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‐α, IL‐2, IFN‐γ, and IL‐4 by CD4+ and CD8+ T cells and responded to 3 IA sessions with significant increases in CD4+TNF‐α+, CD4+IL‐2+, and CD8+IL‐2+ T cells. Also, a tendency toward increased percentage levels of CD4+ T cells producing IFN‐γ or IL‐4 and of CD8+ T cells producing either TNF‐α or IFN‐γ 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‐α, IL‐2, IFN‐γ, 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.

Prolonged Clinical Remission of Patients with Severe Pemphigus upon Rapid Removal of Desmoglein-Reactive Autoantibodies by Immunoadsorption

“…In patients with systemic lupus erythematosus, the authors saw a transient decrease in the CD4/CD8 ratio, a reduction of antigen-activated T cells and an increase in naïve T lymphocytes after IA [28]. Good evidence for an impact of IA on altering T cell function is provided by another report from Hehmke et al [29]. In a cohort of 9 patients with refractory autoimmune diseases who underwent 3 IA treatments, T cell cytokine profiles were investigated.…”

“…In a cohort of 9 patients with refractory autoimmune diseases who underwent 3 IA treatments, T cell cytokine profiles were investigated. In this study extracorporeal removal of IgG and circulating immune complexes induced distinct alterations in the cytokine patterns of T effector cells [29]. Thus, the effect of IA may not be restricted to the mechanistic removal of autoantibodies but is extended to functional alterations of the T cell compartment.…”

Apheresis of Immune Diseases and Apheresis Using Immunological Specificity

“…In addition, these cell types also are targets for selective cytapheresis. Recent reports indicated that immunoadsorption of immunoglobulins may affect both the Th1/Th2 and Tc1/Tc2 balance in the blood (2,18); however, the possibility of using cytokine engineering, which uses cytokines directly as a target of apheresis rather than the molecules and cells conventionally used, should be considered for the regulation of immune cell interactions and to correct immune imbalances.…”

Background and Indications for Protein A‐Based Extracorporeal Immunoadsorption

“…On the other hand, while the antibody eliminating capacity of Immunosorba seems to underline its mode of action, our investigations suggest that intracytoplasmic Type I and Type II T‐cell cytokine production can be altered upon immunoadsorption with double column systems. Thus to date, an unknown immunomodulatory pathway may also be operative with Immunosorba (55).…”