Elevated levels of human beta-defensin 2 and human neutrophil peptides in systemic lupus erythematosus.
OBJECTIVE
Defensins are immunomodulatory peptides and components of the innate immune response. They have been shown to be modulated in various disease states and in response to inflammatory stimuli. Recently, alpha-defensins have been implicated in the pathogenesis of autoimmune diseases. In order to explore whether these defensins may have a role in the pathogenesis of systemic lupus erythematosus (SLE), we sought to determine whether altered expression can be found in SLE patients.


METHODS
Serum and EDTA-blood of 50 SLE patients who fulfilled the American College of Rheumatology (ACR) criteria (aged 41.4 ± 13.3 years) and 28 age- and sex-matched healthy controls were collected. Real-time polymerase chain reaction with gene-specific primers for human neutrophil peptides (HNPs), human beta-defensin 2 and 3 (hBD2, 3) in isolated polymorphonuclear cells and enzyme-linked immunosorbent assay (ELISA) in serum samples were performed. Results of SLE patients were compared with the control group and correlated to routine laboratory parameters, clinical data and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).


RESULTS
SLE patients were predominantly female (90%) with a mean SLEDAI of 5.7 ± 6.1. In sera, patients displayed higher amounts of hBD2 and HNPs when compared with healthy controls. Furthermore, hBD2 correlated with levels of anti-dsDNA antibodies, erythrocyte count and the SLEDAI. Elevated values were observed in patients with myositis (n = 4). Serum HNPs on the other hand correlated with the neutrophil count and was elevated in patients with a rash (n = 7). Lupus patients suffering from transverse myelitis (n = 3) had raised serum-values of both HNPs and hBD2. While no mRNA of hBD2 or hBD3 was detected in polymorphonuclear cells, HNP mRNA was found in both healthy controls and patients without significant difference. Lupus nephritis and rash were associated with higher amounts of HNP mRNA, and the relative amount of copies correlated positively with the SLEDAI and negatively with C3 measurements.


CONCLUSIONS
Serum levels of hBD2 and HNPs are elevated in SLE. The correlations of hBD2 and HNPs to established disease activity parameters and distinct clinical situations suggest that innate immune mechanisms are activated. Defensins may be involved in SLE pathogenesis.
Vordenbäumen
S
S
Department of Endocrinology, Diabetology, and Rheumatology, Heinrich Heine University Düsseldorf, Germany. stefan.vordenbaeumen@med.uni-duesseldorf.de
Fischer-Betz
R
R
Timm
D
D
Sander
O
O
Chehab
G
G
Richter
J
J
Bleck
E
E
Schneider
M
M
D000328:Adult; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D008181:Lupus Nephritis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000209:etiology / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D023084:alpha-Defensins / Q000097:blood* / Q000235:genetics; D023083:beta-Defensins / Q000097:blood* / Q000235:genetics
C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D012333:RNA, Messenger; D023084:alpha-Defensins; D023083:beta-Defensins