Anti-dsDNA production coincides with concurrent B and T cell activation during development of active disease in systemic lupus erythematosus (SLE).
The objective was to serially analyse T and B cell activation in relation to autoantibody production during the development of relapses in SLE. In a prospective study we serially analysed, by flow cytometry, T cell activation in relation to B cell activation and anti-dsDNA production in quiescent SLE and during the development of a clinical relapse. In addition, we related changes in T and B cell activation to changes in levels of anti-dsDNA and total IgG. During periods with clinically quiescent disease, the expression of activation markers on T cells (IL-2R and HLA-DR) and B cells (CD38) was persistently higher in SLE than in healthy controls (P < 0.001). Percentages of CD20+ CD38+ B cells were related to levels of total IgG (P < 0.02), but not to levels of anti-dsDNA. Development of disease activity was paralleled by an increase in the percentages of CD4+ T cells (P < 0.005) and CD20+ CD38+ B cells (P < 0.001), which were interrelated. Increases in B cell activation were related to increases in levels of anti-dsDNA (P < 0.005), but not to changes in total IgG levels. B cells expressing high levels of CD38 spontaneously produced IgG class anti-dsDNA in vitro. Persistence of activated B cells during periods with clinically quiescent disease in SLE seems to underly hypergammaglobulinaemia but not anti-dsDNA production. Prior to clinical disease activity, further activation of T and B cells occurs, which is paralleled by rises of anti-dsDNA but not of total IgG. This suggests that the production of anti-dsDNA is a T cell-dependent antigen-driven process, which is independent of the polyclonal activation of the immune system inherent to the disease.
Spronk
P E
PE
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Horst
G
G
Van Der Gun
B T
BT
Limburg
P C
PC
Kallenberg
C G
CG
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000974:Antibodies, Antinuclear / Q000032:analysis*; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007376:Interleukin-2 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000276:immunology; D011446:Prospective Studies; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology*
D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D018951:Antigens, CD20; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D007074:Immunoglobulin G; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1