High serum allograft inflammatory factor 1 is associated with poor response to TNFα inhibitors in ankylosing spondylitis patients

다국어 초록 (Multilingual Abstract)

Background: Anti-TNFα therapy has been proven to be highly efficacious in ankylosing spondylitis (AS). Considering its high costs and potential risk for adverse events, early detection of non-responders to anti-TNFα agents is critical.
Objectives: To identify serum markers predicting clinical response to TNFα blockers in AS
Methods: Baseline gene expression differences were screened by pathway focused gene assays of peripheral blood RNA from 6 AS patients (3 responders and 3 non-responders) before initiating anti-TNFα treatment, and selected results were confirmed by qRT-PCR in 18 patients (11 responders and 7 non-responders). Concentration of corresponding serum protein was measured by ELISA and compared in 69 responders and 48 non-responders. No response to TNFα blocker was
defined as less than 50% improvement in Bath ankylosing spondylitis disease activity score (BASDAI) at week 14 from baseline.
Results: Nine candidate genes were selected from gene assays and validated by qRT-PCR. Among these genes, the expression of allograft inflammatory factor 1 (AIF1) was 3.52 fold higher in non-responders than responders (p=0.032). The serum AIF1 level at baseline was significantly higher in BASDAI 50 non-responders; median 32.8 [IQR 20.6;67.3] pg/ml in responders and 54.2 [28.9;91.0] pg/ml in nonresponders
(p=0.033). AIF1 level of 63.5 pg/ml or more was associated
with higher risk for BASDAI > 5.0 at week 14 after anti-TNFα treatment (adjusted OR 6.953, p=0.002).
Conclusion: Baseline serum AIF1 level was higher in TNFα blocker non-responders. After adjusting age and initial BASDAI, high concentration of baseline AIF1 was associated with high disease activity after TNFα blocker treatment. These results suggest that AIF1 may be a novel serum marker for predicting non-responders to anti-TNFα therapy in AS.

목차 (Table of Contents)

• I. Introduction 1
• II. Subjects and Methods 4
• III. Results 11
• IV. Discussion 30
• V. References 35