Serum autoantibodies in pristane induced lupus are regulated by neutrophil gelatinase associated lipocalin

Abstract

The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity.

Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis

“…Interestingly, LCN2, the most upregulated protein in whole saliva from patients with pSS, is an iron-binding protein involved in the innate immune system, and is particularly responsible for the activation of neutrophils [50]. This suggests the involvement of viral infection in SS pathogenesis.…”

“…Hence, the most upregulated protein in whole saliva from patients with pSS identified in our current analysis (Table 3), is also a key player in tear fluid from these same individuals. Being an iron-binding protein involved in the innate immune system and the activation of neutrophils [50], LCN2 could be viewed as a possible biomarker for SS, whereby screening for LCN2 in whole saliva and tear fluid from patients with pSS could provide additional diagnostic accuracy. This observation further strengthens the notion of a role for viral infection in the pathogenesis of SS.…”

Vaspin, neutrophil gelatinase-associated lipocalin and apolipoprotein levels in patients with psoriatic arthritis

“…Vaspin and NGAL levels were determined to be higher in PsA patients compared with the healthy control group. Vaspin plays a role in atherosclerosis, impaired insulin resistance, obesity and chronic infl ammation (31,32). Vaspin is known to have anti-infl ammatory properties (33)(34)(35).…”

Biomarkers for Kidney Involvement in Pediatric Lupus

“…NGAL-defficient mice were more susceptible to pristane-induced autoimmunity by developing a higher number of antibody-producing cells and higher levels of inflammatory markers in the spleen than their NGAL-sufficient counterparts. Surprisingly, they displayed a milder form of LN, revealing a tissue-specific role [139]. …”