Background IL-31 is a newly-described cytokine mainly produced by activated Th2 cells. IL-31 acts through IL31-RA and oncostatin heterodimeric receptors that activate STAT3 and STAT5. So far, IL31 has been mainly involved in airway hypersensitivity and atopic dermatitis. More recent data suggest its involvement in psoriasis, inflammatory bowel disease and osteoporosis.
Objectives We aimed to assess IL-31 serum levels in patients with recent onset axial spondyloarthritis (SpA) from DESIR cohort.
Methods The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early inflammatory back pain (IBP) (duration >3 months and <3 years) suggestive of AxSpA (mean age 33.8 years; 53.8% women, 57% fulfilled the ASAS criteria). IL-31 and sCD40L were assessed using the multiplex and high sensitive 17-Plex ELISA (Bio-Plex Pro Human Cytokine 17-Plex Immunoassay, BioRad). Serum levels were assessed at baseline in 3 subgroups of patients: i. patients from the DESIR cohort fulfilling the ASAS criteria (ASAS+ group, n=443); ii. IBP patients from the DESIR cohort not fulfilling the ASAS criteria (ASAS− group, n=265); iii. Healthy controls age and sex-matched to a random sample of the DESIR cohort patients (control group, n=79).
Results IL31 was significantly increased (p<0,001) in the ASAS+ group (median=7.7 pg/ml ± 15.4, mean 12.6 pg/ml) and ASAS− group (6.3 pg/ml ± 16, mean=11.3 pg/ml) compared to the control group (median=0.0±3.1, mean=1.1 pg/ml). IL31 was correlated with sCD40L (r=0.62; p<0.0001), and with DKK-1 (r=0.27; p<0,001). Patients exhibiting a high level of IL31 had a mSASSS score <1 (Yes 7.7 ± 10.7 versus No 13.02 ± 15.07; p=0.005). The multivariate analysis in ASAS+ group showed an association between IL-31 and sCD40L (p<0.0001), mSASSS≥1 (p=0.007), DKK-1 (p=0.002) and low bone density defined by Z-score < -2 (p=0.04). In the multivariate logistic analysis, IL-31 was independently associated with low bone density (p=0.02) in a model also including age (ns), gender (p=0.0008), and CRP (P=0.0003).When assessing patients with osteoporosis (T score <2.5), IL-31 was still independently associated (p=0.025) as well as gender (p=0.005). IL-31 was also independently associated with protection from axial structural damages (OR 0.07 [0.96–0.99];p=0.005) as well as other parameters included in the model: age (p<0.0001), and smoking (p=0.04). The same significant association between IL-31 and protection from structural damage when focussing on ASAS+ patients (p=0.007) or on patients fullfilling the Amor criteria (p=0.009). Only a trend was observed for patients fullfilling the ESSG criteria (p=0.07).
Conclusions IL31 serum levels are correlated with sC40L suggesting the role of activated T-cells in IL-31 expression. IL31 is also significantly correlated with the Wnt signaling inhibitory protein DKK-1. Increased levels of IL-31 might protect patients from structural damages but are also associated with low bone density. These preliminary results regarding IL-31 mediated bone effects in DESIR cohort need to be confirmed in more severe forms of the disease.
Disclosure of Interest None declared