Association of alpha-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis.
OBJECTIVE
Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with alpha-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity.


METHODS
One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-alpha-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity.


RESULTS
Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-alpha-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-alpha-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-alpha-actinin antibodies (P < 0.01). In patients with GN, anti-alpha-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with alpha-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA.


CONCLUSIONS
The alpha-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.
Renaudineau
Yves
Y
Brest University Medical School, Brest, France.
Croquefer
Sabine
S
Jousse
Sandrine
S
Renaudineau
Eric
E
Devauchelle
Valérie
V
Guéguen
Paul
P
Hanrotel
Catherine
C
Gilburd
Boris
B
Saraux
Alain
A
Shoenfeld
Yehuda
Y
Putterman
Chaim
C
Youinou
Pierre
P
D000199:Actins / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D015153:Blotting, Western; D004247:DNA / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008181:Lupus Nephritis / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
D000199:Actins; D000974:Antibodies, Antinuclear; D004247:DNA