Lymphopenia and high Ki-67 expression in peripheral blood CD4+ and CD8+ T cells associate with progressive sarcoidosis

Abstract

BackgroundEarly identification of patients at risk for progressive sarcoidosis may improve intervention. High bronchoalveolar lavage fluid (BALF) lymphocytes and peripheral blood (PB) lymphopenia are associated with worse prognosis. The mechanisms behind are not disentangled, and to date, it is not possible to predict disease course with certainty.ObjectivesInsight into the frequency of T regulatory cells (Tregs), proliferating CD4+ and CD8+ T cells in BALF and PB in clinically well-characterised patients, may provide clues to mechanisms behind differences in disease course.MethodsNineteen treatment-naïve patients with newly diagnosed sarcoidosis were assessed with BAL and PB samples at diagnosis. From the majority, repeated PB samples were collected over a year after diagnosis. The patients were followed for a median of 3 years and clinical parameters were used to classify patients into resolving, chronic progressive and chronic stable disease. Lymphocyte counts, frequency of Tregsdefined as forkhead box protein 3+ (FoxP3+) CD4+T cells, and proliferating CD4+ and CD8+ T cells assessed with Ki-67 were analysed.ResultsEleven patients disclosed a chronic stable, and eight a progressive disease course, no one resolved during the study period. In PB, lower number of lymphocytes associated with chronic progressive disease, an increased frequency of Ki-67+CD4+ and CD8+ T cells, and a tendency towards higher percentage of FoxP3+CD4+ T cells compared with chronic stable patients.ConclusionA reduction of PB lymphocytes despite increased proliferation of CD4+and CD8+ T cells was observed in patients with chronic active compared with chronic stable sarcoidosis, indicating an increased PB lymphocyte turn-over in patients with deteriorating disease. Measurement of PB Tregs, Ki-67+CD4+ and Ki-67+CD8+ T cells may help in predicting sarcoidosis disease course.