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

Elisa Ochfeld; Victoria Hans; Wil Marin; Najah Ahsan; Gabrielle Morgan; Lauren M. Pachman; Amer Mohammad Khojah

doi:10.1186/s41927-022-00265-z

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

Elisa Ochfeld, Victoria Hans, Wil Marin, Najah Ahsan, Gabrielle Morgan, Lauren M. Pachman, Amer Mohammad Khojah^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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	https://doi.org/10.1186/s41927-022-00265-z
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

Access to Document

10.1186/s41927-022-00265-z

Cite this

@article{e67b15ae34844f5793a2d1f1be6d9ba9,

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

abstract = "Background: This pilot study{\textquoteright}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{\textquoteright}s BioRepository. Serum BAFF was quantitated by Mesoscale{\textregistered} 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.",

keywords = "BAFF level, Juvenile dermatomyositis, KREC evaluation, Rituximab response",

author = "Elisa Ochfeld and Victoria Hans and Wil Marin and Najah Ahsan and Gabrielle Morgan and Pachman, {Lauren M.} and Khojah, {Amer Mohammad}",

note = "Funding Information: The authors wish to acknowledge CARRA and the ongoing Arthritis Foundation financial support of CARRA. This study was funded by the Children{\textquoteright}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. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s41927-022-00265-z",

language = "English (US)",

volume = "6",

journal = "BMC Rheumatology",

issn = "2520-1026",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Coding joint

T2 - kappa-deleting recombination excision circle ratio and B cell activating factor level: predicting juvenile dermatomyositis rituximab response, a proof-of-concept study

AU - Ochfeld, Elisa

AU - Hans, Victoria

AU - Marin, Wil

AU - Ahsan, Najah

AU - Morgan, Gabrielle

AU - Pachman, Lauren M.

AU - Khojah, Amer Mohammad

N1 - Funding Information: 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. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - BAFF level

KW - Juvenile dermatomyositis

KW - KREC evaluation

KW - Rituximab response

UR - http://www.scopus.com/inward/record.url?scp=85129705401&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85129705401&partnerID=8YFLogxK

U2 - 10.1186/s41927-022-00265-z

DO - 10.1186/s41927-022-00265-z

M3 - Article

C2 - 35527253

AN - SCOPUS:85129705401

SN - 2520-1026

VL - 6

JO - BMC Rheumatology

JF - BMC Rheumatology

IS - 1

M1 - 36

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint