Anti-CCL18 monoclonal antibody, clone 6H9

Background: Recent research shows that both pediatric and adult patients with eosinophilic esophagitis (EoE) experience esophageal remodeling marked by increased collagen deposition in which TGF-beta plays an important role. However, limited data are available on the intensity and reversibility of fibrous remodeling in adults with EoE. Objective: We sought to analyze differences in collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene expression along with other changes induced by prolonged treatment with fluticasone propionate in adults with EoE. Methods: Ten adults given consecutive diagnoses of EoE were studied prospectively. Deep esophageal biopsy specimens were obtained before and after 1 year of treatment with fluticasone propionate. Collagen deposition in the LP was assessed in tissue sections with the aid of the Masson trichrome technique. IL5, TGFB1, fibroblast growth factor 9 (FGF9), and CCL18 gene expression was quantified through real-time PCR. EoE results were compared among samples from 10 adult patients with gastroesophageal reflux disease and 10 control subjects with healthy esophagi. Results: Patients with EoE showed a significant increase in subepithelial collagen deposition; this correlated positively with eosinophil density in the LP and the patient's age. Prolonged steroid treatment induced a nonsignificant reduction in subepithelial fibrosis, which remained significantly higher than in control subjects. Profibrogenic cytokine gene expression also increased in patients with EoE, with IL5 (P < .001), FGF9 (P = 5.005), and CCL18 (P = .008) all significantly upregulated. After 1 year of treatment, a reduction was observed in gene expression; for CCL18 expression, this decrease was statistically significant (P < .001). Conclusions: Esophageal remodeling is associated with upregulated gene expression of profibrogenic cytokines in adults with EoE. Prolonged treatment with fluticasone propionate leads to a nonsignificant reduction in subepithelial collagen deposition accompanied by downregulation of profibrogenic cytokine gene expression, with that of CCL18 being especially significant. (J Allergy Clin Immunol 2011;128:1037-46.)

Introduction: Hypersensitivity pneumonitis (HP) is an immunologically induced lung disease that develops after inhalation of certain environmental antigens only in subjects with susceptibility to antigens. Therefore, both environmental and host immunological factors play important roles in the aetiology and pathogenesis of HP.Areas covered: Determination of an inciting antigen is crucial for diagnosis, treatment and monitoring. For treatment, modification of the environment and of the host immune response are important. The former includes reduction of antigenic burden (i.e. disinfectant, cleaning), protective devices (i.e. filter, respiratory protection mask, ventilation) and avoidance of inciting antigens. The latter includes corticosteroids, lung transplantation and smoking cessation. For monitoring, measurement of serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D concentrations can be used to screen for HP and to detect HP activity.Expert commentary: Measurement of an inciting antigen may be useful to predict the progression and prognosis of the disease. Treatment and monitoring are challenging in chronic HP with fibrosis.