Department of Molecular Biology, The John Paul II Catholic University of Lublin, Konstantynow 1H, 20-708 Lublin, Poland.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159 Mannheim, Germany.
Int J Mol Sci. 2024 Mar 29;25(7):3842. doi: 10.3390/ijms25073842.
Systemic sclerosis (SSc), a predominantly female-affected systemic autoimmune disease, requires tailored treatment strategies contingent on organ involvement and symptom severity. Given SSc's inflammatory nature, the involvement of the kynurenine pathway (KP) in its pathophysiology is underexplored. Our study aimed to investigate sex-related differences in KP activation among SSc patients and assess the impact of angiotensin-converting enzyme (ACE) inhibitors and estimated glomerular filtration rate (eGFR) on KP metabolite concentrations. We enrolled 48 SSc patients and 53 healthy controls, quantifying KP metabolites (tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA)) in serum via high-performance liquid chromatography. Separate multivariate analyses of covariance (MANCOVAs) for women and men were performed to ascertain mean differences between patients and healthy controls while correcting for age. For our secondary objective, we conducted a MANCOVA to explore disparities in ACE inhibitor users and non-users among patients, with BMI correction. Our findings revealed decreased TRP concentrations but increased KYNA/TRP ratio and KYN/TRP ratio in both male and female SSc patients compared to their respective controls. Unlike women, SSc males exhibited higher KYN concentrations and decreased KYNA/KYN ratio relative to their controls. Additionally, SSc patients using ACE inhibitors had higher serum KYNA levels than non-users. Notably, we established a significant correlation between eGFR and KYNA in SSc patients. These results indicate differential KP activation in male and female SSc patients, with males demonstrating heightened KP activation. While ACE inhibitors may influence the KP in SSc patients, further research is necessary to comprehensively understand their impact on symptoms and prognosis in the context of these KP alterations.
系统性硬化症（SSc）是一种主要影响女性的系统性自身免疫性疾病，需要根据器官受累和症状严重程度制定个体化的治疗策略。鉴于 SSc 的炎症性质，其病理生理学中犬尿氨酸途径（KP）的参与尚未得到充分探索。我们的研究旨在调查 SSc 患者中 KP 激活的性别差异，并评估血管紧张素转换酶（ACE）抑制剂和估计的肾小球滤过率（eGFR）对 KP 代谢物浓度的影响。我们招募了 48 名 SSc 患者和 53 名健康对照者，通过高效液相色谱法定量血清中的 KP 代谢物（色氨酸（TRP）、犬尿氨酸（KYN）和犬尿氨酸酸（KYNA））。为了确定患者和健康对照组之间的平均差异，同时校正年龄，我们对女性和男性分别进行了多元协方差分析（MANCOVA）。为了探索我们的次要目标，即患者中 ACE 抑制剂使用者和非使用者之间的差异，我们进行了 MANCOVA，同时进行了 BMI 校正。我们的研究结果表明，与各自的对照组相比，男性和女性 SSc 患者的 TRP 浓度降低，但 KYNA/TRP 比值和 KYN/TRP 比值升高。与女性不同，SSc 男性的 KYN 浓度较高，KYNA/KYN 比值降低。此外，与非使用者相比，使用 ACE 抑制剂的 SSc 患者的血清 KYNA 水平更高。值得注意的是，我们在 SSc 患者中建立了 eGFR 与 KYNA 之间的显著相关性。这些结果表明，男性和女性 SSc 患者的 KP 激活存在差异，男性的 KP 激活程度更高。虽然 ACE 抑制剂可能会影响 SSc 患者的 KP，但需要进一步研究才能全面了解它们在这些 KP 改变的背景下对症状和预后的影响。
