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Plasma C4d as marker for lupus nephritis in systemic lupus erythematosus

Martin, Myriam LU ; Smolag, Karolina I. LU ; Björk, Albin LU ; Gullstrand, Birgitta LU ; Okrój, Marcin LU ; Leffler, Jonatan; Jönsen, Andreas LU ; Bengtsson, Anders A. LU and Blom, Anna M. LU (2017) In Arthritis Research and Therapy 19(1).
Abstract

Background: In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE). Methods: C4d levels were determined by enzyme-linked immunosorbent assay in plasma samples of patients with established SLE using a novel approach based on detection of a short linear cleavage neoepitope. Cross-sectional associations were studied in 98 patients with SLE with samples taken at lower or higher respective disease activity. Temporal associations were investigated in 69 patients with SLE who were followed longitudinally for up to 5 years. Plasma samples from 77 healthy donors were included as controls. Results: C4d levels were negligible in healthy control... (More)

Background: In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE). Methods: C4d levels were determined by enzyme-linked immunosorbent assay in plasma samples of patients with established SLE using a novel approach based on detection of a short linear cleavage neoepitope. Cross-sectional associations were studied in 98 patients with SLE with samples taken at lower or higher respective disease activity. Temporal associations were investigated in 69 patients with SLE who were followed longitudinally for up to 5 years. Plasma samples from 77 healthy donors were included as controls. Results: C4d levels were negligible in healthy control subjects and significantly increased in patients with SLE in the cross-sectional study (p < 0.0001). C4d levels discriminated between higher and lower disease activity according to ROC curve analysis (p < 0.001), exhibiting a positive predictive value of 68%. At higher disease activity, C4d levels correlated with the modified Systemic Lupus Erythematosus Disease Activity Index (p = 0.011) and predominantly with lupus nephritis (p = 0.003), exhibiting a sensitivity of 79% to identify patients with nephritis. High C4d levels together with the presence of anti-dsDNA autoantibodies preceded and thus predicted future lupus nephritis in the longitudinal study (OR 5.4, 95% CI 1.4-21.3). When we considered only patients with renal involvement (19 of 69) during the longitudinal study, we found that high C4d levels alone could forecast recurrence of future lupus nephritis (OR 3.3, 95% CI 1.2-9.6). Conclusions: C4d appears to be a valuable marker for use in monitoring of patients with SLE, particularly for lupus nephritis. Importantly, C4d levels can predict impending flares of lupus nephritis and may thus be useful for informing treatment.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C4d, Complement, Flare, Lupus nephritis, Systemic lupus erythematosus
in
Arthritis Research and Therapy
volume
19
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85037340511
  • wos:000417526800002
ISSN
1478-6354
DOI
10.1186/s13075-017-1470-2
language
English
LU publication?
yes
id
a70410cf-e808-48de-9aa7-1e9088eca3cf
date added to LUP
2018-01-05 14:23:23
date last changed
2018-01-16 13:29:24
@article{a70410cf-e808-48de-9aa7-1e9088eca3cf,
  abstract     = {<p>Background: In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE). Methods: C4d levels were determined by enzyme-linked immunosorbent assay in plasma samples of patients with established SLE using a novel approach based on detection of a short linear cleavage neoepitope. Cross-sectional associations were studied in 98 patients with SLE with samples taken at lower or higher respective disease activity. Temporal associations were investigated in 69 patients with SLE who were followed longitudinally for up to 5 years. Plasma samples from 77 healthy donors were included as controls. Results: C4d levels were negligible in healthy control subjects and significantly increased in patients with SLE in the cross-sectional study (p &lt; 0.0001). C4d levels discriminated between higher and lower disease activity according to ROC curve analysis (p &lt; 0.001), exhibiting a positive predictive value of 68%. At higher disease activity, C4d levels correlated with the modified Systemic Lupus Erythematosus Disease Activity Index (p = 0.011) and predominantly with lupus nephritis (p = 0.003), exhibiting a sensitivity of 79% to identify patients with nephritis. High C4d levels together with the presence of anti-dsDNA autoantibodies preceded and thus predicted future lupus nephritis in the longitudinal study (OR 5.4, 95% CI 1.4-21.3). When we considered only patients with renal involvement (19 of 69) during the longitudinal study, we found that high C4d levels alone could forecast recurrence of future lupus nephritis (OR 3.3, 95% CI 1.2-9.6). Conclusions: C4d appears to be a valuable marker for use in monitoring of patients with SLE, particularly for lupus nephritis. Importantly, C4d levels can predict impending flares of lupus nephritis and may thus be useful for informing treatment.</p>},
  articleno    = {266},
  author       = {Martin, Myriam and Smolag, Karolina I. and Björk, Albin and Gullstrand, Birgitta and Okrój, Marcin and Leffler, Jonatan and Jönsen, Andreas and Bengtsson, Anders A. and Blom, Anna M.},
  issn         = {1478-6354},
  keyword      = {C4d,Complement,Flare,Lupus nephritis,Systemic lupus erythematosus},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Plasma C4d as marker for lupus nephritis in systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1186/s13075-017-1470-2},
  volume       = {19},
  year         = {2017},
}