Carter Lucy M, Isenberg David A, Ehrenstein Michael R
University College London, London, UK.
Arthritis Rheum. 2013 Oct;65(10):2672-9. doi: 10.1002/art.38074.
To determine whether serum BAFF levels correlate with relapse or remission in patients with systemic lupus erythematosus (SLE) following B cell depletion therapy (BCDT) and to assess the relationship between serum BAFF levels, B cell numbers, and immunoglobulin and autoantibody levels during active disease, both before and after BCDT.
Thirty-five patients with active SLE underwent BCDT with rituximab and were monitored for a minimum of 18 months, using clinical and serologic measures of disease activity. Serum BAFF was measured sequentially by enzyme-linked immunosorbent assay before BCDT and during disease relapse or remission after B cell repopulation.
Serum BAFF levels prior to BCDT correlated positively with the numbers of CD19+ B cells and with the levels of IgG and IgA. Following BCDT and subsequent B cell repopulation, BAFF levels were significantly higher during relapse, as compared with disease remission, and were significantly greater than at disease flare prior to BCDT. At the time of relapse after BCDT, serum BAFF levels were inversely correlated with B cell numbers, with flare at lower B cell numbers being associated with the highest BAFF levels. The correlations between serum BAFF levels and levels of IgG and IgA were lost following BCDT, but changes in serum BAFF levels correlated positively with changes in anti-double-stranded DNA (anti-dsDNA) antibody levels during relapse or remission after BCDT.
The present findings suggest a significant role of BAFF in driving disease flare after B cell repopulation following BCDT. Sequential BCDT may promote ever-increasing levels of BAFF, accompanied by rising anti-dsDNA antibody levels and disease flare even at low B cell numbers. Therefore, our data justify the judicious use of BAFF blockade in a subgroup of lupus patients after BCDT.
确定系统性红斑狼疮（SLE）患者在B细胞清除疗法（BCDT）后血清BAFF水平与疾病复发或缓解是否相关，并评估在BCDT前后疾病活动期血清BAFF水平、B细胞数量以及免疫球蛋白和自身抗体水平之间的关系。
35例活动期SLE患者接受利妥昔单抗BCDT治疗，并使用疾病活动的临床和血清学指标进行至少18个月的监测。在BCDT前以及B细胞重新增殖后疾病复发或缓解期间，通过酶联免疫吸附测定法依次检测血清BAFF水平。
BCDT前血清BAFF水平与CD19+B细胞数量以及IgG和IgA水平呈正相关。BCDT及随后的B细胞重新增殖后，复发期间的BAFF水平显著高于疾病缓解期，且显著高于BCDT前疾病发作时。在BCDT后复发时，血清BAFF水平与B细胞数量呈负相关，较低B细胞数量时的发作与最高BAFF水平相关。BCDT后血清BAFF水平与IgG和IgA水平之间的相关性消失，但在BCDT后复发或缓解期间，血清BAFF水平的变化与抗双链DNA（抗dsDNA）抗体水平的变化呈正相关。
本研究结果表明BAFF在BCDT后B细胞重新增殖后引发疾病发作中起重要作用。序贯BCDT可能会促使BAFF水平不断升高，同时抗dsDNA抗体水平升高，即使在B细胞数量较低时也会引发疾病发作。因此，我们的数据证明在BCDT后的一部分狼疮患者中明智地使用BAFF阻断剂是合理的。
