TY - JOUR
T1 - Serum neurofilament light chain, contactin-1 and complement activation in anti-MAG IgM paraprotein-related peripheral neuropathy
AU - Amaador, Karima
AU - Wieske, Luuk
AU - Koel-Simmelink, Marleen J A
AU - Kamp, A
AU - Jongerius, Ilse
AU - de Heer, Koen
AU - Teunissen, Charlotte E
AU - Minnema, Monique C
AU - Notermans, Nicolette C
AU - Eftimov, Filip
AU - Kersten, Marie José
AU - Vos, Josephine M I
N1 - Funding Information:
Acknowledgments. This work was partially supported by the ANR (Agence Nationale de la Recherche), project Nosevol no ANR-11-BS01-0019 and by the Centre Henri Lebesgue (program “Investissements d’avenir” – no ANR-11-LABX-0020-01).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/7
Y1 - 2022/7
N2 - INTRODUCTION: In anti-myelin-associated glycoprotein IgM paraprotein-related peripheral neuropathy (anti-MAG PN), there is a lack of reliable biomarkers to select patients eligible for therapy and for evaluating treatment effects, both in routine practice and in clinical trials. Neurofilament light chain (NfL) and contactin-1 (CNTN1) can serve as markers of axonal and paranodal damage. Complement activation is involved in the pathogenesis in anti-MAG PN. We, therefore, hypothesized that serum NfL, CNTN1, C3b/c and C4b/c may function as biomarkers of disease activity in anti-MAG PN.METHODS: In this prospective cohort study, we included 24 treatment-naïve patients with anti-MAG PN (mean age 69 years, 57% male) that had IgM paraproteinemia, a high IgM MAG-antibody, and clinical diagnosis of anti-MAG PN by a neurologist specialized in peripheral nerve disorders. We measured serum NfL, CNTN1, C3b/c and C4b/c, reference values were based on healthy controls. As controls, 10 treatment-naïve patients with IgM Monoclonal gammopathy of undetermined significance (MGUS) or Waldenström's Macroglobulinemia (mean age 69 years, 60% male) without signs of neuropathy were included (non-PN).RESULTS: NfL, CNTN1 levels in serum were mostly normal in anti-MAG PN patients and comparable to non-PN patients. C3b/c and C4b/c levels were normal in anti-MAG PN patients.CONCLUSION: Our results do not support serum NfL, CNTN1, and C3b/c and C4b/c as potential biomarkers in anti-MAG PN, although we cannot exclude that subgroups or subtle abnormalities could be found in a much larger cohort with longitudinal follow-up.
AB - INTRODUCTION: In anti-myelin-associated glycoprotein IgM paraprotein-related peripheral neuropathy (anti-MAG PN), there is a lack of reliable biomarkers to select patients eligible for therapy and for evaluating treatment effects, both in routine practice and in clinical trials. Neurofilament light chain (NfL) and contactin-1 (CNTN1) can serve as markers of axonal and paranodal damage. Complement activation is involved in the pathogenesis in anti-MAG PN. We, therefore, hypothesized that serum NfL, CNTN1, C3b/c and C4b/c may function as biomarkers of disease activity in anti-MAG PN.METHODS: In this prospective cohort study, we included 24 treatment-naïve patients with anti-MAG PN (mean age 69 years, 57% male) that had IgM paraproteinemia, a high IgM MAG-antibody, and clinical diagnosis of anti-MAG PN by a neurologist specialized in peripheral nerve disorders. We measured serum NfL, CNTN1, C3b/c and C4b/c, reference values were based on healthy controls. As controls, 10 treatment-naïve patients with IgM Monoclonal gammopathy of undetermined significance (MGUS) or Waldenström's Macroglobulinemia (mean age 69 years, 60% male) without signs of neuropathy were included (non-PN).RESULTS: NfL, CNTN1 levels in serum were mostly normal in anti-MAG PN patients and comparable to non-PN patients. C3b/c and C4b/c levels were normal in anti-MAG PN patients.CONCLUSION: Our results do not support serum NfL, CNTN1, and C3b/c and C4b/c as potential biomarkers in anti-MAG PN, although we cannot exclude that subgroups or subtle abnormalities could be found in a much larger cohort with longitudinal follow-up.
KW - Anti-MAG neuropathy
KW - Biomarkers
KW - Demyelinating diseases
KW - IgM MGUS
KW - Peripheral neuropathy
KW - Waldenstrom Macroglobulinemia
UR - http://www.scopus.com/inward/record.url?scp=85124755974&partnerID=8YFLogxK
U2 - 10.1007/s00415-022-10993-4
DO - 10.1007/s00415-022-10993-4
M3 - Article
C2 - 35157138
SN - 0340-5354
VL - 269
SP - 3700
EP - 3705
JO - Journal of Neurology
JF - Journal of Neurology
IS - 7
ER -