Our previous research has demonstrated that HLA-DPB1*0301 is a very important gene marker for ASA-intolerant asthma (10)

Our previous research has demonstrated that HLA-DPB1*0301 is a very important gene marker for ASA-intolerant asthma (10). Group PK68 I, in comparison with Group III (worth 0.05 was regarded as significant statistically. The statistical analyses had been performed using the SPSS 11.0 for Home windows software program (SPSS Inc., Chicago, IL, U.S.A.) Outcomes Clinical features from the scholarly research topics In Group I, 34 (45.3%) topics had atopic tendencies and 53 (67.6%) had chronic rhinosinusitis. The mean baseline FEV1 worth was considerably lower for Group I than for Group II (beliefs are dependant on chi-square or Fisher’s specific test with modification for multiple evaluations. NS, not really significant. Desk 3 Prevalences of various other autoantibodies predicated on the outcomes for particular IgG to CK18 and CK19 in patients with bronchial asthma Open in a separate window CK, cytokeratin; TGase, tissue transglutaminase; CIC, C1q-binding immune complex; NS, not significant. *meanstandard error mean. DISCUSSION In this study, we have demonstrated that serum anti-CK8, anti-CK18, and anti-CK19 autoantibodies are present in certain populations of bronchial asthma patients. The prevalences of anti-CK18 and anti-CK19 autoantibodies were significantly higher in patients with ASA-intolerant asthma than in healthy controls. PK68 While some of the ASA-tolerant asthmatics had anti-CK18 and anti-CK19 antibodies, the prevalences did not differ from those of normal controls. Furthermore, a proportion of the asthma patients, regardless of ASA sensitivity, had laboratory markers of autoimmunity, including ANA, CIC, and IgG antibody to TGase, although the prevalences of these markers were too low to be statistically significant. The mechanism of induction of autoantibodies in asthma remains unknown. Disruption of bronchial epithelial cells and subsequent exposure of autoantigens or ineffective antigen elimination during the inflammatory process may cause chronic immune stimulation and autoantibody production. In asthma, the bronchial epithelium is characteristically damaged, with shedding of the columnar cells into the airway lumen. Recently, it has been demonstrated that high doses of acetaminophen reduce the levels of glutathione in lung tissues (13), and that the asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis (14). During this early apoptosis, activated caspases cleave a variety of structural proteins. Therefore, it may be postulated that disruption of the cytoskeleton leads to the loss of apoptotic cells from the epithelium and that the altered epithelium becomes an important source of autacoid mediators, chemokines, and growth factors, which contribute to ongoing inflammation (15,16). Cytokeratin is a cytoskeletal structure that is expressed only in epithelial cells. Pairs of keratins seem to be consistently co-expressed in different types of epithelial cells. Thus, CK8, CK18, and CK19, which were used in this study, have been found only in simple epithelia, including both bronchial and lung alveolar epithelial cells (17), which are the major target tissues of asthma. Previously, CK18 has been identified as a bronchial epithelial autoantigen that is associated with non-allergic asthma (12). In isocyanate-induced asthma, CK18 has been identified as a major diisocyanate-binding protein (18), and significantly higher levels of serum IgG to CK19 have been detected (19). CK8 and CK18 contain the caspase cleavage site and have been reported to undergo marked re-organization during apoptosis (16). These findings raise the possibility that fragments of CKs and intracytoplasmic materials are released to the blood vessels and may play a role in the formation of circulating autoantibodies, including ANA and IgG to CKs and TGase. Recent in vitro studies have indicated that the opsonization of extracellular keratin aggregates by IgG-anti-CK autoantibodies plays an important role in promoting the phagocytosis of cytokeratin aggregates (21). This may relate to our results, which show that asthma patients with anti-CK18 and anti-CK19 antibodies have higher prevalences of CIC as well as more severe airway hyperresponsiveness to methacholine. These results suggest that persistent airway inflammation in some patients with PK68 bronchial asthma results from a non-IgE-mediated reaction to endogenous or exogenous antigen, possibly an autoantigen, or to a chronic viral infection (22). These possibilities are PK68 supported by a number of studies, which have shown that some patients with ASA-intolerant asthma have elevated markers of autoimmunity with rheumatic symptoms. Enhanced IgG4 synthesis in association with viral infection and a positive association with the HLA gene marker have been noted (10,11). Our previous study has demonstrated that HLA-DPB1*0301 is a valuable gene marker for ASA-intolerant asthma (10). However, in the present study, no direct relationship was found between this HLA gene marker and the prevalences of IgG antibodies to the three CKs, ANA, IgG antibody to TGase, and CIC. Moreover, none of subjects with these autoantibodies complained of rheumatic symptoms. Tissue transglutaminase (TGase I) is a member of the Ca2+-dependent enzymes that catalyze the cross-linking of proteins. TGase I is expressed in tissues that contain simple epithelia, such as bronchial epithelia, skin epidermis, liver, gastrointestinal tract, kidney, and endothelial cells (23). The induction and Rabbit Polyclonal to GSK3alpha activation of TGase is part of the apoptotic cascade.