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原发性干燥综合征中从良性淋巴增生到恶性 B 细胞淋巴瘤的胸腺基质淋巴细胞生成素表达。

Thymic stromal lymphopoietin expression from benign lymphoproliferation to malignant B-cell lymphoma in primary Sjögren's syndrome.

机构信息

Rheumatology Clinic, Udine University Hospital, Department of Medical Area, University of Udine, Italy.

Institute of Anatomic Pathology, Udine University Hospital, Department of Medical Area, University of Udine, Italy.

出版信息

Clin Exp Rheumatol. 2019 May-Jun;37 Suppl 118(3):55-64. Epub 2019 Aug 27.

PMID:31464668
Abstract

OBJECTIVES

To investigate the expression of thymic stromal lymphopoietin (TSLP) in primary Sjögren's syndrome (pSS), stratified according to the lymphoproliferative status, from a fully benign (fbSS) stage to myoepithelial sialadenitis (MESA) and to B-cell non-Hodgkin's lymphoma (NHL).

METHODS

After initial serum studies in large numbers of pSS patients and in controls, TSLP was investigated also in pathologic salivary glands (SG) biopsies from 38 stratified pSS patients (13 fbSS; 13 MESA; 12 NHL) and from 13 controls with non-autoimmune sicca syndrome (nSS) by RT-PCR, immunohistochemistry and immunofluorescence.

RESULTS

Significantly higher TSLP serum levels were shown in pSS than controls, increasing from fbSS to MESA and to NHL. In SG biopsies, TSLP-positive B lymphocytes increased with increasing lymphoproliferation, maximally in NHL, consistent with the detection of inducible TSLP long isoform (lfTSLP) mRNA only in MESA and NHL. By contrast, the constitutive TSLP short isoform (sfTSLP) mRNA showed no difference among subgroups. The TSLP expression by glandular epithelium declined with the progression from fbSS to MESA and to NHL.

CONCLUSIONS

TSLP progressively increases from benign to malignant B-cell lymphoproliferation in pSS. The salivary epithelium expresses TSLP but, with the progression of lymphoproliferation, the B-cells may represent the major source of TSLP, in its long inducible isoform. A possible pathogenetic role of TSLP is herein hypothesised in pSS for the first time. Further analyses on TSLP, also as a biomarker of pSS and related lymphoproliferation, are worthwhile.

摘要

目的

根据增殖状态,从完全良性(fbSS)阶段到肌上皮涎腺炎(MESA)和 B 细胞非霍奇金淋巴瘤(NHL),研究胸基质淋opoietin(TSLP)在原发性干燥综合征(pSS)中的表达。

方法

在大量 pSS 患者和对照者的初步血清研究之后,还通过 RT-PCR、免疫组织化学和免疫荧光法研究了 38 例分层 pSS 患者(13 例 fbSS;13 例 MESA;12 例 NHL)和 13 例非自身免疫干燥综合征(nSS)对照者的病理唾液腺(SG)活检中的 TSLP。

结果

pSS 患者的 TSLP 血清水平明显高于对照组,从 fbSS 增加到 MESA 和 NHL。在 SG 活检中,随着淋巴增殖的增加,TSLP 阳性 B 淋巴细胞增加,在 NHL 中最大,与仅在 MESA 和 NHL 中检测到诱导性 TSLP 长同工型(lfTSLP)mRNA 一致。相比之下,组成性 TSLP 短同工型(sfTSLP)mRNA 在亚组之间无差异。从 fbSS 到 MESA 和 NHL,腺体上皮的 TSLP 表达逐渐下降。

结论

TSLP 在 pSS 的良性至恶性 B 细胞淋巴增殖中逐渐增加。唾液腺上皮表达 TSLP,但随着淋巴增殖的进展,B 细胞可能是 TSLP 的主要来源,其长诱导同工型。本文首次假设 TSLP 在 pSS 中具有潜在的发病机制作用。进一步分析 TSLP 作为 pSS 和相关淋巴增殖的生物标志物是值得的。

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