| Objectives: Ankylosing spondylitis(AS)is a kind of progressive arthritis caused by long-term chronic inflammatory stimuli in the joints of the spine.Recent studies have shown that interferon lambda(IFN-?)is involved in the development of many rheumatic diseases,but the relationship between serum IFN-? expression levels and disease activity in AS patients has not been reported.This study aims to determine the changes of serum levels of IFN-? subtypes(interleukin-29(IL-29),interleukin-28A(IL-28A),interleukin-28B(IL-28B))in the AS patients treated with tumor necrosis factor-? inhibitors(TNFi)and analyze the correlations between serum IFN-? levels and disease activity.This study also investigated the role of serum IFN-? subtypes in the pathogenesis of AS,and find out whether the IFN-? subtypes can be used as a biomarker for the baseline predictors of TNFi treatment response in AS.Patients and Methods: The study included 57 AS patients(6 females,51males),who had been diagnosed with AS and had active disease before the start of the study.The healthy control(HC)group included 50 healthy,age-and sex-matched individuals.These patients received a kind of TNFi treatment(the TNF-? fusion protein,etanercept)as for 25 mg twice weekly together with one of non-steroidal anti-inflammatory drugs (NSAIDs)including celecoxib,diclofenac,and etoricoxib.These patients were followed up for 6 months.The pre-treatment and post-treatment clinical parameters(including C-Reactive protein(CRP),erythrocyte sedimentation rate(ESR),Bath AS disease activity index(BASDAI),Bath AS measurement index(BASMI),Bath AS function index(BASFI),AS disease activity score using CRP(ASDAS-CRP),Assessments in Ankylosing Spondylitis(ASAS)20 response criteria(ASAS20))were collected.The differences and associations of these clinical parameters were evaluated and compared.The enzyme-linked immunosorbent assay(ELISA)was used to evaluate the serum levels of IL-29,IL-28 A and IL-28 B in patients with AS before,at 1,3,and 6 months after treatment.Results:(1)Serum IL-28 A levels were significantly higher in AS patients than in HC(p=0.003);serum IL-28 B levels were significantly lower than HC(p=0.000);serum IL-29 levels were not statistically different from those of HC(p>0.05).(2)Monitoring the change trend of serum IFN-? subtype at different time points in AS patients,the results showed that serum IL-28 A levels at 1,3,and 6 months after TNFi treatment in AS patients were significantly higher than those of HC(p <0.01);the serum levels of IL-28 B were significantly lower than those of HC(p < 0.01).The serum levels of IL-28 A increased significantly at 1 month after treatment,but decreased and gradually approached HC expression levels at 3 months after treatment.During the 6months,it was consistently significantly higher than the baseline level(p<0.01),and serum IL-28 B expression levels continued to increase and gradually approached the HC expression level after treatment.Serum levels of IL-29 at 1 month and 3 months after TNFi treatment were significantly higher than those at baseline(p=0.002).But serum levels of IL-29 in the AS patients were significantly higher than those in HC only at 3 months after treatment.(p=0.041).(3)Analysis of the difference of IFN-? expression levels between 1,3,6 months after treatment showed that there was no significant difference in serum IL-29,IL-28 A and IL-28 B levels(p> 0.05).The indicators of disease activity(ESR,CRP,BASDAI,ASDAS-CRP)at the 1,3,6 month after treatment showed a significant decrease compared with the baseline disease activity indexes(p<0.01).Serum levels of IL-29,IL-28 A,IL-28 B,ESR,CRP were in a steady-state level 1month after treatment till to the 6month(p<0.05);ASDAS-CRP score continued to decline till 3month after treatment(p<0.05),and then in a steady-state;BASDAI continued to decline during the treatment period(p<0.05).The increased trend of serum IL-28 A,IL-28 B after TNFi treatment in the AS patients was opposite to the decreased trend of disease activity.(4)There was no correlation observed between serum IL-29,IL-28 A,IL-28 B levels and the disease activity measured at baseline of the AS patients(p > 0.05).Serum levels of IL-28 A were negatively correlated with ESR levels at 1 and 6month after treatment(r=-0.266,p=0.046;r=-0.286,p=0.034,respectively);serum levels of IL-28 A were negatively correlated with BASDAI at 3month after treatment(r=-0.269,p=0.043);serum levels of IL-29 were negatively correlated with BASDAI at 3month after treatment(r=-0.299,p=0.024).There was no significant correlation between ?IL-29,?IL-28 A,?IL-28 B levels and ?clinical parameters measured in the AS patients at 1 month after treatment(p > 0.05).(5)There was no significant difference of the serum IL-29,IL-28 A,IL-28 B levels at baseline between the response positive group and the no response group(p > 0.05).Conclusion: This study was the first time to detect the expression levels of serum IFN-? in AS patients.Serum IL-28 A levels in AS patients were significantly higher than those in HC;serum IL-28 B levels were significantly lower than those in HC.;serum IL-29 levels were not statistically different from those of HC.The serum levels of IFN-? in AS patients after TNFi treatment showed a negative correlation with disease activity indicators,which may provide a new target for the treatment of AS.These findings indicated that IFN-? may be involved in the pathogenesis of AS. |
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