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骨膜蛋白在未受累皮肤中的表达作为系统性硬化症患者皮肤快速进展的潜在生物标志物:一项初步探索性研究。

Periostin expression in uninvolved skin as a potential biomarker for rapid cutaneous progression in systemic sclerosis patients: a preliminary explorative study.

作者信息

De Luca Giacomo, Campochiaro Corrado, Burastero Samuele E, Matucci-Cerinic Marco, Doglioni Claudio, Dagna Lorenzo

机构信息

Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy.

School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

出版信息

Front Med (Lausanne). 2024 Jan 24;10:1214523. doi: 10.3389/fmed.2023.1214523. eCollection 2023.

Abstract

OBJECTIVES

This study aimed to evaluate periostin serum levels and skin expression in patients with systemic sclerosis (SSc).

METHODS

We enrolled 35 patients with diffuse (d-SSc) or limited (l-SSc) SSc, 15 patients with very early diagnosis of systemic sclerosis (VEDOSS), and 30 sex-matched healthy controls. Periostin serum levels were determined by an enzyme-linked immunosorbent assay (ELISA). Periostin skin expression was determined by immunohistochemistry (IHC) on paired involved and uninvolved 5-mm skin biopsy samples in a subgroup of 10 d-SSc and 10 L-SSc patients. A 12-month follow-up was considered.

RESULTS

We included 50 patients (mean age 53.1 ± 16.1 years; women 94%; mean disease duration 38.2 ± 45.1 months; anti-centromere 50%; anti-Scl70 40%), 35 of them with a definite SSc (68.8% l-SSc; 31.4% d-SSc; mean mRSS 9.0 ± 7.2) and 15 with VEDOSS; 30 controls were also included in this study. Periostin serum levels were higher in SSc patients compared to controls (32.7 ± 8.0 ng/mL vs. 27.7 ± 7.3 ng/mL;  < 0.001), while these levels were comparable among different groups of patients (29.7 ± 6.9 ng/mL in VEDOSS, 33.4 ± 7.8 ng/mL in lc-SSc; and 34.0 ± 8.5 in dc-SSc;  = ns). SSc patients with digital ulcers had higher periostin serum levels (36.2 ± 7.9 ng/mL vs. 30.6 ± 7.3 ng/mL,  < 0.02). Samples from the involved skin of l-SSc and d-SSc patients showed a significant dermal expression of periostin; an identical periostin expression was evident in the uninvolved skin of patients with d-SSc. In 7 out of 10 L-SSc patients, periostin expression was absent on uninvolved skin. In the remaining three l-SSc patients, a mild periostin expression on IHC was detectable on uninvolved skin and all of these three l-SSc patients presented a dramatic skin progression.

CONCLUSION

Periostin skin expression may be a useful biomarker to indicate the presence of a disease at a higher risk of rapid cutaneous involvement.

摘要

目的

本研究旨在评估系统性硬化症(SSc)患者血清骨膜蛋白水平及皮肤表达情况。

方法

我们纳入了35例弥漫性(d-SSc)或局限性(l-SSc)SSc患者、15例极早期诊断的系统性硬化症(VEDOSS)患者以及30例性别匹配的健康对照者。采用酶联免疫吸附测定(ELISA)法测定血清骨膜蛋白水平。在10例d-SSc和10例l-SSc患者的亚组中,通过免疫组织化学(IHC)法对配对的5mm受累及未受累皮肤活检样本进行骨膜蛋白皮肤表达检测。进行为期12个月的随访。

结果

我们纳入了50例患者(平均年龄53.1±16.1岁;女性占94%;平均病程38.2±45.1个月;抗着丝点抗体阳性率50%;抗Scl70抗体阳性率40%),其中35例为确诊的SSc(68.8%为l-SSc;31.4%为d-SSc;平均改良Rodnan皮肤评分9.0±7.2),15例为VEDOSS;本研究还纳入了30例对照者。与对照组相比,SSc患者血清骨膜蛋白水平更高(32.7±8.0ng/mL vs. 27.7±7.3ng/mL;P<0.001),而不同患者组之间这些水平相当(VEDOSS组为29.7±6.9ng/mL,lc-SSc组为33.4±7.8ng/mL,dc-SSc组为34.0±8.5ng/mL;P=无统计学意义)。有指端溃疡的SSc患者血清骨膜蛋白水平更高(36.2±7.9ng/mL vs. 30.6±7.3ng/mL,P<0.02)。l-SSc和d-SSc患者受累皮肤样本显示骨膜蛋白有显著的真皮表达;d-SSc患者未受累皮肤也有相同的骨膜蛋白表达。10例l-SSc患者中有7例未受累皮肤无骨膜蛋白表达。其余3例l-SSc患者未受累皮肤在免疫组织化学上可检测到轻度骨膜蛋白表达,且这3例l-SSc患者均出现了明显的皮肤进展。

结论

骨膜蛋白皮肤表达可能是一种有用的生物标志物,可用于指示疾病的存在,提示有快速皮肤受累的较高风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7769/10847316/c06a4e5087ab/fmed-10-1214523-g001.jpg

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