Reduced anti-TNFalpha autoantibody levels coincide with flare in systemic lupus erythematosus.
Deviating cytokine patterns, as a consequence of aberrant immunoregulation, is implicated to be of aetiopathogenetic importance in systemic lupus erythematosus (SLE). To evaluate the possibility of anti-cytokine autoantibody-mediated cytokine regulation/dysregulation, IgG class autoantibodies against cytokines (IL-1beta, IL-6, IL-10, TNFalpha and TGFbeta(1)) were analysed by enzyme-linked immunosorbent assay (ELISA) in serial serum samples from clinically well-characterized SLE patients and in normal human sera (NHS). Anti-TNFalpha autoantibody levels were lower in patients with active disease compared to inactive disease (P<0.001) as well as to NHS (P<0.001). The anti-TNFalpha antibody levels correlated inversely to the SLE disease activity index (SLEDAI) (r(2)=0.07, P<0.01), whereas anti-TGFbeta antibodies were raised in SLE and correlated positively to levels of complement factor C1q (r(2)=0.08, P<0.005). Generally raised anti-cytokine antibody levels and correlations to disease activity measures were found in one individual. Inverse correlations were found comparing SLEDAI scores and autoantibodies to TNFalpha (r(2)=0.92) and IL-6 (r(2)=0.86) and positive correlations were found between levels of anti-TNFalpha and C1q (r(2)=0.86) and C3 (r(2)=0.90). We show, for the first time, a coincidence between reduced anti-TNFalpha autoantibody levels and disease exacerbation in SLE, which is of interest regarding aetiopathogenesis and disease control.
Sjöwall
Christopher
C
Division of Rheumatology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. chrsj@imk.liu.se
Ernerudh
Jan
J
Bengtsson
Anders A
AA
Sturfelt
Gunnar
G
Skogh
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D015922:Complement C1q / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015850:Interleukin-6 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D001323:Autoantibodies; D003176:Complement C3; D016207:Cytokines; D007074:Immunoglobulin G; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015922:Complement C1q