Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment

Clara Elbæk Mistegaard; Anne Troldborg; Annette Hansen; Steffen Thiel; Anne Grethe Jurik; Rosa M Kiil; Alice A Christiansen; Berit Schiøttz-Christensen; Oliver Hendricks; Susanne Juhl Pedersen; Inge Juul Sørensen; Mikkel Østergaard; Anne Gitte Loft

doi:10.3899/jrheum.2023-0164

Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment

Clara Elbæk Mistegaard, Anne Troldborg, Annette Hansen, Steffen Thiel, Anne Grethe Jurik, Rosa M Kiil, Alice A Christiansen, Berit Schiøttz-Christensen, Oliver Hendricks, Susanne Juhl Pedersen, Inge Juul Sørensen, Mikkel Østergaard, Anne Gitte Loft

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

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Abstract

OBJECTIVE: We have previously reported elevated levels of the complement lectin pathway proteins L-ficolin and H-ficolin in axial spondyloarthritis (axSpA) patients compared with healthy controls. The aim of this study was to investigate these biomarkers in a cross-sectional cohort of patients suffering from low back pain (LBP). Furthermore, we aimed to investigate changes in lectin pathway protein levels after initiation of adalimumab (TNF-inhibitor) in a longitudinal cohort of axSpA patients.

METHODS: Lectin pathway protein levels (mannan-binding lectin (MBL), collectin-L1 (CL-L1), H-ficolin, L-ficolin, M-ficolin, MBL-associated serine protease (MASP)-1 MASP-2, MASP-3, MBL-associated protein (MAp)19, and MAp44) were determined in EDTA plasma in two well-characterized cohorts; 1) a clinical cross-sectional cohort of patients with LBP, including axSpA patients (n=23), patients with unspecific LBP (uLPB) with ≥ 1 SpA feature(s) (n=55), and patients with uLBP without SpA features or MRI findings suggestive of axSpA (n=64), and 2) a randomized double-blinded placebo-controlled trial cohort of axSpA patients (n=49) initiating adalimumab therapy. Lectin pathway protein levels were determined using immunoassays.

RESULTS: Plasma levels of L-ficolin and M-ficolin were significantly increased in the cross-sectional cohort of newly diagnosed axSpA patients compared with clinically relevant controls with uLBP (all p<0.05). Both L-ficolin and M-ficolin decreased significantly after adalimumab therapy (p<0.05).

CONCLUSION: L-ficolin and M-ficolin levels are elevated in newly diagnosed axSpA patients compared with clinically relevant controls. Both L-ficolin and M-ficolin levels decrease significantly after initiating adalimumab therapy. These findings provide new insights into the inflammatory processes in axSpA and support a complement perspective in the axSpA pathogenesis.

Original language	English
Journal	The Journal of Rheumatology
Volume	51
Issue	1
Pages (from-to)	31-38
Number of pages	8
ISSN	0315-162X
DOIs	https://doi.org/10.3899/jrheum.2023-0164
Publication status	Published - Jan 2024

Keywords

axial spondyloarthritis
mannose-binding lectin complement pathway
tumor necrosis factor inhibitors

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10.3899/jrheum.2023-0164

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Mistegaard, C. E., Troldborg, A., Hansen, A., Thiel, S., Jurik, A. G., Kiil, R. M., Christiansen, A. A., Schiøttz-Christensen, B., Hendricks, O., Pedersen, S. J., Sørensen, I. J., Østergaard, M., & Loft, A. G. (2024). Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment. The Journal of Rheumatology, 51(1), 31-38. https://doi.org/10.3899/jrheum.2023-0164

