The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjögren's syndrome

Gabriel J. Tobón; Yves Renaudineau; Sophie Hillion; Divi Cornec; Valérie Devauchelle-Pensec; Pierre Youinou; Jacques-Olivier Pers

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The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjögren's syndrome

机译：Fms样酪氨酸激酶3配体是B细胞存活的媒介，也是原发性干燥综合征中淋巴瘤的标志物

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ObjectiveTo determine if the Fms-like tyrosine kinase 3 ligand (Flt-3L), a cytokine implicated in B cell ontogenesis and proliferation in hematologic malignancies, might be responsible for the increased numbers of circulating Bm2 and Bm2′ B cell subsets in patients with primary Sjögren's syndrome (SS).MethodsSerum levels of Flt-3L were measured in 64 patients with primary SS and in 20 healthy controls matched for age and sex. Flt-3L and its receptor Flt-3 were quantified in circulating B cells and in salivary gland (SG) biopsy tissues by immunofluorescence analysis. The effect of Flt-3L on circulating B lymphocytes was then determined by coculture with cells of a human SG (HSG) epithelial cell line.ResultsSerum levels of Flt-3L were increased in patients with primary SS as compared with controls (mean ± SD 135.8 ± 5.5 versus 64.4 ± 4.5 pg/ml; P 0.001). Serum levels of Flt-3L in primary SS patients correlated with the numbers of Bm2 and Bm2′ cells (r = 0.46, P 0.0006), and Flt-3 was selectively expressed in Bm2 and Bm2′ cells. B cell culture experiments showed that Flt-3L potentiated the proliferative effect of anti-IgM stimulation. In SGs, we found that infiltrating B cells expressed Flt-3 and epithelial cells produced Flt-3L. Finally, Flt-3L levels were associated with high disease activity scores and increased risk of developing lymphoma.ConclusionSerum levels of Flt-3L are elevated in patients with primary SS and correlate with abnormal B cell distribution. Flt-3 is mainly expressed by Bm2 and Bm2′ cells. Serum levels of Flt-3L might explain the clinical evolution of primary SS to B cell lymphoma that is observed in some patients, thus opening the possibility of new avenues for therapy.

机译：目的确定Fms样酪氨酸激酶3配体（Flt-3L）是否与血液恶性肿瘤中B细胞的发生和增殖有关，可能是导致原发性患者Bm2和Bm2'B细胞亚群数量增加的原因方法对64名原发性SS患者和20名年龄和性别相匹配的健康对照者进行血清Flt-3L的测定。通过免疫荧光分析定量循环B细胞和唾液腺（SG）活检组织中的Flt-3L及其受体Flt-3。然后通过与人SG（HSG）上皮细胞系细胞共培养来确定Flt-3L对循环B淋巴细胞的影响。结果与对照组相比，原发性SS患者血清Flt-3L的水平升高了（平均值±SD 135.8） ±5.5对64.4±4.5 pg / ml; P <0.001）。原发性SS患者的血清Flt-3L水平与Bm2和Bm2'细胞的数量相关（r = 0.46，P <0.0006），并且Flt-3在Bm2和Bm2'细胞中选择性表达。 B细胞培养实验表明Flt-3L增强了抗IgM刺激的增殖作用。在SGs中，我们发现浸润的B细胞表达Flt-3，而上皮细胞产生Flt-3L。最后，Flt-3L水平与疾病活动评分高和患淋巴瘤的风险增加有关。结论原发性SS患者血清Flt-3L水平升高，且与B细胞分布异常有关。 Flt-3主要由Bm2和Bm2'细胞表达。血清Flt-3L的水平可能解释了在某些患者中观察到的原发性SS到B细胞淋巴瘤的临床演变，从而开辟了新的治疗途径的可能性。

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《Arthritis & Rheumatism》 |2010年第11期|p.3447-3456|共10页
作者
Gabriel J. Tobón; Yves Renaudineau; Sophie Hillion; Divi Cornec; Valérie Devauchelle-Pensec; Pierre Youinou; Jacques-Olivier Pers;
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EA 2216 Immunology and Pathology and IFR 148 ScInBioS, Université de Brest, and Université Européenne de Bretagne, Brest, France;

EA 2216 Immunology and Pathology and IFR 148 ScInBioS, Université de Brest, Université Européenne de Bretagne, and Brest University Medical School Hospital, Brest, France;

EA 2216 Immunology and Pathology and IFR 148 ScInBioS, Université de Brest, and Université Européenne de Bretagne, Brest, France;

Brest University Medical School Hospital, Brest, France;

Brest University Medical School Hospital, Brest, France;

EA 2216 Immunology and Pathology and IFR 148 ScInBioS, Université de Brest, Université Européenne de Bretagne, and Brest University Medical School Hospital, Brest, France;

EA 2216 Immunology and Pathology and IFR 148 ScInBioS, Université de Brest, Université Européenne de Bretagne, and Brest University Medical School Hospital, Brest, France;

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1. Role of Fms-like tyrosine kinase 3 ligand as a potential biologic marker of lymphoma in primary Sj?gren's syndrome [J] . TobónG.J., SarauxA., GottenbergJ.-E., Arthritis and Rheumatism . 2013,第12期

机译：Fms样酪氨酸激酶3配体作为原发性干燥综合征的潜在生物学标志物的作用
2. The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjogren's syndrome. [J] . Tobon GJ, Renaudineau Y, Hillion S, Arthritis and Rheumatism . 2010,第11期

机译：Fms样酪氨酸激酶3配体是B细胞存活的介质，也是原发性干燥综合征中淋巴瘤的标志物。
3. Rapid and significant induction of TRAIL-mediated type II cells in apoptosis of primary salivary epithelial cells in primary Sj?gren’s syndrome [J] . Hideki Nakamura, Atsushi Kawakami, Naoki Iwamoto, Apoptosis . 2008,第11期

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4. Predicting lymphoma outcomes and risk factors in patients with primary Sjögren’s Syndrome using gradient boosting tree ensembles [C] . Vasileios C. Pezoulas, Themis P. Exarchos, Athanasios G. Tzioufas, Annual International Conference of the IEEE Engineering in Medicine and Biology Society . 2019

机译：使用梯度增强树组合预测原发性干燥综合征患者的淋巴瘤结局和危险因素
5. Immunopathogenic Mechanisms in Primary Sj?gren’s Syndrome [D] . Bj?rk, Albin. 2021

机译：原发性SJ的免疫致病机制？GREN的综合征
6. Association between B Cell Growth Factors and Primary Sjögrens Syndrome-Related Autoantibodies in Patients with Non-Hodgkins Lymphoma [O] . Zhenhua Xian, Dehua Fu, Shuang Liu, 2019

机译：非霍奇金淋巴瘤患者中B细胞生长因子与原发性Sjögren综合征相关自身抗体之间的关联
7. The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjögren's syndrome [O] . Gabriel J. Tobón, Yves Renaudineau, Sophie Hillion, 2010

机译：FMS样酪氨酸激酶3配体，B细胞存活的介体，也是原发性Sjögren综合征的淋巴瘤的标志物

The Fms-like tyrosine kinase 3 ligand, a mediator of B cell survival, is also a marker of lymphoma in primary Sjögren's syndrome

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