Dataset Information

The Role of the Complement System in Chronic Inflammatory Demyelinating Polyneuropathy: Implications for Complement-Targeted Therapies.

ABSTRACT: Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common, heterogeneous, immune-mediated neuropathy, characterized by predominant demyelination of motor and sensory nerves. CIDP follows a relapsing-remitting or a progressive course and causes substantial disability. The pathogenesis of CIDP involves a complex interplay of multiple aberrant immune responses, creating a pro-inflammatory environment, subsequently inflicting damage on the myelin sheath. Though the exact triggers are unclear, diverse immune mechanisms encompassing cellular and humoral pathways are implicated. The complement system appears to play a role in promoting macrophage-mediated demyelination. Complement deposition in sural nerve biopsies, as well as signs of increased complement activation in serum and CSF of patients with CIDP, suggest complement involvement in CIDP pathogenesis. Here, we present a comprehensive overview of the preclinical and clinical evidence supporting the potential role of the complement system in CIDP. This understanding furnishes a strong rationale for targeting the complement system to develop new therapies that could serve the unmet needs of patients affected by CIDP, particularly in those refractory to standard therapies.

SUBMITTER: Querol LA

PROVIDER: S-EPMC9294101 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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The Role of the Complement System in Chronic Inflammatory Demyelinating Polyneuropathy: Implications for Complement-Targeted Therapies.

Querol Luis A LA Hartung Hans-Peter HP Lewis Richard A RA van Doorn Pieter A PA Hammond Timothy R TR Atassi Nazem N Alonso-Alonso Miguel M Dalakas Marinos C MC

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20220404 3

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common, heterogeneous, immune-mediated neuropathy, characterized by predominant demyelination of motor and sensory nerves. CIDP follows a relapsing-remitting or a progressive course and causes substantial disability. The pathogenesis of CIDP involves a complex interplay of multiple aberrant immune responses, creating a pro-inflammatory environment, subsequently inflicting damage on the myelin sheath. Though the exact triggers a ...[more]

PMID: 35378684

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Project description:Background and Objectives: Studies have suggested that, by applying certain nerve ultrasound scores, demyelinating and axonal polyneuropathies can be differentiated. In the current study, we investigated the utility of ultrasound pattern sub-score A (UPSA) and intra- and internerve cross-sectional area (CSA) variability in the diagnostic evaluation of demyelinating neuropathies. Materials and Methods: Nerve ultrasound was performed in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and acute inflammatory demyelinating polyneuropathy (AIDP) and compared to patients with axonal neuropathies. The UPSA, i.e., the sum of ultrasound scores at eight predefined measurement points in the median (forearm, elbow and mid-arm), ulnar (forearm and mid-arm), tibial (popliteal fossa and ankle) and fibular (lateral popliteal fossa) nerves, was applied. Intra- and internerve CSA variability were defined as maximal CSA/minimal CSA for each nerve and each subject, respectively. Results: A total of 34 CIDP, 15 AIDP and 16 axonal neuropathies (including eight axonal Guillain-Barré syndrome (GBS), four hereditary transthyretin amyloidosis, three diabetic polyneuropathy and one vasculitic neuropathy) were included. A total of 30 age- and sex-matched healthy controls were recruited for comparison. Significantly enlarged nerve CSA was observed in CIDP and AIDP with significantly higher UPSA in CIDP compared to the other groups (9.9 ± 2.9 vs. 5.9 ± 2.0 vs. 4.6 ± 1.9 in AIDP vs. axonal neuropathies, p < 0.001). A total of 89.3% of the patients with CIDP had an UPSA score ≥7 compared to the patients with AIDP (33.3%) and axonal neuropathies (25.0%) (p < 0.001). Using this cut-off, the performance of UPSA in differentiating CIDP from other neuropathies including AIDP was excellent (area under the curve of 0.943) with high sensitivity (89.3%), specificity (85.2%) and positive predictive value (73.5%). There were no significant differences in intra- and internerve CSA variability between the three groups. Conclusion: The UPSA ultrasound score was useful in distinguishing CIDP from other neuropathies compared to nerve CSA alone.

Project description:Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy that typically presents with progressive or relapsing, symmetric, proximal, and distal weakness of upper and lower limbs, sensory involvement of at least two limbs, and decreased or absent deep tendon reflexes. The symptoms of CIDP can be similar to those of other neuropathies, making diagnosis difficult, which can often lead to delays in correct diagnosis and treatment. The updated European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 guideline outlines a set of diagnostic criteria that help to identify CIDP with high accuracy and provides recommendations for the treatment of CIDP. The aim of this podcast, featuring Dr. Urvi Desai (Professor of Neurology, Wake Forest School of Medicine and Atrium Health Neurosciences Institute Wake Forest Baptist, Charlotte), is to discuss how the new guideline impacts diagnosis and treatment decisions in her everyday clinical practice. Using a patient case study example, the updated guideline recommends assessing a patient for clinical, electrophysiological, and supportive criteria for CIDP, enabling a more straightforward diagnosis of either typical CIDP, a CIDP variant, or an autoimmune nodopathy. A second patient case study highlights how the new guideline no longer considers autoimmune nodopathies as CIDP, as patients with these disorders do not meet hallmark CIDP criteria. This leaves an unmet need in terms of guidance on how to treat this subset of patients. Although the new guideline has not necessarily changed treatment preference in clinical practice, the addition of subcutaneous immunoglobulin (SCIG) into the guideline now better reflects clinical practice. The guideline helps to define and categorize CIDP more simply and consistently, allowing quicker and more accurate diagnosis, leading to a positive impact on treatment response and prognosis. These real-world insights into the diagnosis and management of patients with CIDP could help guide best clinical practice and help facilitate optimization of patient outcomes.

Dataset Information

The Role of the Complement System in Chronic Inflammatory Demyelinating Polyneuropathy: Implications for Complement-Targeted Therapies.

Publications

The Role of the Complement System in Chronic Inflammatory Demyelinating Polyneuropathy: Implications for Complement-Targeted Therapies.

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