@article{29e4dd946f6045c0bb8383f6e71dc7da,

title = "Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment",

abstract = "OBJECTIVE: We have previously reported elevated levels of the complement lectin pathway proteins L-ficolin and H-ficolin in axial spondyloarthritis (axSpA) patients compared with healthy controls. The aim of this study was to investigate these biomarkers in a cross-sectional cohort of patients suffering from low back pain (LBP). Furthermore, we aimed to investigate changes in lectin pathway protein levels after initiation of adalimumab (TNF-inhibitor) in a longitudinal cohort of axSpA patients.METHODS: Lectin pathway protein levels (mannan-binding lectin (MBL), collectin-L1 (CL-L1), H-ficolin, L-ficolin, M-ficolin, MBL-associated serine protease (MASP)-1 MASP-2, MASP-3, MBL-associated protein (MAp)19, and MAp44) were determined in EDTA plasma in two well-characterized cohorts; 1) a clinical cross-sectional cohort of patients with LBP, including axSpA patients (n=23), patients with unspecific LBP (uLPB) with ≥ 1 SpA feature(s) (n=55), and patients with uLBP without SpA features or MRI findings suggestive of axSpA (n=64), and 2) a randomized double-blinded placebo-controlled trial cohort of axSpA patients (n=49) initiating adalimumab therapy. Lectin pathway protein levels were determined using immunoassays.RESULTS: Plasma levels of L-ficolin and M-ficolin were significantly increased in the cross-sectional cohort of newly diagnosed axSpA patients compared with clinically relevant controls with uLBP (all p<0.05). Both L-ficolin and M-ficolin decreased significantly after adalimumab therapy (p<0.05).CONCLUSION: L-ficolin and M-ficolin levels are elevated in newly diagnosed axSpA patients compared with clinically relevant controls. Both L-ficolin and M-ficolin levels decrease significantly after initiating adalimumab therapy. These findings provide new insights into the inflammatory processes in axSpA and support a complement perspective in the axSpA pathogenesis.",

keywords = "axial spondyloarthritis, mannose-binding lectin complement pathway, tumor necrosis factor inhibitors",

author = "Mistegaard, {Clara Elb{\ae}k} and Anne Troldborg and Annette Hansen and Steffen Thiel and Jurik, {Anne Grethe} and Kiil, {Rosa M} and Christiansen, {Alice A} and Berit Schi{\o}ttz-Christensen and Oliver Hendricks and Pedersen, {Susanne Juhl} and S{\o}rensen, {Inge Juul} and Mikkel {\O}stergaard and Loft, {Anne Gitte}",

year = "2024",

month = jan,

doi = "10.3899/jrheum.2023-0164",

language = "English",

volume = "51",

pages = "31--38",

journal = "The Journal of Rheumatology",

issn = "0315-162X",

publisher = "Journal of Rheumatology",

number = "1",

}

Mistegaard, CE , Troldborg, A , Hansen, A , Thiel, S, Jurik, AG, Kiil, RM, Christiansen, AA, Schiøttz-Christensen, B, Hendricks, O, Pedersen, SJ, Sørensen, IJ, Østergaard, M & Loft, AG 2024, 'Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment', The Journal of Rheumatology, vol. 51, no. 1, pp. 31-38. https://doi.org/10.3899/jrheum.2023-0164

Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment. / Mistegaard, Clara Elbæk ; Troldborg, Anne ; Hansen, Annette et al.
In: The Journal of Rheumatology, Vol. 51, No. 1, 01.2024, p. 31-38.

