Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
J Am Acad Dermatol. 2017 Dec;77(6):1074-1082. doi: 10.1016/j.jaad.2017.07.012. Epub 2017 Sep 18.
Rituximab is an effective therapy for pemphigus, although relapses are common.
To identify biomarkers to predict relapse of pemphigus following rituximab treatment.
In this retrospective cohort study, 62 patients with pemphigus treated with 99 rituximab cycles provided longitudinal clinical scoring and biomarker data, including levels of CD19 B cells, CD4 T cells, and desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) autoantibodies. An extended time-variant Kaplan-Meier estimator and extended Cox model were applied.
Relapse was rare before B-cell repopulation. Univariate analysis revealed low CD4 count (<400 cells/μL) to predict relapse (P < .001). A positive result of testing for Dsg1 (>20 IU) was predictive of relapse among patients with mucocutaneous disease (hazard ratio, 6.40; P = .019); a positive result of testing for Dsg3 (>20 IU) was predictive in patients with mucocutaneous and mucosal disease (hazard ratio, 32.92; P < .001). Multivariable analysis revealed that every CD4 value increase of 200 decreases the hazard ratio for relapse by 35% (P = .029). A positive result of testing for Dsg1 increases the risk for relapse by a factor of 12.32 in patients with mucocutaneous disease (P = .001); positive result of testing for Dsg3 increases risk for relapse by 28.38 in patients with mucosal and mucocutaneous disease (P = .006).
Limitations include the retrospective design and inconsistent follow-up.
Relapse is associated with B-cell repopulation, low CD4 T -cell count, and positive result of testing for Dsg1 and Dsg3.
利妥昔单抗是治疗天疱疮的有效疗法,尽管复发很常见。
确定生物标志物以预测利妥昔单抗治疗后天疱疮的复发。
在这项回顾性队列研究中,62 例接受利妥昔单抗治疗的天疱疮患者提供了纵向临床评分和生物标志物数据,包括 CD19 B 细胞、CD4 T 细胞以及桥粒芯糖蛋白 1(Dsg1)和桥粒芯糖蛋白 3(Dsg3)自身抗体的水平。应用扩展时变 Kaplan-Meier 估计量和扩展 Cox 模型。
在 B 细胞再增殖之前,复发很少见。单因素分析显示,CD4 计数低(<400 个/μL)预测复发(P<0.001)。黏膜疾病患者 Dsg1 检测阳性(>20 IU)预测复发(危险比,6.40;P=0.019);黏膜和黏膜疾病患者 Dsg3 检测阳性(>20 IU)预测复发(危险比,32.92;P<0.001)。多变量分析显示,CD4 值每增加 200,复发的危险比降低 35%(P=0.029)。黏膜疾病患者 Dsg1 检测阳性,复发风险增加 12.32 倍(P=0.001);黏膜和黏膜疾病患者 Dsg3 检测阳性,复发风险增加 28.38 倍(P=0.006)。
局限性包括回顾性设计和不一致的随访。
复发与 B 细胞再增殖、CD4 T 细胞计数低以及 Dsg1 和 Dsg3 检测阳性有关。