Rheumatology Clinic, Udine University Hospital, Department of Medical Area, University of Udine, Italy.
Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Greece.
Clin Exp Rheumatol. 2020 Jul-Aug;38 Suppl 126(4):189-194. Epub 2020 Oct 23.
Thymic stromal lymphopoietin (TSLP) has been implicated in primary Sjögren's syndrome (pSS) and related B-cell lymphoproliferation and lymphoma (NHL) by studies on salivary pathologic tissues and serum. The purpose of this work was to validate serum TSLP as biomarker of pSS and related lymphoproliferation by the study of two additional independent cohorts.
Serum TSLP was measured by ELISA in the original published Cohort-1 from Udine, Italy, including 91 patients. Two additional cohorts were then studied for validation: Cohort-2, including 4 sub-cohorts comprising 125 patients from the Universities of Roma, L'Aquila, Pisa and Perugia, belonging to the Italian SS Study Group (GRISS), and Cohort-3, including 59 patients from the University of Athens, Greece. Overall, 159 control subjects were enrolled. Active pSS-NHL, as well as pre-lymphomatous conditions, i.e. persistent salivary gland swelling and mixed cryoglobulinaemia, were investigated in detail. In addition, serum samples from pSS-NHL in complete remission were analysed (n=27).
TSLP serum levels were confirmed to be significantly higher in pSS compared to controls in both Cohort-2 and Cohort-3, in particular in patients with lymphoproliferation. Serum TSLP was much higher in pSS pre-lymphomatous conditions. Finally, active NHL showed the highest TSLP serum levels, while in NHL in remission TSLP resulted undetectable or significantly lower than in benign pSS.
By the study of independent cohorts, it was again demonstrated that serum TSLP levels are increased in pSS, above all in more advanced B-cell lymphoproliferation and NHL. Serum TSLP can therefore represent a novel biomarker for pSS-related lymphoproliferation.
研究人员通过对唾液病理组织和血清的研究发现，胸腺基质淋巴细胞生成素（TSLP）与原发性干燥综合征（pSS）及相关 B 细胞淋巴增生和淋巴瘤（NHL）有关。本研究旨在通过对另外两个独立队列的研究，验证血清 TSLP 是否可作为 pSS 及相关淋巴增生的生物标志物。
通过 ELISA 法检测意大利乌迪内队列 1 中 91 例患者的血清 TSLP，然后对另外两个队列进行验证：队列 2 包括来自罗马大学、拉奎拉大学、比萨大学和佩鲁贾大学的意大利 SS 研究组（GRISS）的 125 例患者的 4 个亚队列，队列 3 包括来自希腊雅典大学的 59 例患者。共纳入 159 例对照者。详细研究了活动性 pSS-NHL 以及前淋巴肿瘤状态，即持续性唾液腺肿胀和混合性冷球蛋白血症。此外，还分析了 pSS-NHL 完全缓解患者的血清样本（n=27）。
在队列 2 和队列 3 中，与对照组相比，pSS 患者的 TSLP 血清水平均显著升高，尤其是在存在淋巴增生的患者中。在前淋巴肿瘤状态的 pSS 患者中，血清 TSLP 水平更高。最后，活动性 NHL 的 TSLP 血清水平最高，而缓解期 NHL 的 TSLP 水平则无法检测或显著低于良性 pSS。
通过对独立队列的研究，再次证明 pSS 患者的血清 TSLP 水平升高，尤其是在更晚期的 B 细胞淋巴增生和 NHL 中。因此，血清 TSLP 可以作为 pSS 相关淋巴增生的新型生物标志物。
