Eosinophil Activation in Wegener’s Granulomatosis: A Harbinger of Disease Progression?

Abstract

Abstract: : Purpose:To investigate the relation of the state of eosinophil activation in biopsied tissue of patients with active, limited form of Wegener’s granulomatosis (WG), affecting the eye, and subsequent disease activity. Methods:The retrospective review of the records of a cohort of patients who presented to the Immunology and Uveitis service of the Massachusetts Eye and Ear Infirmary between 1988 and 1996 with corneoscleral manifestations of WG was conducted. Immunohistochemical analysis of biopsied ocular specimens obtained from ten patients with active ocular limited Wegener’s granulomatosis was performed on snap–frozen tissue. The sections were probed with antibodies BMK–13, EG1 and EG2 to assess the presence of major basic protein (MBP) and eosinophil cationic protein (ECP); indicators of eosinophil activation. Antibody binding to eosinophils and extra cellular matrix was assessed by using an alkaline phosphatase /anti–alkaline phosphatase technique. Results:Tissues from 4 of the 10 patients with active WG limited to the eye demonstrated eosinophils which bound BMK–13, EG1, and EG2, indicating the presence of MBP and both the stored and secreted forms of ECP. The WG progressed to the complete form in 2 of these patients who received no or inadequate treatment. The other two, treated with cyclophosphamide for one year, experienced complete resolution of scleritis and did not progress to the complete form of WG during 1–5 years of observation after therapy. The specimens from the remaining 6 patients showed no staining with any of the eosinophil antibodies. None of these patients progressed to generalized WG. Conclusions: These observations suggest that there may be a correlation between the presence of activated eosinophils and the likelihood of progression of WG from its limited to its complete form in patients not treated with Cyclophosphamide. Although there is increasing evidence suggesting the role of eosinophil in the pathosis of WG, to date there is no study examining their association with ANCA and disease activity. We have demonstrated that the presence of activated eosinophils in ocular tissues from the patients with active limited WG may be a harbinger of systemization if the patient is left untreated. In addition to c–ANCA, evidence of eosinophil activation may help identify the high risk patient who should have more aggressive therapy. The presence of activated eosinophils in sclera or conjunctiva of patients with ocular limited WG may predict the progression of this disease to the complete form.

Keywords: autoimmune disease • clinical laboratory testing • immunohistochemistry