Developing biomarkers for predicting clinical relapse in pemphigus patients treated with rituximab

作者：Albers Lauren N; Liu Yuan; Bo Na; Swerlick Robert A; Feldman Ron J

来源：Journal of the American Academy of Dermatology, 2017, 77(6): 1074-1082.

DOI：10.1016/j.jaad.2017.07.012

• autoantibodies
• autoimmune bullous diseases
• immunology
• pemphigus
• pemphigus foliaceus
• pemphigus vulgaris
• prediction
• relapse
• rituximab

Background: Rituximab is an effective therapy for pemphigus, although relapses are common.
Objective: To identify biomarkers to predict relapse of pemphigus following rituximab treatment.
Methods: 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.
Results: Relapse was rare before B-cell repopulation. Univariate analysis revealed low CD4 count (<400 cells/mu L) 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: Limitations include the retrospective design and inconsistent follow-up.
Conclusion: Relapse is associated with B-cell repopulation, low CD4(+) T-cell count, and positive result of testing for Dsg1 and Dsg3.

• 出版日期2017-12