Brady Makayla P, Chava Saiteja, Tandon Shweta, Rane Madhavi J, Barati Michelle T, Caster Dawn J, Powell David W
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
J Clin Med. 2022 Jun 3;11(11):3199. doi: 10.3390/jcm11113199.
Background: Lupus nephritis (LN) is a prevalent and severe complication of systemic lupus erythematosus (SLE). Non-invasive diagnostics are limited, and current therapies have inadequate response rates. Expression of the chemokine Interferon-γ-induced protein 10 (IP-10) is regulated by Interferon-γ signaling and NF-κB, and its molecular activity and enhanced urine concentrations are implicated in LN, but its utility as a diagnostic marker and association with demographic, clinical, or pathologic features is not defined. Methods: 38 LN patients and 11 patients with non-LN glomerular diseases (GD) with active disease were included. Eighteen of the LN patients had achieved remission at one follow-up during the study time. Serum and urine were obtained from these samples, and the IP-10 levels were measured. Results: Serum and urine IP-10 levels are significantly enhanced in LN patients with active disease as compared with normal individuals (serum average 179.7 pg/mL vs. 7.2 pg/mL, p < 0.0001; urine average 28.7 pg/mg vs. 1.6 pg/mg, p = 0.0019) and patients with other forms of glomerular disease (serum average 179.7 pg/mL vs. 84.9 pg/mL, p = 0.0176; urine average 28.7 pg/mg vs. 0.18 pg/mg, p = 0.0011). Urine IP-10 levels are significantly higher in patients with proliferative LN (PLN) than those with membranous LN (MLN) (average 32.8 pg/mg vs. 7.6 pg/mg, p = 0.0155). Urine IP-10 levels are also higher in MLN versus primary membranous nephropathy (MN) (average 7.6 pg/mg vs. 0.2 pg/mg, p = 0.0193). Importantly, serum IP-10 levels remain elevated during active LN and LN remission, but urine IP-10 levels are decreased from active LN to remission in 72% of our patients. Lastly, serum, but not urine IP-10 levels are significantly higher in African American than White American LN patients in active LN (average 227.8 pg/mL vs. 103.4 pg/mL, p = 0.0309) and during LN remission (average 254.6 pg/mL vs. 89.2 pg/mL, p = 0.0399). Conclusions: Our findings suggest that serum and urine IP-10 measurements provide promising tests for monitoring LN activity, differentiation between classifications of LN, and differentiation between LN and other forms of glomerular disease. We also conclude that further assessment of elevated IP-10 levels in the serum and urine of high-risk populations (i.e., African American) could be beneficial in determining why many of these patients have worse outcomes and are non-responsive to standard therapeutics.
狼疮性肾炎（LN）是系统性红斑狼疮（SLE）常见且严重的并发症。非侵入性诊断方法有限，且当前疗法的有效率不足。趋化因子干扰素-γ诱导蛋白10（IP-10）的表达受干扰素-γ信号传导和核因子κB调控，其分子活性及尿浓度升高与LN有关，但其作为诊断标志物的效用以及与人口统计学、临床或病理特征的关联尚不清楚。方法：纳入38例LN患者和11例患有活动性疾病的非LN肾小球疾病（GD）患者。18例LN患者在研究期间的一次随访中达到缓解。从这些样本中获取血清和尿液，并测量IP-10水平。结果：与正常个体相比，活动性疾病的LN患者血清和尿液IP-10水平显著升高（血清平均179.7 pg/mL vs. 7.2 pg/mL，p < 0.0001；尿液平均28.7 pg/mg vs. 1.6 pg/mg，p = 0.0019），与其他形式的肾小球疾病患者相比也显著升高（血清平均179.7 pg/mL vs. 84.9 pg/mL，p = 0.0176；尿液平均28.7 pg/mg vs. 0.18 pg/mg，p = 0.0011）。增殖性LN（PLN）患者的尿液IP-10水平显著高于膜性LN（MLN）患者（平均32.8 pg/mg vs. 7.6 pg/mg，p = 0.0155）。MLN患者的尿液IP-10水平也高于原发性膜性肾病（MN）患者（平均7.6 pg/mg vs. 0.2 pg/mg，p = 0.0193）。重要的是，在活动性LN和LN缓解期间血清IP-10水平仍保持升高，但72%的患者尿液IP-10水平从活动性LN降至缓解期。最后，在活动性LN和LN缓解期间，非裔美国LN患者的血清IP-10水平显著高于美国白人LN患者（平均227.8 pg/mL vs. 103.4 pg/mL，p = 0.0309；平均254.6 pg/mL vs. 89.2 pg/mL，p = 0.0399），而尿液IP-10水平无显著差异。结论：我们的研究结果表明，血清和尿液IP-10检测为监测LN活动、区分LN分类以及区分LN与其他形式的肾小球疾病提供了有前景的检测方法。我们还得出结论，进一步评估高危人群（即非裔美国人）血清和尿液中升高的IP-10水平可能有助于确定为什么这些患者中的许多人预后较差且对标准治疗无反应。
