Abstract
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 °C) in the CureJM Center’s BioRepository. Serum BAFF was quantitated by Mesoscale® technology. Oligoclonal B cell expansion was defined as a CJ:KREC ≥ 8 prior to Rituximab therapy. Detection of a CJ:KREC ratio ≤ 2.5 in the first sample after Rituximab was designated as adequate B cell depletion. A significant clinical response to therapy was defined as improvement in Disease Activity Score (DAS) by at least 2 points on consecutive visits within the first 12 months of therapy. Results: Six out of nine children with JDM showed oligoclonal B cell expansion prior to Rituximab (CJ:KREC ≥ 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.
Original language | English (US) |
---|---|
Article number | 36 |
Journal | BMC Rheumatology |
Volume | 6 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2022 |
Funding
The authors wish to acknowledge CARRA and the ongoing Arthritis Foundation financial support of CARRA. This study was funded by the Children’s Arthritis and Rheumatology Research Alliance (CARRA) and the Arthritis Foundation (to A.K.) and The Cure-JM Foundation (to L.P.). E.O. is partially supported by a National Institute of Health grant: T32AI083216, Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine. This content is solely the responsibilities of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agencies did not have any role in the design of the study, collection, analysis, and interpretation of data and in the manuscript writing.
Keywords
- BAFF level
- Juvenile dermatomyositis
- KREC evaluation
- Rituximab response
ASJC Scopus subject areas
- Rheumatology
Fingerprint
Dive into the research topics of 'Coding joint: kappa-deleting recombination excision circle ratio and B cell activating factor level: predicting juvenile dermatomyositis rituximab response, a proof-of-concept study'. Together they form a unique fingerprint.Datasets
-
Coding joint: kappa-deleting recombination excision circle ratio and B cell activating factor level: predicting juvenile dermatomyositis rituximab response, a proof-of-concept study
Ochfeld, E. (Creator), Hans, V. (Creator), Marin, W. (Creator), Ahsan, N. (Creator), Morgan, G. (Creator), Pachman, L. M. (Creator) & Khojah, A. (Creator), figshare, 2022
DOI: 10.6084/m9.figshare.c.5985233, https://springernature.figshare.com/collections/Coding_joint_kappa-deleting_recombination_excision_circle_ratio_and_B_cell_activating_factor_level_predicting_juvenile_dermatomyositis_rituximab_response_a_proof-of-concept_study/5985233
Dataset