Patients with Chronic Sarcoidosis have Reduced CD27+IgM+IgD+ Unswitched Memory B cells and an Expanded Population of Terminal Effector CD8+CD27-CD28- T cells

Granulomas that occur in sarcoidosis are histologically identical to those found in a subset of Common Variable Immunodeficiency (CVID) patients where they are associated with a reduction in class switched memory B lymphocytes. The aim of this study was to investigate whether the abnormalities in peripheral blood lymphocyte populations associated with granulomatous variant CVID (gvCVID) are also present in individuals with sarcoidosis. We examined B lymphocyte populations using flow cytometry and found that the reduction of class switched memory (CSM: CD19+CD27+IgM-IgD-) and unswitched memory (CD19+CD27+IgM+IgD+) B cells in our sarcoidosis cohort was similar to that previously reported in gvCVID patients. The reduction of class switched memory B cells in sarcoidosis patients indicated a possible defect in the T cell repertoire as antibody class switching requires T cell help. We subsequently explored the peripheral blood T cell compartment of our sarcoidosis patients. The results identified a population of terminally differentiated effector CD8+ T cells (CCR7-CD45RA-CD127-CD27-CD28-) that were significantly expanded in the peripheral blood of sarcoidosis patients. Terminally differentiated effector CD8+ T cells have been defined as cytolytic, inflammatory cells with reduced replicative capacity. The discovery of abnormal peripheral blood B and T cells compartments in sarcoidosis may be of value in clinical diagnosis and could be relevant to the pathogenic process. Patients with Chronic Sarcoidosis have Reduced CD27+IgM+IgD+ Unswitched Memory B cells and an Expanded Population of Terminal Effector CD8+CD27-CD28T cells Adrian Heaps1*, Veronica Varney2, Shree Bhaskaran1, Brian Ford1, Angelina Mosley3, Ross Sadler4, Lisa Ayers4, Jane Evans2, Amena Warner1, Grant Hayman1, Amolak Bansal1 and Nazira Sumar1 1Department of Immunology, St Helier Hospital, Epsom and St Helier University Hospitals NHS Trust, Carshalton, Surrey, SM5 1AA, UK 2Department of Medicine, St Helier Hospital, Epsom and St Helier University Hospitals NHS Trust, Carshalton, Surrey, SM5 1AA,UK 3Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK 4Department of Clinical & Laboratory Immunology, Churchill Hospital, Oxford, OX37LJ, UK