Neutrophil Gelatinase Associated Lipocalin (NGAL) deficiency accelerates the onset of serum autoantibodies in pristane induced lupus (60.10)

Abstract

Abstract NGAL (lipocalin-2), a member of the lipocalin superfamily, is expressed by neutrophils, hepatocytes, and renal resident cells following ischemia or inflammatory conditions & is involved in innate immune responses during infection. However, its role in adaptive immunity has not been described. Previously, we had found that NGAL is instrumental in the pathogenesis of antibody mediated nephritis. To investigate a possible role for NGAL in the generation of autoreactive antibody responses, we examined its effect in an experimental lupus model. We injected pristane (0.5 ml per mouse i.p.) into wild type B6 (n=10) and NGAL-deficient (NGAL-/-) (n=10) mice and followed the course of disease. Analyzing the levels of serum autoantibodies at 3 months post injection, NGAL-/- mice had significant increases in IgG2a (p=0.007) and IgG2b (p=0.019) anti-double stranded DNA antibodies, and IgG2a (p=0.002) & IgG2b (p=0.010) anti-single stranded DNA antibodies, and IgG anti-histone antibodies (p=0.025) as compared to pristane challenged, NGAL sufficient mice. Immunoprecipitation studies showed elevated serum anti-Sm/RNP antibodies in NGAL-/- mice compared to the WT mice at 3 months post injection, with an increase in titer and epitope diversity of this response at 6 months post injection. In conclusion, NGAL delays the onset of anti-nuclear antibodies in pristane induced lupus. The mechanisms by which NGAL plays a protective role in humoral autoimmunity are under investigation.