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. 2021 Mar 23:14:1043-1053.
doi: 10.2147/JIR.S298307. eCollection 2021.

Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study

Anne-Lene Kjældgaard  1   2 , Katrine Pilely  1 , Karsten Skovgaard Olsen  2 , Anne Øberg Lauritsen  2 , Stephen Wørlich Pedersen  3 , Kirsten Svenstrup  3   4 , Merete Karlsborg  4 , Helle Thagesen  5 , Morten Blaabjerg  5 , Ásta Theódórsdóttir  6 , Elisabeth Gundtoft Elmo  3 , Anette Torvin Møller  7 , Niels Anker Pedersen  8 , Niels Kirkegaard  8 , Kirsten Møller  2   9 , Peter Garred  1   9
Affiliations

Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study

Anne-Lene Kjældgaard et al. J Inflamm Res. .

Abstract

Background: The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients.

Methods: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, -2, and -3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time.

Results: Compared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of complement markers and survival as estimated by hazard ratios.

Conclusion: ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiology of ALS.

Keywords: amyotrophic lateral sclerosis; cerebrospinal fluid; complement; innate immunity; lectin pathway; observational cohort study; pathophysiology.

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Conflict of interest statement

The authors report no conflicts of interest for this work.

Figures

Figure 1
Figure 1
Inclusion of patients.
Figure 2
Figure 2
Plasma or serum level of ficolin-2 (A), collectin-11 (B), C3bc (C), C4 (D), sC5b-9 (E), and C3bc/C3 (F) in samples from patients with ALS, NC, and NHC. The lower p-value of each figure describes that there is a significant difference in complement levels among the covariate groups. The remaining p-values describe whether there is a difference between the two, marked groups. *P-values = 0.01–0.05; **P-values = 0.01–0.001; ***P-values <0.0001.
Figure 3
Figure 3
CSF levels of ficolin-3 (A) and C3bc (C) in CSF in patients with ALS, NC and NHC. Values are mean (95% confidence interval). Correlation between plasma/serum levels and CSF levels of ficolin-3 (B) and C3bc (D) in ALS patients. *P-values = 0.01–0.05; **P-values = 0.01–0.001; ***P-values <0.0001.
Figure 4
Figure 4
Univariate regression analysis (Pearson’s correlation). The measured complement protein levels of collectin-11 (A), C3 (B), C3bc (C) were found to be significantly associated with ALSFRS-R.
See this image and copyright information in PMC

References

    1. Hardiman O, Al-Chalabi A, Brayne C, et al. The changing picture of amyotrophic lateral sclerosis: lessons from European registers. J Neurol Neurosurg Psychiatry. 2017;88(7):557–563. doi:10.1136/jnnp-2016-314495 - DOI - PubMed
    1. Kjældgaard AL, Pilely K, Olsen KS, et al. Amyotrophic lateral sclerosis: the complement and inflammatory hypothesis. Mol Immunol. 2018;102:14–25. doi:10.1016/j.molimm.2018.06.007 - DOI - PubMed
    1. Hawksworth OA, Coulthard LG, Woodruff TM. Complement in the fundamental processes of the cell. Mol Immunol. 2017;84:17–25. doi:10.1016/j.molimm.2016.11.010 - DOI - PubMed
    1. Magdalon J, Mansur F, Teles ESAL, de Goes VA, Reiner O, Sertié AL. Complement system in brain architecture and neurodevelopmental disorders. Front Neurosci. 2020;14:23. doi:10.3389/fnins.2020.00023 - DOI - PMC - PubMed
    1. Wang C, Yue H, Hu Z, et al. Microglia mediate forgetting via complement-dependent synaptic elimination. Science (New York, NY). 2020;367(6478):688–694. doi:10.1126/science.aaz2288 - DOI - PubMed