Combination of anti-C1q and anti-dsDNA antibodies is associated with higher renal disease activity and predicts renal prognosis of patients with lupus nephritis.
BACKGROUND
Although nephritogenic autoantibodies are considered to play a central role in the initiation of lupus nephritis, whether these autoantibodies are associated with renal clinical and pathological activity or renal outcome is still controversial. Here, we investigated the associations of certain serum autoantibodies with renal disease activity and renal outcome in a large cohort of Chinese patients with lupus nephritis.


METHODS
One hundred and thirty-six Chinese patients with biopsy-proven lupus nephritis and with long-term follow up data were studied. Sera at renal biopsy were tested for a panel of autoantibodies, including anti-nuclear antibodies, anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen antibodies, anti-C-reactive protein antibodies, anti-C1q antibodies, anti-cardiolipin antibodies and anti-β2-glycoprotein I antibodies. Associations of these autoantibodies with clinical features, laboratory findings, histopathological data and renal outcomes were further investigated.


RESULTS
Among the various autoantibodies, anti-dsDNA and anti-C1q antibodies were better than other antibodies to evaluate the renal disease activity. Anti-dsDNA antibodies were correlated with higher incidence of leukocyturia (P< 0.05), total pathological activity index (AI) score (P< 0.05), endocapillary hypercellularity (P< 0.05), subendothelial hyaline deposits (P< 0.05) and leukocyte infiltration (P< 0.05). Anti-C1q antibodies were correlated with leukocyturia (P< 0.01), hematuria (P< 0.003) and the majority of the histopathological AIs including total AI score (P< 0.003), endocapillary hypercellularity (P< 0.003), cellular crescents (P< 0.05), karyorrhexis/fibrinoid necrosis (P< 0.003), subendothelial hyaline deposits (P< 0.003) and leukocyte infiltration (P< 0.01). Patients with both anti-dsDNA and anti-C1q antibodies had higher renal disease activity and poorer renal outcome (log-rank test: P= 0.048) compared with those without the two antibodies. In univariate survival analysis of renal prognosis, neither the presence of anti-C1q nor the presence of anti-dsDNA antibodies was a risk factor of renal survival. However, the combination of the two antibodies predicted renal prognosis (hazard ratio 4.40, 95% confidence interval: 1.268-15.269, P= 0.02).


CONCLUSIONS
Anti-C1q antibodies are more closely correlated with renal disease activity than the other autoantibodies. The combination of anti-C1q and anti-dsDNA autoantibodies indicates higher renal disease activity and predicts poor renal outcome.
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, PR China.
Xiao-wei
XW
Yang
Ying
Y
Tan
Feng
F
Yu
Ming-hui
MH
Zhao
D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000974:Antibodies, Antinuclear / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D015922:Complement C1q / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D008181:Lupus Nephritis / Q000150:complications* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D015996:Survival Rate; D055815:Young Adult
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; C033055:anti-extractable nuclear antigen antibodies; D015922:Complement C1q