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Abstract: SA-PO930

Discovery and Validation of Novel Circulating Auto-Antibodies in Lupus Nephritis Using Peptide Array Technology

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Prunotto, Marco, Roche Diagnostics International AG, Rotkreuz, Zug, Switzerland
  • Bruschi, Maurizio, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Verrina, Enrico E., Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Angeletti, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Ghiggeri, Gian Marco, Istituto Giannina Gaslini, Genova, Liguria, Italy
Background

Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN) are prototypes of autoimmunity. Autoantibodies determining the first hit in LN have been identified; autoantibodies involved in renal progression remain an open issue.

Methods

We investigated sera of SLE, LN, rheumatologic and normal controls (20/20/60/40) using a high-density peptide array (17,402 peptides) covering the coding sequences of 464 proteins involved in rheumatologic/immunologic processes. The immune-fluorescence intensity was calculated by repeating incubation of sera with peptides 20 times to reduce variability for an overall of 348,040 peptide spots. The noise cutoff was set at IF>50. Validation of results was done by either specific assays (ELISAs) in many more patients (130 SLE, 91 LN) and by renal immuno-histochemistry (12 LN).

Results

Overall, 133 proteins reactive with SLE and LN sera were identified by the peptide array. Annexin A1 (ANXA1) and Formin-like 1 Protein (FMNL1) had the highest probability to be true antigens. Anti-ANXA1 antibodies have been already associated with LN and SLE, FMNL1 is a new identified antigen. Anti-ANXA1 and anti-FMNL1 IgG2 (ELISAs) were high in serum of LN and SLE patients (LN >SLE); FMNL1 co-stained with macrophage markers (CD68) in glomeruli, high expression being associated with proliferative LN (stage IV). FMNL1 was recognized in macrophage cell lysates 'in vitro' by sera of LN patients with high anti-FMNL1 IgG2.

Conclusion

Overall, these findings show many potential antigens in SLE and LN based on an innovative peptide array technology. Circulating anti-ANXA1 and anti-FMNL1 IgG2 were high in both conditions. Anti-FMNL1 antibodies target a protein of macrophages associated with proliferative LN, suggesting that targeting cells potentially involved in tissue damage and/or repair might have a definite role in determining the disease outcome.

Funding

  • Government Support – Non-U.S.