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Measuring plasma C4D to monitor immune complexes in lupus nephritis

OBJECTIVE: Because currently available assays that measure circulating immune complexes (ICx) are suboptimal, a novel assay was recently developed measuring C4d, a stable product of activation of the classical complement pathway. The present study aimed to establish the value of measuring plasma C4d...

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Autores principales: Kraaij, Tineke, Nilsson, Sara C., van Kooten, Cees, Okrój, Marcin, Blom, Anna M, Teng, YK Onno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560920/
https://www.ncbi.nlm.nih.gov/pubmed/31245016
http://dx.doi.org/10.1136/lupus-2019-000326
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author Kraaij, Tineke
Nilsson, Sara C.
van Kooten, Cees
Okrój, Marcin
Blom, Anna M
Teng, YK Onno
author_facet Kraaij, Tineke
Nilsson, Sara C.
van Kooten, Cees
Okrój, Marcin
Blom, Anna M
Teng, YK Onno
author_sort Kraaij, Tineke
collection PubMed
description OBJECTIVE: Because currently available assays that measure circulating immune complexes (ICx) are suboptimal, a novel assay was recently developed measuring C4d, a stable product of activation of the classical complement pathway. The present study aimed to establish the value of measuring plasma C4d levels in a longitudinal cohort of patients with severe refractory SLE who were treated with a combination therapy of rituximab with belimumab (RTX+BLM). METHODS: Fifteen patients with SLE who were treated with RTX+BLM in a phase 2A, open label study were included to sequentially measure plasma C4d levels and correlated to well-established markers of ICx-formation, that is, autoantibodies against double-stranded (ds) DNA, autoantibodies against C1q and proteinuria. The performance of plasma C4d measurements, C4 measurements and the ratio of C4d over C4 (C4d:C4) was evaluated. RESULTS: After establishing that on RTX+BLM treatment kinetics of C4d levels was distinct from traditional C3 and C4 levels, we found strong correlation of C4d:C4 with anti-dsDNA (R=0.76, p<0.001) and anti-C1q (R=0.65, p<0.001) autoantibody levels, which outperformed both stand-alone C4 and C4d levels. Additionally, changes in C4d:C4 over time correlated strongly with changes in proteinuria (R=0.59, p<0.001) as well as anti-dsDNA (R=0.46, p=0.003) and anti-C1q (R=0.47, p=0.002). CONCLUSION: In patients with severe SLE, plasma C4d levels in relation to C4 levels is useful for longitudinal monitoring after RTX+BLM treatment to reflect amelioration of classical complement activation by ICx as well as proteinuria.
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spelling pubmed-65609202019-06-26 Measuring plasma C4D to monitor immune complexes in lupus nephritis Kraaij, Tineke Nilsson, Sara C. van Kooten, Cees Okrój, Marcin Blom, Anna M Teng, YK Onno Lupus Sci Med Brief Communication OBJECTIVE: Because currently available assays that measure circulating immune complexes (ICx) are suboptimal, a novel assay was recently developed measuring C4d, a stable product of activation of the classical complement pathway. The present study aimed to establish the value of measuring plasma C4d levels in a longitudinal cohort of patients with severe refractory SLE who were treated with a combination therapy of rituximab with belimumab (RTX+BLM). METHODS: Fifteen patients with SLE who were treated with RTX+BLM in a phase 2A, open label study were included to sequentially measure plasma C4d levels and correlated to well-established markers of ICx-formation, that is, autoantibodies against double-stranded (ds) DNA, autoantibodies against C1q and proteinuria. The performance of plasma C4d measurements, C4 measurements and the ratio of C4d over C4 (C4d:C4) was evaluated. RESULTS: After establishing that on RTX+BLM treatment kinetics of C4d levels was distinct from traditional C3 and C4 levels, we found strong correlation of C4d:C4 with anti-dsDNA (R=0.76, p<0.001) and anti-C1q (R=0.65, p<0.001) autoantibody levels, which outperformed both stand-alone C4 and C4d levels. Additionally, changes in C4d:C4 over time correlated strongly with changes in proteinuria (R=0.59, p<0.001) as well as anti-dsDNA (R=0.46, p=0.003) and anti-C1q (R=0.47, p=0.002). CONCLUSION: In patients with severe SLE, plasma C4d levels in relation to C4 levels is useful for longitudinal monitoring after RTX+BLM treatment to reflect amelioration of classical complement activation by ICx as well as proteinuria. BMJ Publishing Group 2019-06-03 /pmc/articles/PMC6560920/ /pubmed/31245016 http://dx.doi.org/10.1136/lupus-2019-000326 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Brief Communication
Kraaij, Tineke
Nilsson, Sara C.
van Kooten, Cees
Okrój, Marcin
Blom, Anna M
Teng, YK Onno
Measuring plasma C4D to monitor immune complexes in lupus nephritis
title Measuring plasma C4D to monitor immune complexes in lupus nephritis
title_full Measuring plasma C4D to monitor immune complexes in lupus nephritis
title_fullStr Measuring plasma C4D to monitor immune complexes in lupus nephritis
title_full_unstemmed Measuring plasma C4D to monitor immune complexes in lupus nephritis
title_short Measuring plasma C4D to monitor immune complexes in lupus nephritis
title_sort measuring plasma c4d to monitor immune complexes in lupus nephritis
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560920/
https://www.ncbi.nlm.nih.gov/pubmed/31245016
http://dx.doi.org/10.1136/lupus-2019-000326
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