Coding joint: kappa-deleting recombination excision circle ratio and B cell activating factor level: predicting juvenile dermatomyositis rituximab response, a proof-of-concept study

摘要

Background This pilot study's primary aim was to determine if oligoclonal B cell expansion in children with Juvenile Dermatomyositis (JDM) predicts response to Rituximab therapy. We evaluated: (1) tissue B cell depletion efficacy by measuring the ratio of Coding joint (CJ) to Kappa-deleting recombination excision circle (KREC) DNA, and (2) serum BAFF level upon B cell recovery. Methods CJ and KREC values were measured via qPCR assessment of serial PBMC stored (- 80 degrees C) in the CureJM Center's BioRepository. Serum BAFF was quantitated by Mesoscale (R) technology. Oligoclonal B cell expansion was defined as a CJ:KREC >= 8 prior to Rituximab therapy. Detection of a CJ:KREC ratio = 8). Of those 6 patients, 4 had evidence of effective B cell depletion after Rituximab (CJ:KREC <= 2.5), and all 4 of those subjects displayed a significant clinical response to Rituximab. Serum BAFF level increased in 8/9 children after Rituximab. Conclusions In this proof-of-concept study, JDM patients with oligoclonal B cell expansion prior to Rituximab have more favorable clinical outcomes after Rituximab. We speculate: (1) B cell depletion post-Rituximab predicts JDM clinical response; (2) increased BAFF post-Rituximab may contribute to disease flare.