Background/Purpose:

The Type I Interferon (IFN) receptor is a heterodimer of chain 1 (IFNAR1) which is required for signaling, and chain 2 (IFNAR2) which binds tightly to IFN.  Soluble forms of IFNAR2 can be produced by proteolytic cleavage or production of an alternatively spliced transcript.  Soluble IFNAR2 can be found in serum and urine however its role and regulation are poorly understood.  Studies have suggested that sIFNAR2 may be elevated in multiple sclerosis (MS) patients, advanced cancer patients and hepatitis C infected patients.  We have examined the sIFNAR2 in healthy donors and a small set of autoimmune patients, to determine its suitability as a member of a biomarker panel for autoimmune diseases.

Methods: Healthy donor and autoimmune Sera and plasma were commercially sourced.  sIFNAR2 and IFN-Beta were determined by single analyte ELISA.  IP-10 and inflammatory cytokines were determined by multiplex ELISA.  IFN activity was determined by a reporter gene assay.  30 male and 30 female normal donor, 59 MS, 67 Systemic Lupus, 16 Rheumatoid Arthritis (RA), 11 Sjogren’s and 10 Scleroderma samples were examined.  Significance of observed differences was determined by 2-tail t-test using Welsh’s correction. 

Results:

The average sIFNAR2 levels are 2.6±0.7 ng/ml with no difference observed between male (n=30) and female healthy donors (n=30).  MS patients on IFN therapy (n=29) had significantly (p=0.0002) higher levels of sIFNAR2 than healthy donors.  Those on other therapies (n=24) were not different from the healthy population but were significantly different than the MS patients on IFN therapy (p=0.0001).  IFN-Beta mass was measurable in 86% of those patients treated with IFN.  IP-10 levels in these patients correlated with IFN dose (r=0.747) while sIFNAR2 did not.  sIFNAR2 levels showed no correlation with treatments such as vitamin-D, copaxone or natalizumab.  Systemic Lupus patients (n=67) had elevated sIFNAR2 (p=<0.0001).  Rheumatoid arthritis (n=16), Sjogren’s (n=11) and Scleroderma patients were not significantly different from normal.  

Conclusion:

Only subsets of autoimmune patients show elevated sIFNAR2 levels.  Although evidence of Type I IFN activation has been observed in RA, Sjogren’s and Scleroderma patients the intensity is thought to be less than that observed for MS patients on IFN-therapy  and Systemic Lupus.  These data are consistent with a model where long term IFN signaling above a certain threshold leads to elevated sIFNAR2.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/soluble-type-i-interferon-receptor-2-is-elevated-by-interferon-treatment-and-in-certain-autoimmune-diseases/