Salazar-Camarena D C, Ortiz-Lazareno P C, Cruz A, Oregon-Romero E, Machado-Contreras J R, Muñoz-Valle J F, Orozco-López M, Marín-Rosales M, Palafox-Sánchez C A
Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social IMSS, Guadalajara, Jalisco, México.
Lupus. 2016 May;25(6):582-92. doi: 10.1177/0961203315608254. Epub 2015 Sep 29.
B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE).
BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38-/ + naïve; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs).
Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower BCMA expression was associated with severe disease activity, glomerulonephritis, serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative correlation with Mex-SLEDAI score (r = -0.494, p = 0.006).
Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients.
B细胞活化因子（BAFF）和增殖诱导配体（APRIL）信号通路通过与其受体BAFF-R、TACI和BCMA相互作用来调节B细胞存活。我们根据系统性红斑狼疮（SLE）的临床表现评估了这些配体/受体在B细胞亚群上的关联。
采用酶联免疫吸附测定法检测30例SLE患者血清中BAFF和APRIL的浓度。通过流式细胞术分析每个B细胞亚群（CD19+CD27-CD38-/+幼稚细胞；CD19+CD27+CD38-/+记忆细胞；CD19+CD27-CD38++未成熟细胞和CD19+CD27+CD38++浆细胞）上BAFF-R、TACI和BCMA的表达，并在不同临床表现的患者以及健康对照（HCs）之间进行比较。
SLE患者血清BAFF和APRIL水平较高，且与墨西哥SLE疾病活动指数相关（r = 0.584；p = 0.001和r = 0.456；p = 0.011）。SLE患者的记忆B细胞和浆细胞比例增加（p < 0.05）。与HCs相比，SLE患者几乎所有B细胞亚群中BAFF-R、TACI和BCMA的表达均降低（p < 0.05）。较低的BCMA表达与严重疾病活动、肾小球肾炎、浆膜炎和溶血性贫血相关（p < 0.01）。BCMA表达与墨西哥SLEDAI评分呈负相关（r = -0.494，p = 0.006）。
根据严重疾病活动情况，外周B细胞上BCMA表达降低表明BCMA在SLE患者B细胞过度活化和免疫耐受稳态中起重要调节作用。
