Chronic inflammatory demyelinating polyneuropathy (CIDP) diagnoses are frequently missed or delayed and standard treatments — intravenous immunoglobulin (IVIG), steroids, and plasma exchange — are imperfect and less effective in some CIDP phenotypes.
Valid biomarkers could help both diagnosis and treatment, but CIDP has no widely accepted measures.
“Biomarkers can be challenging to understand in CIDP because of the rarity and heterogeneity of the disease,” said Jeffrey Allen, MD, of the University of Minnesota in Minneapolis. “They are desperately needed both to improve rapid and accurate diagnosis, and also to better understand disease activity.”
“Our ability to understand treatment effect — response or non-response — and disease activity status — remission versus ongoing immunologic activity — will become even more important as the CIDP treatment landscape evolves,” he added.
The Search for CIDP Markers
In 2021, Allen and co-authors outlined the decades-long search for CIDP biomarkers that included autoantibodies, cytokines, complement proteins, Fc receptor modulators and immunoglobulin G (IgG) levels, pathological markers, and electrophysiological and imaging measures.
Given CIDP’s heterogeneity, a set of biomarkers that describe nerve integrity and function, drug effects, and the activity of effector mechanisms may be needed, Allen and colleagues noted. Some biomarkers may be more useful in identifying disease subtypes, while others may be useful to monitor subclinical disease or treatment failure, they suggested.
“The pathophysiology of CIDP is not fully understood but likely involves diverse mechanisms between patients or perhaps even within individual patients at different stages of the disease,” they wrote.
Possible fluid biomarkers have included serum neurofilament light chain (NfL) which reflects axonal damage, the main predictor of poor outcome in CIDP. One study reported that levels of serum NfL were increased in a third of CIDP patients starting induction treatment, suggesting NfL may be a useful biomarker of disease activity in a subset of CIDP patients. A more recent study found that elevated serum NfL raised the odds for 1-year disease progression.
In CIDP patients with autoimmune nodopathies, anti-neurofascin-155 and anti-contactin-1 antibodies appeared to be biomarkers of relative resistance to IVIG therapy, which may help with therapeutic decisions and disease monitoring.
Other work has evaluated cerebrospinal fluid (CSF) sphingomyelin, the entire autoantigen repertoire, B-cell and T-cell receptor repertoire, and electrophysiologic studies, including the motor unit number index (MUNIX). CSF interleukin-8 (IL-8) levels distinguished people with Guillain-Barré syndrome from those with CIDP at the earliest stages of disease.
A genetic study also reported IVIG responsiveness changes in CIDP patients with variations in the PRF1 gene and the promoter region of FCGR2B.
“One ongoing project that aims to detect biomarkers is a study called INCbase,” Allen said.
“INCbase is an international CIDP registry and biobank with many objectives, one of which is to collect bio-samples from a large and diverse group of patients with CIDP for diagnostic and disease activity biomarker exploration,” he noted.
INCbase began enrollment in 2021, he added, and findings will be available as data from the study are analyzed.
Imaging Biomarkers
Biomarkers to help assess damage in CIDP include imaging. Long-standing interest in imaging peripheral nerves with MRI and ultrasound is reflected in the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) diagnostic guideline.
In 2024, researchers led by Hans Katzberg, MD, of the University of Toronto in Canada, evaluated whole-body magnetic resonance neurography (MRN) in CIDP, comparing patients and healthy controls using coronal 3-dimensional short tau inversion recovery (STIR) sampling with optimized contrasts to highlight nerve visibility.
“MRN offers the advantage of non-invasive, high-resolution imaging that can provide clear images of nerve continuity, integrity, and any pathological changes along the course of the nerve — capabilities that standard MRI or standard electrodiagnostic tests might not offer with the same precision,” Katzberg said.
The researchers found concordant symmetrical thickening and increased T2 signal in brachial and lumbosacral plexuses, femoral nerve, or sciatic nerve in five of eight CIDP patients, but in none of the healthy controls. A 4-month follow-up treatment effect study showed no treatment-related imaging changes in the five patients.
CIDP diagnoses are highly dependent on nerve conduction studies and electromyography, Katzberg observed, but those studies have limitations, “particularly in relation to their discomfort for the patient and their invasive nature,” he noted.
“Nerve conduction studies also may not adequately visualize the anatomical structures of nerves and surrounding tissues,” he observed. “This can be a critical gap in cases where detailed imaging could provide better diagnostic information or when a nerve’s physical state and its path through tissues need to be assessed comprehensively.”
Ultrasound imaging also has been extensively studied in CIDP. In 2024, researchers showed that ultra-high frequency ultrasound of nerve structures could distinguish immune neuropathies like CIDP from controls.
The EAN/PNS guideline suggests the use of ultrasound to diagnose CIDP in patients fulfilling diagnostic criteria for possible CIDP, noting that diagnosis may be more likely if there is nerve enlargement of at least two sites in proximal median nerve segments or the brachial plexus. The guideline has a similar suggestion for MRI to diagnose CIDP in adults who fulfill criteria for possible CIDP, adding that CIDP may be more likely with nerve root enlargement or increased signal intensity on MRI.
Disclosures
Allen reported relationships with Argenx, CSL Behring, Takeda, Grifols, and Alexion.
Katzberg reported no disclosures.
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