Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
KeyIntel Medical Inc., Toronto, Ontario, Canada.
Arthritis Res Ther. 2022 Jul 8;24(1):164. doi: 10.1186/s13075-022-02854-2.
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.
男性 HLA-B27 阳性的放射学轴性脊柱关节炎（r-axSpA）患者易发生严重的脊柱放射学进展，但潜在机制尚不清楚。我们最近发现，持续升高的载脂蛋白 2（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都检测到 L 和 LCN2-MMP9（LM）的同时升高。我们想知道 L 和 LM 在 r-axSpA 发病机制中是否发挥类似作用。
我们分析了 190 名 axSpA 患者（123 名放射学和 67 名非放射学 axSpA），他们没有检测到可检测的循环 Oncostatin M，以避免由于途径之间的串扰而引起的并发症。从每位患者的单个血样中测量 L 和 LM 水平，并与 MRI 和改良 stoke AS（mSASS）评分相关联。评估升高的 L（L+）或同时升高的 L 和升高的 LM（LM+）模式与 B27 状态和性别之间的关联。
在 L+LM+ axSpA 患者中，L 和 LM 水平均与 MRI SPARCC SIJ 评分相关，但只有 LM 水平与 MRI Berlin 脊柱评分相关，提示 LM 是 SIJ 和脊柱炎症的生物标志物。在最小脊柱强直（mSASSS<10）的患者中，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 与疾病进展有关。在 B27+ L+LM+男性患者中，L 和 LM（而非 CRP）水平与 mSASSS 相关。B27 阳性和男性均对脊柱炎进展具有相加作用，提示同时存在高 L 和 LM 升高与 B27+男性患者的更严重的放射学损害有关。B27 阴性的男性 L+患者或 L+的女性患者更可能患有较轻的疾病。
L 和 LM 是 r-axSpA 患者的 SIJ 和脊柱炎症以及强直性发展的信息生物标志物。独特的 L+LM+或 L+模式不仅可以区分临床侵袭性和较轻的疾病过程，而且还可以解释为什么 B27 阳性的男性患者最容易发生严重的强直。
