Serum Neurofilament Light Chain as a Biomarker for CIDP Diagnosis, Severity, and Treatment Outcome

Abstract

Background and objectives: The aim of this study was to characterize serum neurofilament light chain (sNFL) levels in a large cohort of patients with autoimmune neuropathies to provide every-day clinical practice recommendations.

Methods: In this retrospective cohort study, we recruited 191 patients with immune-mediated neuropathies from 2 referral centers. sNFL was measured using the Simoa NF-light kit (Quanterix), and age-corrected and BMI-corrected z-scores (zNFL) were calculated. Clinical data were correlated with zNFL and adjusted for different disease subsets. A receiver operator characteristic analysis was performed. Treatments and longitudinal disease course of patients with typical chronic inflammatory demyelinating polyneuropathy (CIDP) in early disease stage were analyzed.

Results: One hundred ten patients had typical CIDP, and 67 had atypical CIDP. Fourteen patients had other immune neuropathies. zNFL of all patients correlated significantly with the Inflammatory Neuropathy Cause and Treatment Scale-overall disability sum score (r = 0.160), Medical Research Council Scale for Muscle Strength score (r = -0.242), modified Rankin Scale score (r = 0.151), and distal tibial compound muscle action potential (r = -0.151). The correlations remained only in the cohort of typical CIDP. zNFL >2 within the first 24 months of illness differentiated patients with atypical and typical CIDP with a sensitivity of 93%. Patients with early-stage typical CIDP with zNFL >2 (n = 9) presented with the most severe manifestation and did not respond to first-line (p < 0.0001) but to second-line treatments.

Discussion: We established sNFL as a promising biomarker for assessing disease activity in patients with typical CIDP. Elevated zNFL in early-stage typical CIDP indicate severe inflammatory-mediated axonal damage that requires aggressive immunotherapy.

Figure 1. sNFL [pg/ml] and sNFL z-Scores in CIDP Subsets and Other Autoimmune Neuropathies

(A) sNFL in all patients 26.63 ± 59.88, CIDP 24.07 ± 47.16, typical CIDP 28.75 ± 58.43, atypical CIDP 16.38 ± 14.01, DADS 15.48 ± 8.11, MADSAM 15.11 ± 8.7, other atypical CIDP 25.25 ± 37.24. (B) sNFL in MMN 15.34 ± 19.43, GBS 52.92 ± 56.18, paranodopathy 186.77 ± 316.13. (C) sNFL z-score in all patients 0.72 ± 1.51, CIDP 0.75 ± 1.45, typical CIDP 0.76 ± 1.6, atypical CIDP 0.75 ± 1.17, DADS 0.73 ± 1.18, MADSAM 0.7 ± 0.97. (D) sNFL z-score in MMN -0.11 ± 1.9, GBS 1.73 ± 2.51, paranodopathy 0.37 ± 3.32. Sample sizes: all n = 191, CIDP n = 177, typical CIDP n = 110, atypical CIDP n = 67, DADS n = 39, MADSAM n = 21, MMN n = 6, GBS n = 3, paranodopathy n = 3. CIDP = chronic inflammatory demyelinating polyneuropathy; DADS = distal acquired demyelinating symmetric polyneuropathy; GBS = Guillain-Barré syndrome; MADSAM = multifocal acquired demyelinating sensory and motor neuropathy; MMN = multifocal motor neuropathy.

Figure 2. Correlations of zNFL in Different Disease Subsets With Clinical Parameters

r Values and p values are provided in the figure. (A) zNFL correlation with INCAT-ODSS in patients with typical CIDP, n = 110. (B) zNFL correlation with INCAT-ODSS in patients with atypical CIDP, n = 67. (C) zNFL correlation with MRC-SS score in patients with typical CIDP, n = 110. (D) zNFL correlation with MRC-SS score in patients with atypical CIDP, n = 67. CIDP = chronic inflammatory demyelinating polyneuropathy; INCAT-ODSS = Inflammatory Neuropathy Cause and Treatment Scale–overall disability sum score; MRC-SS = Medical Research Council Scale for Muscle Strength.

Figure 3. Comparison of zNFL in Typical and Atypical CIDP Cohorts in Early (<24 Months) and Late (>24 Months) Disease Stages Since Manifestation

Typical CIDP <24 m (n = 27, zNFL = 1.6 ± 1.7); typical CIDP >24 m (n = 83, zNFL 0.5 ± 1.5); atypical CIDP <24 m (n = 14, zNFL = 0.4 ± 1.4); atypical CIDP >24 m (n = 53, zNFL = 0.9 ± 1.1); typical CIDP >24 m vs typical CIDP <24 m (p = 0.002); typical CIDP <24 m vs atypical CIDP <24 m (p = 0.028). CIDP = chronic inflammatory demyelinating polyneuropathy.

Figure 4. Longitudinal Clinical Observation of Patients With Typical CIDP With zNFL >2 and Early Disease Stage (<24 m) Individually (A and B) and Combined (C and D)

Significant disease amelioration of RODS sum score (B and D) after 2 years (56 ± 13; p = 0.023) and 3 years (63 ± 5; p = 0.026) in comparison with baseline (39 ± 16). n = 9. CIDP = chronic inflammatory demyelinating polyneuropathy; INCAT-ODSS = Inflammatory Neuropathy Cause and Treatment Scale–overall disability sum score; RODS = Rasch-built Overall Disability Scale.