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

TY - JOUR

T1 - Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment

AU - Mistegaard, Clara Elbæk

AU - Troldborg, Anne

AU - Hansen, Annette

AU - Thiel, Steffen

AU - Jurik, Anne Grethe

AU - Kiil, Rosa M

AU - Christiansen, Alice A

AU - Schiøttz-Christensen, Berit

AU - Hendricks, Oliver

AU - Pedersen, Susanne Juhl

AU - Sørensen, Inge Juul

AU - Østergaard, Mikkel

AU - Loft, Anne Gitte

PY - 2024/1

Y1 - 2024/1

N2 - OBJECTIVE: We have previously reported elevated levels of the complement lectin pathway proteins L-ficolin and H-ficolin in axial spondyloarthritis (axSpA) patients compared with healthy controls. The aim of this study was to investigate these biomarkers in a cross-sectional cohort of patients suffering from low back pain (LBP). Furthermore, we aimed to investigate changes in lectin pathway protein levels after initiation of adalimumab (TNF-inhibitor) in a longitudinal cohort of axSpA patients.METHODS: Lectin pathway protein levels (mannan-binding lectin (MBL), collectin-L1 (CL-L1), H-ficolin, L-ficolin, M-ficolin, MBL-associated serine protease (MASP)-1 MASP-2, MASP-3, MBL-associated protein (MAp)19, and MAp44) were determined in EDTA plasma in two well-characterized cohorts; 1) a clinical cross-sectional cohort of patients with LBP, including axSpA patients (n=23), patients with unspecific LBP (uLPB) with ≥ 1 SpA feature(s) (n=55), and patients with uLBP without SpA features or MRI findings suggestive of axSpA (n=64), and 2) a randomized double-blinded placebo-controlled trial cohort of axSpA patients (n=49) initiating adalimumab therapy. Lectin pathway protein levels were determined using immunoassays.RESULTS: Plasma levels of L-ficolin and M-ficolin were significantly increased in the cross-sectional cohort of newly diagnosed axSpA patients compared with clinically relevant controls with uLBP (all p<0.05). Both L-ficolin and M-ficolin decreased significantly after adalimumab therapy (p<0.05).CONCLUSION: L-ficolin and M-ficolin levels are elevated in newly diagnosed axSpA patients compared with clinically relevant controls. Both L-ficolin and M-ficolin levels decrease significantly after initiating adalimumab therapy. These findings provide new insights into the inflammatory processes in axSpA and support a complement perspective in the axSpA pathogenesis.

AB - OBJECTIVE: We have previously reported elevated levels of the complement lectin pathway proteins L-ficolin and H-ficolin in axial spondyloarthritis (axSpA) patients compared with healthy controls. The aim of this study was to investigate these biomarkers in a cross-sectional cohort of patients suffering from low back pain (LBP). Furthermore, we aimed to investigate changes in lectin pathway protein levels after initiation of adalimumab (TNF-inhibitor) in a longitudinal cohort of axSpA patients.METHODS: Lectin pathway protein levels (mannan-binding lectin (MBL), collectin-L1 (CL-L1), H-ficolin, L-ficolin, M-ficolin, MBL-associated serine protease (MASP)-1 MASP-2, MASP-3, MBL-associated protein (MAp)19, and MAp44) were determined in EDTA plasma in two well-characterized cohorts; 1) a clinical cross-sectional cohort of patients with LBP, including axSpA patients (n=23), patients with unspecific LBP (uLPB) with ≥ 1 SpA feature(s) (n=55), and patients with uLBP without SpA features or MRI findings suggestive of axSpA (n=64), and 2) a randomized double-blinded placebo-controlled trial cohort of axSpA patients (n=49) initiating adalimumab therapy. Lectin pathway protein levels were determined using immunoassays.RESULTS: Plasma levels of L-ficolin and M-ficolin were significantly increased in the cross-sectional cohort of newly diagnosed axSpA patients compared with clinically relevant controls with uLBP (all p<0.05). Both L-ficolin and M-ficolin decreased significantly after adalimumab therapy (p<0.05).CONCLUSION: L-ficolin and M-ficolin levels are elevated in newly diagnosed axSpA patients compared with clinically relevant controls. Both L-ficolin and M-ficolin levels decrease significantly after initiating adalimumab therapy. These findings provide new insights into the inflammatory processes in axSpA and support a complement perspective in the axSpA pathogenesis.

KW - axial spondyloarthritis

KW - mannose-binding lectin complement pathway

KW - tumor necrosis factor inhibitors

UR - http://www.scopus.com/inward/record.url?scp=85183418604&partnerID=8YFLogxK

U2 - 10.3899/jrheum.2023-0164

DO - 10.3899/jrheum.2023-0164

M3 - Journal article

C2 - 37714550

SN - 0315-162X

VL - 51

SP - 31

EP - 38

JO - The Journal of Rheumatology

JF - The Journal of Rheumatology

IS - 1

ER -

Complement Proteins L-Ficolin and M-Ficolin Are Increased in Patients With Axial Spondyloarthritis and Decrease After Tumor Necrosis Factor Inhibitor Treatment

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