Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT

Clara Mistegaard; Anne Troldborg; Murat Torgutalp; Anne Gitte Loft; Steffen Thiel; Burkhard Muche; Valeria Rios Rodriguez; Mikhail Protopopov; Joachim Listing; Joachim Sieper; Denis Poddubnyy; Fabian Proft

doi:10.1093/rap/rkaf007

Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT

Clara Mistegaard, Anne Troldborg, Murat Torgutalp, Anne Gitte Loft, Steffen Thiel, Burkhard Muche, Valeria Rios Rodriguez, Mikhail Protopopov, Joachim Listing, Joachim Sieper, Denis Poddubnyy, Fabian Proft

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Objectives: To investigate lectin pathway proteins (LPPs) and complement activation marker C3dg as biomarkers for disease activity and treatment response in a multicentre, randomized controlled trial of axial spondyloarthritis (axSpA) patients initiating TNF inhibitor (TNFi) therapy. Methods: Serum samples from 108 patients with active radiographic axSpA from the CONSUL study, collected before and after 12 weeks of TNFi therapy, were measured using immunoassays for LPPs (MBL, CL-L1, M-, L-, and H-ficolin, MASP-1, -2, and -3, MAp44) and the complement activation marker C3dg. Results: After 12 weeks of TNFi therapy, serum levels of LPPs L-ficolin, M-ficolin, and MASP-2 decreased, while MASP-3 increased after adjustment for baseline CRP. Baseline L-ficolin levels correlated positively with baseline ASDAS-CRP and BASFI. C3dg correlated positively with ASDAS-CRP. Conversely, MASP-1 and MAp44 correlated negatively with ASDAS-CRP. Assessed by univariate logistic regression, C3dg and MASP-1 were associated with treatment response of clinically important improvement (ΔASDAS-CRP ≥1.1) and inactive disease (ASDAS-CRP <1.3) at week 12, respectively. Only C3dg remained significant in a multivariate regression analysis. Conclusion: In this study, complement LPPs L-ficolin, M-ficolin, and MASP-2 levels decrease following initiation of TNFi therapy, whereas alternative pathway critical component MASP-3 increases. Baseline L-ficolin and C3dg correlated positively with ASDAS-CRP, potentially by CRP influence. Nevertheless, baseline C3dg levels were associated with treatment response (ASDAS-CRP <1.3) at week 12. Our results provide important perspectives on the inflammatory processes in axSpA, shedding light on the involvement of the complement system related to disease activity, treatment response, and potentially to prognosis.

Original language	English
Article number	rkaf007
Journal	Rheumatology advances in practice
Volume	9
Issue	1
Pages (from-to)	rkaf007
ISSN	2514-1775
DOIs	https://doi.org/10.1093/rap/rkaf007
Publication status	Published - Jan 2025

Keywords

axial spondyloarthritis
biomarker
complement activation
lectin pathway
tumour necrosis inhibitor therapy

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10.1093/rap/rkaf007

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Mistegaard, C., Troldborg, A., Torgutalp, M., Loft, A. G., Thiel, S., Muche, B., Rios Rodriguez, V., Protopopov, M., Listing, J., Sieper, J., Poddubnyy, D., & Proft, F. (2025). Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT. Rheumatology advances in practice, 9(1), rkaf007. Article rkaf007. https://doi.org/10.1093/rap/rkaf007

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title = "Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT",

abstract = "Objectives: To investigate lectin pathway proteins (LPPs) and complement activation marker C3dg as biomarkers for disease activity and treatment response in a multicentre, randomized controlled trial of axial spondyloarthritis (axSpA) patients initiating TNF inhibitor (TNFi) therapy. Methods: Serum samples from 108 patients with active radiographic axSpA from the CONSUL study, collected before and after 12 weeks of TNFi therapy, were measured using immunoassays for LPPs (MBL, CL-L1, M-, L-, and H-ficolin, MASP-1, -2, and -3, MAp44) and the complement activation marker C3dg. Results: After 12 weeks of TNFi therapy, serum levels of LPPs L-ficolin, M-ficolin, and MASP-2 decreased, while MASP-3 increased after adjustment for baseline CRP. Baseline L-ficolin levels correlated positively with baseline ASDAS-CRP and BASFI. C3dg correlated positively with ASDAS-CRP. Conversely, MASP-1 and MAp44 correlated negatively with ASDAS-CRP. Assessed by univariate logistic regression, C3dg and MASP-1 were associated with treatment response of clinically important improvement (ΔASDAS-CRP ≥1.1) and inactive disease (ASDAS-CRP <1.3) at week 12, respectively. Only C3dg remained significant in a multivariate regression analysis. Conclusion: In this study, complement LPPs L-ficolin, M-ficolin, and MASP-2 levels decrease following initiation of TNFi therapy, whereas alternative pathway critical component MASP-3 increases. Baseline L-ficolin and C3dg correlated positively with ASDAS-CRP, potentially by CRP influence. Nevertheless, baseline C3dg levels were associated with treatment response (ASDAS-CRP <1.3) at week 12. Our results provide important perspectives on the inflammatory processes in axSpA, shedding light on the involvement of the complement system related to disease activity, treatment response, and potentially to prognosis.",

keywords = "axial spondyloarthritis, biomarker, complement activation, lectin pathway, tumour necrosis inhibitor therapy",

author = "Clara Mistegaard and Anne Troldborg and Murat Torgutalp and Loft, {Anne Gitte} and Steffen Thiel and Burkhard Muche and {Rios Rodriguez}, Valeria and Mikhail Protopopov and Joachim Listing and Joachim Sieper and Denis Poddubnyy and Fabian Proft",

year = "2025",

month = jan,

doi = "10.1093/rap/rkaf007",

language = "English",

volume = "9",

pages = "rkaf007",

journal = "Rheumatology advances in practice",

issn = "2514-1775",

publisher = "Oxford University Press",

number = "1",

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Mistegaard, C , Troldborg, A, Torgutalp, M, Loft, AG , Thiel, S, Muche, B, Rios Rodriguez, V, Protopopov, M, Listing, J, Sieper, J, Poddubnyy, D & Proft, F 2025, 'Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT', Rheumatology advances in practice, vol. 9, no. 1, rkaf007, pp. rkaf007. https://doi.org/10.1093/rap/rkaf007

Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT. / Mistegaard, Clara ; Troldborg, Anne; Torgutalp, Murat et al.
In: Rheumatology advances in practice, Vol. 9, No. 1, rkaf007, 01.2025, p. rkaf007.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Complement proteins in axial spondyloarthritis

T2 - associations with disease activity and TNFi treatment response in a multicentre RCT

AU - Mistegaard, Clara

AU - Troldborg, Anne

AU - Torgutalp, Murat

AU - Loft, Anne Gitte

AU - Thiel, Steffen

AU - Muche, Burkhard

AU - Rios Rodriguez, Valeria

AU - Protopopov, Mikhail

AU - Listing, Joachim

AU - Sieper, Joachim

AU - Poddubnyy, Denis

AU - Proft, Fabian

PY - 2025/1

Y1 - 2025/1

N2 - Objectives: To investigate lectin pathway proteins (LPPs) and complement activation marker C3dg as biomarkers for disease activity and treatment response in a multicentre, randomized controlled trial of axial spondyloarthritis (axSpA) patients initiating TNF inhibitor (TNFi) therapy. Methods: Serum samples from 108 patients with active radiographic axSpA from the CONSUL study, collected before and after 12 weeks of TNFi therapy, were measured using immunoassays for LPPs (MBL, CL-L1, M-, L-, and H-ficolin, MASP-1, -2, and -3, MAp44) and the complement activation marker C3dg. Results: After 12 weeks of TNFi therapy, serum levels of LPPs L-ficolin, M-ficolin, and MASP-2 decreased, while MASP-3 increased after adjustment for baseline CRP. Baseline L-ficolin levels correlated positively with baseline ASDAS-CRP and BASFI. C3dg correlated positively with ASDAS-CRP. Conversely, MASP-1 and MAp44 correlated negatively with ASDAS-CRP. Assessed by univariate logistic regression, C3dg and MASP-1 were associated with treatment response of clinically important improvement (ΔASDAS-CRP ≥1.1) and inactive disease (ASDAS-CRP <1.3) at week 12, respectively. Only C3dg remained significant in a multivariate regression analysis. Conclusion: In this study, complement LPPs L-ficolin, M-ficolin, and MASP-2 levels decrease following initiation of TNFi therapy, whereas alternative pathway critical component MASP-3 increases. Baseline L-ficolin and C3dg correlated positively with ASDAS-CRP, potentially by CRP influence. Nevertheless, baseline C3dg levels were associated with treatment response (ASDAS-CRP <1.3) at week 12. Our results provide important perspectives on the inflammatory processes in axSpA, shedding light on the involvement of the complement system related to disease activity, treatment response, and potentially to prognosis.

AB - Objectives: To investigate lectin pathway proteins (LPPs) and complement activation marker C3dg as biomarkers for disease activity and treatment response in a multicentre, randomized controlled trial of axial spondyloarthritis (axSpA) patients initiating TNF inhibitor (TNFi) therapy. Methods: Serum samples from 108 patients with active radiographic axSpA from the CONSUL study, collected before and after 12 weeks of TNFi therapy, were measured using immunoassays for LPPs (MBL, CL-L1, M-, L-, and H-ficolin, MASP-1, -2, and -3, MAp44) and the complement activation marker C3dg. Results: After 12 weeks of TNFi therapy, serum levels of LPPs L-ficolin, M-ficolin, and MASP-2 decreased, while MASP-3 increased after adjustment for baseline CRP. Baseline L-ficolin levels correlated positively with baseline ASDAS-CRP and BASFI. C3dg correlated positively with ASDAS-CRP. Conversely, MASP-1 and MAp44 correlated negatively with ASDAS-CRP. Assessed by univariate logistic regression, C3dg and MASP-1 were associated with treatment response of clinically important improvement (ΔASDAS-CRP ≥1.1) and inactive disease (ASDAS-CRP <1.3) at week 12, respectively. Only C3dg remained significant in a multivariate regression analysis. Conclusion: In this study, complement LPPs L-ficolin, M-ficolin, and MASP-2 levels decrease following initiation of TNFi therapy, whereas alternative pathway critical component MASP-3 increases. Baseline L-ficolin and C3dg correlated positively with ASDAS-CRP, potentially by CRP influence. Nevertheless, baseline C3dg levels were associated with treatment response (ASDAS-CRP <1.3) at week 12. Our results provide important perspectives on the inflammatory processes in axSpA, shedding light on the involvement of the complement system related to disease activity, treatment response, and potentially to prognosis.

KW - axial spondyloarthritis

KW - biomarker

KW - complement activation

KW - lectin pathway

KW - tumour necrosis inhibitor therapy

UR - http://www.scopus.com/inward/record.url?scp=85217920530&partnerID=8YFLogxK

U2 - 10.1093/rap/rkaf007

DO - 10.1093/rap/rkaf007

M3 - Journal article

C2 - 39959130

SN - 2514-1775

VL - 9

SP - rkaf007

JO - Rheumatology advances in practice

JF - Rheumatology advances in practice

IS - 1

M1 - rkaf007

ER -

Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT

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