Aksan Aysegül, Tugal Dilem, Hein Nathalena, Boettger Katharina, Caicedo-Zea Yurani, Diehl Ina, Schumann Claudia, Armbruster Franz-Paul, Stein Jürgen
Interdisciplinary Crohn Colitis Center Rhein-Main, Schifferstr. 59, 60594 Frankfurt am Main, Germany.
Institute of Pharmaceutical Chemistry, Goethe University, 60438 Frankfurt am Main, Germany.
J Clin Med. 2020 Feb 17;9(2):547. doi: 10.3390/jcm9020547.
Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4-67.3) vs. 18.5 (1.2-51.0) pg/mL, < 0.001) and VDBP (351.2 (252.2-530.6) vs. 330.8 (183.5-560.3) mg/dL, < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (-0.155, = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, = 0.049), transferrin (0.160, = 0.037) and hsCRP (0.261, < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (-0.165, = 0.031, -0.205, < 0.001, respectively) and hsCRP (-0.164, = 0.032, -0.208, < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (-0.377, = 0.028, -0.409, < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.
近期研究获得的证据引发了人们对维生素D在骨骼外功能（如炎症和免疫调节）中作用的越来越多的关注。尽管维生素D缺乏与包括炎症性肠病（IBD）在内的炎症性疾病的病理生理学有关，但关于补充维生素D是否可以治愈或预防慢性病的证据并不一致。由于25羟维生素D（25OHD）被认为是一种急性期蛋白，因此其作为维生素D状态标志物的效用值得怀疑。在本研究中，对188例IBD患者中维生素D与炎症之间可能的相互作用进行了研究，将高敏C反应蛋白（hsCRP）水平≥5mg/dL和/或粪便钙卫蛋白≥250μg/g定义为炎症活动的生化证据。采用酶联免疫吸附测定法（ELISA）测定25OHD和维生素D结合蛋白（VDBP）水平，采用液相色谱-串联质谱法（LC-MS/MS）测定1,25-二羟维生素D（1,25OHD）和24,25-二羟维生素D（24,25OHD）水平。使用经验证的比克尔公式计算游离和生物可利用的维生素D水平。炎症组和非炎症组的血清1,25OH2D和维生素D结合蛋白（VDBP）水平存在差异：有炎症疾病活动的患者血清1,25OH2D（35.0（16.4 - 67.3）对18.5（1.2 - 51.0）pg/mL，P < 0.001）和VDBP（351.2（252.2 - 530.6）对330.8（183.5 - 560.3）mg/dL，P < 0.05）浓度显著高于无活动性炎症的患者。血清24,25OH2D水平与红细胞沉降率（ESR）呈负相关（-0.155，P = 0.049），而血清1,25OH2D浓度与hsCRP呈正相关（0.157，P = 0.036）。发现ESR（0.150，P = 0.049）、转铁蛋白（0.160，P = 0.037）和hsCRP（0.261，P < 0.001）与血清VDBP水平相关。血清游离和生物可利用的25OHD水平与ESR（分别为-0.165，P = 0.031，-0.205，P < 0.001）和hsCRP（分别为-0.164，P = 0.032，-0.208，P < 0.001）呈负相关，与粪便钙卫蛋白呈中度负相关（分别为-0.377，P = 0.028，-0.409，P < 0.016）。血清总25OHD浓度是唯一未发现与任何炎症标志物有特定相关性的维生素D参数。根据这些结果，传统参数总25OHD似乎仍然是炎症性肠病患者中维生素D状态的最佳标志物，无论是否存在炎症。
