银屑病患者关键标志物IL-10/sHLA-G的分析及HLA-G基因中14bp插入/缺失的鉴定。
Analysis of key markers: IL-10/sHLA-G in psoriasis patients and the identification of 14-bp INDEL in the HLA-G gene.
作者信息
Bieniek-Kobuszewska Martyna, Owczarczyk-Saczonek Agnieszka, Maciejewska-Radomska Agata, Wojtacha Paweł, Placek Waldemar
机构信息
Department and Clinic of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, Faculty of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland -
Department and Clinic of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, Faculty of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland.
出版信息
Ital J Dermatol Venerol. 2022 Feb;157(1):62-68. doi: 10.23736/S2784-8671.20.06878-9. Epub 2020 Dec 14.
BACKGROUND
Psoriasis is a chronic inflammation resulting from interactions between immunological and genetic factors. An important tolerogenic role in this autoimmunological disease is played by HLA-G, which is modulated by IL-10. Therefore, this study (N.=80) aimed to evaluate changes in the serum sHLA-G and IL-10 levels in active psoriasis vulgaris and in the early stages of treatment with Methotrexate (MTX) compared to healthy controls. The 14-bp INDEL of the HLA-G gene was evaluated to find possible associations with clinical and laboratory variables.
METHODS
The level of sHLA-G and IL-10 in serum was evaluated (ELISA tests) in patients before the first dose of MTX and at week 12 of treatment, compared to healthy control donors. The 14-bp INDEL in 3'UTR of the HLA-G gene was identified using gDNA templates isolated from full blood. HLA-G amplicons were obtained by PCR, separated by electrophoresis and sequenced.
RESULTS
The mean serum IL-10 level was 4.653±3.33 pg/mL in psoriatic patients, 13.3±9.64 pg/mL after short MTX treatment, compared to 6.23 pg/mL in healthy controls. In addition, the serum level of sHLA-G was 0.275±0.03 ng/mL and 0.332±0.06 ng/mL in patients before and after MTX treatment, respectively, and 0.302±0.08 ng/mL in the control group. A correlation was found (r=-0.43; P<0.005) between the IL-10 and BSA serum levels in psoriasis patients after MTX treatment, indicating health improvement. The three genotypes identified in the 3'UTR of the HLA-G revealed no association with sHLA-G level in serum.
CONCLUSIONS
The mean levels of sHLA-G and the key anti-inflammatory cytokine IL-10 in the blood of pretreatment psoriasis patients are low and indicate that the immunotolerance mechanisms have failed. Treatment of psoriasis patients with low systemic levels of sHLA-G and IL-10 brings them to the same or higher protein levels, respectively, as in healthy donors. Higher sHLA-G levels in healthy donors and after MTX treatment, compared to the sHLA-G levels in the acute phase of psoriasis, indicates its immune system surveillance function.
背景
银屑病是一种由免疫和遗传因素相互作用引起的慢性炎症。HLA-G在这种自身免疫性疾病中发挥着重要的免疫耐受作用，它受白细胞介素-10（IL-10）调节。因此，本研究（N = 80）旨在评估寻常型银屑病患者在疾病活动期及甲氨蝶呤（MTX）治疗早期血清可溶性HLA-G（sHLA-G）和IL-10水平的变化，并与健康对照者进行比较。同时评估HLA-G基因14碱基对插入/缺失多态性（INDEL），以寻找其与临床和实验室变量之间可能存在的关联。
方法
通过酶联免疫吸附测定（ELISA）检测患者在首次服用MTX前及治疗12周时血清中sHLA-G和IL-10水平，并与健康对照者进行比较。采用从全血中分离的基因组DNA模板，鉴定HLA-G基因3'非翻译区（UTR）的14碱基对INDEL。通过聚合酶链反应（PCR）获得HLA-G扩增子，经电泳分离后进行测序。
结果
银屑病患者血清IL-10平均水平为4.653±3.33 pg/mL，短期MTX治疗后为13.3±9.64 pg/mL，而健康对照者为6.23 pg/mL。此外，银屑病患者在MTX治疗前和治疗后血清sHLA-G水平分别为0.275±0.03 ng/mL和0.332±0.06 ng/mL，对照组为0.302±0.08 ng/mL。MTX治疗后银屑病患者血清IL-10水平与体表面积（BSA）之间存在相关性（r = -0.43；P < 0.005）。这表明治疗后患者病情有所改善。在HLA-G基因3'UTR中鉴定出的三种基因型与血清sHLA-G水平无关联。
结论
银屑病患者治疗前血液中sHLA-G和关键抗炎细胞因子IL-10平均水平较低，表明免疫耐受机制失效。对sHLA-G和IL-10全身水平较低的银屑病患者进行治疗，可使他们的蛋白水平分别达到与健康对照者相同或更高的水平。与银屑病急性期的sHLA-G水平相比，健康对照者及MTX治疗后的sHLA-G水平较高，表明其具有免疫系统监测功能。
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