Immunoadsorption of Immunoglobulins Alters Intracytoplasmic Type 1 and Type 2 T Cell Cytokine Production in Patients with Refractory Autoimmune Diseases

Abstract

Intracellular cytokine staining and flow cytometry were used to investigate whether immunoadsorption (IA) of immunoglobulins alters intracytoplasmic cytokine production in CD4+ and CD8+ T cells from the blood of patients with refractory rheumatoid arthritis (n = 7), membrane proliferative glomerulonephritis (n = 1), and Goodpasture's syndrome (n = 1). Four patients (Group 1) showed severely depressed production of TNF-alpha, IL-2, IFN-gamma, and IL-4 by CD4+ and CD8+ T cells and responded to 3 IA sessions with significant increases in CD4+TNF-alpha+, CD4+IL-2+, and CD8+IL-2+ T cells. Also, a tendency toward increased percentage levels of CD4+ T cells producing IFN-gamma or IL-4 and of CD8+ T cells producing either TNF-alpha or IFN-gamma was seen, but due to the small number of patients investigated, these differences did not attain statistic significance. Group 2 (n = 5) showed unimpaired intracellular cytokine levels and responded to IA with a heterogeneous pattern of changes in TNF-alpha, IL-2, IFN-gamma, and IL-4 production, but these alterations were smaller than those in Group 1. The present findings indicate that the extracorporeal removal of immunoglobulins by anti-IgG or protein A adsorber columns has an impact on T cell immunity and suggest that modulating effects on cellular immune system function are involved in the mode of action of IA.