Characteristics of B cells and autoantibodies in SLE

Abstract

The presented work in this thesis deals with the previously unknown characteristics of global B cell alterations and ANAs in systemic lupus erythematosus (SLE). Firstly, we have shown in the studies described in chapter 2, for the first time, a direct relationship between type 1 IFN and plasmablast (PB) expansion in a subgroup of patients with SLE, which is also linked to hypergammaglobulinemia, the presence of anti-Sm/RNP70 in serum, and increased disease activity. A direct link to the capacity of enhanced B cell differentiation of memory B cells from SLE patients is found in chapter 3, where these B cells exhibit hypersensitivity towards stimulation of their CD40-receptor. Analysis of anti-nuclear antibody (ANA) dynamics described in chapter 4 has shown that levels of anti-dsDNA and anti-Sm display similar dynamics, in contrast to anti-SS-A and anti-SS-B. The heterogeneity of ANA characteristics pertaining to Fc-glycosylation investigated in chapter 5 has shown that anti-dsDNA and anti-SS-A have different glycosylation profiles compared to each other and to total IgG in sera of SLE patients and healthy donors.