Expression of APRIL in Diffuse Large B Cell Lymphomas from Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis
Expression of APRIL in Diffuse Large B Cell Lymphomas from Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis
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DOI：
10.3899/jrheum.101190
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发表时间：
2011-09-01
影响因子：
3.9
通讯作者：
Baecklund, Eva
中科院分区：
文献类型：
--
作者：
Lofstrom, Bjorn;Backlin, Carin;Baecklund, Eva
目标。类风湿关节炎(RA)和系统性红斑狼疮(SLE)患者患弥漫性大B细胞淋巴瘤(DLBCL)的风险增加。细胞因子A增殖诱导配体(APRIL)在普通人群的DLBCL中高表达，并在RA和SLE患者亚群的血清中检测到高浓度。为了研究APRIL和DLBCL在RA和SLE中的可能相关性，我们检测了来自RA和SLE患者以及非炎症性疾病的DLBCL患者淋巴瘤活检组织中APRIL的表达。对95例RA、12例SLE和63例对照DLBCL的淋巴瘤组织进行抗APRLY-2抗体染色。对照病例的阳性细胞百分比被分成四分位数(1-4，其中4=染色最多)，并与RA和SLE淋巴瘤的结果进行比较。APRIL的表达与临床变量相关。在SLE DLBCL中高表达APRIL的优势比(OR23.6，95%CI2.4~231.2)显著高于RA DLBCL(OR0.8，95%CI0.3~2.0)。四分位数4的RA患者的累积RA疾病活动度高于四分位数I的患者(p=0.013)。淋巴瘤组织中的EB病毒与APRIL的高表达有关(p=0.009)。在SLE和RA亚群中，APRIL在DLBCL中的高表达可能表明APRIL与这些风湿性疾病亚群中的淋巴瘤有关，但也可能反映了这些患者组中APRIL本身的失调。(2011年7月1日首次发布；J Rheumatol 2011年；38：1891-7；DOI：10.3899/jrangum.101190)
Objective. Patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have an increased risk of diffuse large B cell lymphoma (DLBCL). The cytokine A PRoliferating-Inducing Ligand (APRIL) is strongly expressed in DLBCL in the general population and is detected in high concentrations in sera from subgroups of patients with RA and SLE. To investigate a possible association between APRIL and DLBCL in RA and SLE, we examined APRIL expression in lymphoma biopsies from patients with RA and SLE and from DLBCL patients without inflammatory disease.Methods. Lymphoma tissue from 95 RA, 12 SLE, and 63 comparator DLBCL cases were stained with anti-APRIL antibodies (Aprily-2). The percentage of positively stained cells of the comparator cases were divided into quartiles (1-4, where 4 = most stained) and compared with the results for the RA and SLE lymphomas. APRIL expression was correlated to clinical variables.Results. The odds ratio for high expression of APRIL (quartiles 3 and 4) was elevated in the SLE DLBCL (OR 23.6, 95% CI 2.4-231.2), but not in the RA DLBCL (OR 0.8, 95% CI 0.3-2.0). RA patients in quartile 4 had higher cumulated RA disease activity than those in quartile I (p = 0.013). Epstein-Barr virus in the lymphoma tissue was associated with high APRIL expression (p = 0.009).Conclusion. The high expression of APRIL in DLBCL in SLE and in an RA subset might indicate an association between APRIL and lymphoma in these subsets of rheumatic diseases, but could also reflect a dysregulation of APRIL per se in these patient groups. (First Release July 1 2011; J Rheumatol 2011;38:1891-7; doi:10.3899/jrheum.101190)