27 antibodies found only in the BAL fluid suggests a local response occurring at the level of the alveoli and terminal airways.

Figure 1

Hsp expression in lung transplantation recipients with BOS, without BOS (Controls), and normal volunteers. A. Serum Hsp27 (ANOVA p-value = 0.042) B. BAL Hsp27 C. Serum Hsp60 D. BAL Hsp60 E. Serum Hsp70 F. BAL Hsp70

Figure 2

Hsp27 and Hsp70 antibodies of lung transplantation recipients with BOS, without BOS (Controls), and normal volunteers. A. Serum Anti-Hsp27 (ANOVA p-value = 0.034) B. BAL Anti –Hsp27 C. Serum Anti-Hsp70 D.BAL Anti-Hsp70.