Anti-neutrophil autoantibodies in tissue damage in systemic lupus erythematosus (135.31)

• Published in: The Journal of immunology (1950) Vol. 184; no. 1_Supplement; pp. 135 - 135.31
• Main Authors: Yu, Yangsheng, Fan, Run, Zhang, Yan, Yue, Yinshi, Gould, Karen, Thiele, Geoffrey, Klassen, Lynell, Fassina, Giorgio, Kimberly, Robert, Zhang, Zhixin, Su, Kaihong
• Format: Journal Article
• Language: English
• Published: 01.04.2010
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.135.31

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which abnormal immune responses attack multiple organs, leading to life-threatening complications. Although the pathogenic role of autoantibodies in SLE has been well established, the most disease-relevant reactivity of autoantibodies and their use as disease progression biomarkers are not fully understood. Using a single-cell PCR approach, we generated a large panel of recombinant antibodies from B cells of SLE patients. We found that a high frequency of SLE-derived antibodies (~ 20%) bind to and activate neutrophils as assayed by degranulation, oxidative burst, calcium influx, and tyrosine phosphorylation. One of the antibodies, S4Ab4, also induces neutrophil extracellular trap (NET) formation and increases cell death to human vein endothelial cells. Using mass spectrometry, we found that S4Ab4 reacts with two neutrophil proteins: lactoferrin and nucleotide-binding oligomerization domains 27 (NOD27). While lactoferrin is a known neutrophil autoantigen, NOD27, a family member of NOD-like pattern recognition receptors, might be a novel autoantigen in SLE. Furthermore, S4Ab4 antibody can cause proteinuria and kidney and lung manifestations when administered into NZB/W F1 lupus-prone mice. Our results show that SLE-derived autoantibodies can directly bind to and activate neutrophils. These anti-neutrophil autoantibodies may play important roles in the disease progression and tissue damage in SLE.