Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis. We analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed. In L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease. L and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis.

中文翻译：

---

LCN2 和 LCN2-MMP9 在脊柱炎影像学发展中的作用：性别和 HLA-B27 状态差异

男性 HLA-B27 阳性影像学中轴型脊柱关节炎 (r-axSpA) 患者容易出现严重的脊柱影像学进展，但其潜在机制尚不清楚。我们最近表明，持续升高的 Lipocalin 2 (LCN2; L) 反映了骶髂关节 (SIJ) 炎症。LCN2 与 MMP9 结合。在许多炎症性疾病中检测到 L 和 LCN2-MMP9 (LM) 的伴随升高。我们询问 L 和 LM 在 r-axSpA 发病机制中是否发挥相似的作用。我们分析了 190 名未检测到循环制瘤素 M 的 axSpA 患者（123 名放射影像学和 67 名非放射影像学 axSpA），以避免由于通路之间的串扰引起的并发症。测量了每位患者的单一血液样本的 L 和 LM 水平，并与 MRI 和改良的 stoke AS (mSASS) 评分相关联。评估了升高的 L (L+) 或并发的 L+ 和升高的 LM (LM+) 模式与 B27 状态和性别的关联。在 L+LM+ axSpA 患者中，L 和 LM 水平都与 MRI SPARCC SIJ 评分相关，但只有 LM 水平与 MRI Berlin Spine 评分相关，这表明 LM 是 SIJ 和脊柱炎症的生物标志物。在轻度脊柱强直（mSASSS < 10）患者中，65% 的男性 r-axSpA 患者为 L+LM+，而 30% 和 64% 的女性患者分别为 L+LM+ 和 L+，支持 LM 对疾病的作用进展。在 B27+ L+LM+ 男性患者中，L 和 LM（但不是 CRP）水平与 mSASSS 相关。B27 阳性和男性对脊柱炎进展具有累加效应，表明同时高 L 和 LM 升高与 B27+ 男性患者具有更显着的放射学损伤相关。L+ B27 阴性男性患者或 L+ 女性患者的病情较轻。L 和 LM 是 SIJ 和脊柱炎症以及 r-axSpA 患者强直性发展的信息生物标志物。独特的 L+LM+ 或 L+ 模式不仅可以分别区分临床侵袭性和较轻的病程，还可以解释 B27 阳性男性患者最容易患严重强直。