Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjogren's syndrome
Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjogren's syndrome
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DOI：
10.1111/j.1365-2249.2005.02889.x
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发表时间：
2005-10-01
影响因子：
4.6
通讯作者：
Hurme, M
中科院分区：
文献类型：
--
作者：
Pertovaara, M;Raitala, A;Hurme, M
为了研究色氨酸代谢在原发性干燥综合征 (pSS) 免疫调节中的可能作用，通过反相高效液相色谱 (HPLC) 测量了 103 名 pSS 患者、56 名干燥症状患者和 309 名健康献血者的色氨酸及其代谢物犬尿氨酸的血清浓度。计算了犬尿氨酸与色氨酸的比率 (kyn/trp)，该比率反映了参与色氨酸分解代谢的吲哚胺-吡咯 2,3-双加氧酶 (IDO) 的活性。患有 pSS 的女性和男性患者的血清犬尿氨酸浓度和 kyn/trp 均显着高于有干燥症状的受试者或健康献血者。女性 pSS 患者中犬尿氨酸的中位（四分位数范围）浓度为 2.41 mu mol/l（1.86-3.26），而干燥症状受试者中犬尿氨酸浓度为 1.85 mu mol/l（1.58-2.38，P < 0.0001），健康血液中犬尿氨酸浓度为 1.96 mu mol/l（1.65-2.27，P < 0.0001）捐助者。他们的 kyn/trp x 1000 为 34.0 (25.1-44.3)，而有干燥症状的受试者为 25.3 (21.1-31.5，P < 0.0001)，健康献血者为 24.3 (21.0-28.9，P < 0.0001)。与低IDO活性患者（kyn/trp x 1000 < 34.0）相比，高IDO活性患者（kyn/trp x 1000 >= 34.0）女性pSS患者的ESR、血清C反应蛋白、血清IgA和血清β-2微球蛋白浓度显着较高，血清肌酐水平也较高，抗核抗体阳性的频率更高，符合更多的欧美共识组标准。这些数据表明，依赖于色氨酸分解代谢的机制调节 pSS 中的免疫反应。 pSS 患者的色氨酸降解增强，高 IDO 活性与 pSS 的严重程度相关。
To investigate the possible role of tryptophan metabolism in immune regulation of primary Sjogren's syndrome (pSS) the serum concentrations of tryptophan and its metabolite kynurenine were measured by reverse-phase high-performance liquid chromatography (HPLC) in 103 patients with pSS, 56 patients with sicca symptoms and 309 healthy blood donors. The kynurenine per tryptophan ratio (kyn/trp), which reflects the activity of the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme involved in tryptophan catabolism, was calculated. Both female and male patients with pSS had significantly higher serum kynurenine concentrations and kyn/trp than subjects with sicca symptoms or healthy blood donors. The median (quartile range) concentration of kynurenine in female patients with pSS was 2.41 mu mol/l (1.86-3.26) compared with 1.85 mu mol/l (1.58-2.38, P < 0.0001) in subjects with sicca symptoms and 1.96 mu mol/l (1.65-2.27, P < 0.0001) in healthy blood donors. Their kyn/trp x 1000 was 34.0 (25.1-44.3) compared with 25.3 (21.1-31.5, P < 0.0001) in subjects with sicca symptoms and 24.3 (21.0-28.9, P < 0.0001) in healthy blood donors. Female pSS patients with high IDO activity (kyn/trp x 1000 >= 34.0) had significantly higher ESR, serum C-reactive protein, serum IgA and serum beta-2 microglobulin concentrations as well as higher serum creatinine levels, and they had positive antinuclear antibodies more frequently and presented with more American-European consensus group criteria than those with low IDO activity (kyn/trp x 1000 < 34.0). These data suggest that mechanisms dependent on tryptophan catabolism regulate immune responses in pSS. Tryptophan degradation is enhanced in patients with pSS, and high IDO activity is associated with severity of pSS.