Background/Purpose:

The type I interferon (IFN) system is important in the pathogenesis of systemic lupus erythematosus (SLE). We have previously shown an inhibitory effect of IFN-α on interleukin (IL)-6/IL-1 mediated hepatocyte production of C-reactive protein (CRP) in vitro as well as in vivo, partly explaining the poor correlation between disease activity and circulating CRP in SLE. The non-hepatic long pentraxin 3 (PTX3) belongs to the same protein family, and shares some key properties with CRP regarding the handling of cellular debris. This study aimed to evaluate PTX3 as a potential biomarker in SLE, as well as to assess its possible interference with IFN-α by targeting levels in patients and in mechanistic studies on isolated leukocytes.

Methods:

Sera from 243 SLE patients meeting the 1982 ACR and/or the 2012 SLICC classification criteria, and 100 healthy controls were analysed for PTX3 (ELISA) and IFN-α (dissociation-enhanced lanthanide fluoroimmunassay). Disease activity (SLEDAI-2K) varied considerably among the SLE patients at the time point of blood sampling. The majority had established SLE, whereas 9% had recent onset disease.

Neutrophils and peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation of heparinised blood from healthy donors. Leukocyte PTX3 production was stimulated by IL-1β, tumour necrosis factor (TNF), lipopolysaccharide (LPS), and IFN-α. Cell supernatants were analysed for PTX3 by ELISA.

Results:

PTX3 levels were significantly lower in SLE patients (median 2.5 ng/ml) compared to healthy controls (median 4.5 ng/ml); (p <0.0001). PTX3 levels were not correlated with SLEDAI-2K, but with leukocyte-associated variables. Cross-sectional analysis revealed a slight negative correlation between PTX3 and IFN-α (r=-0.154, p=0.017). Patients with no detectable IFN-α (<1 U/ml) had however significantly higher levels of PTX3 (median 2.7 ng/ml) compared to patients with IFN-α >1 U/ml (median 2.1 ng/ml; p=0.01).

In vitro experiments showed IFN-α dependent inhibition of stimulated PTX3 production in healthy blood donor PMBC. No such effect was observed in neutrophils. 

Conclusion:

Average PTX3 levels are lower in SLE patients compared to controls. IFN-α partly inhibits leukocyte PTX3 production in vitro, and its inverse correlation with PTX3 in SLE implies that IFN-α mediated suppression of PTX3 synthesis also occurs in vivo. Since pentraxins have a suggested protective role in SLE, these findings are of interest regarding the handling of apoptotic material and the pathogenesis of SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-alpha-mediated-lowering-of-pentraxin-3-levels-in-systemic-lupus-erythematosus/