T and B cell immune response to a 55-kDa endothelial cell-derived antigen in severe asthma

Current concepts on the pathogenesis of chronic asthma emphasize the role of several inflammatory cell populations and their respective mediators that interact in a complex network. However, beside inflammatory cells, lymphocytes are also present in asthmatic airways. Although little is known about their involvement in asthma, it has been suggested that lymphocytes may participate in the development of chronic inflammation either through lymphokine secretion or through antibody production. In this study, we describe circulating IgG autoantibodies, directed against a common 55-kDa antigen shared by platelets and cultured endothelial cells, and found in 34 out of 97 asthmatic patients. Among epidemiological, clinical and biological characteristics of these asthmatic patients, the anti-55-kDa antigen antibodies are mainly restricted to patients with negative cutaneous prick tests (p = 0.0014), and corticosteroid-dependent asthma (p = 0.0036). These antibodies were also detected in a few patients with autoimmune disorders like systemic lupus erythematosus (3/30) or rheumatoid arthritis (2/36). Both platelet and endothelial cell antigens were cross-reactive, had an isoelectric point between 8.0 and 9.0, were insensitive to reducing agents such as 2-mercaptoethanol, and were not present on either platelet or endothelial cell surface, as determined by immunostaining assay. [3H]Thymidine incorporation assay with peripheral blood mononuclear cells from patients in the presence or in the absence of 55-kDa antigen, purified from nitrocellulose sheets demonstrated a specific incorporation in 6 out of 13 patients with circulating anti-55-kDa antigen antibodies, with index values ranging from 12 to 3. Such a T cell reactivity has also been observed in 3 out to 17 patients without detectable serum anti-55-kDa antigen antibodies. Moreover, a significant correlation was found between index values of antigen-specific T cell reactivity and the forced expiratory volume in one second (r = 0.544, p = 0.003). Our data indicate that the detection of such antibodies allows to distinguish a subgroup of asthmatics in terms of severity and to suggest a relationship between clinical severity and T and B cell autoreactivity to the 55-kDa platelet/endothelial cell antigen.