— Ongoing Quest for Reliable CIDP Biomarkers

Accurate diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) is often delayed or missed entirely, with standard options like intravenous immunoglobulin (IVIG), steroids, and plasma exchange offering inconsistent success, especially for certain CIDP subtypes.

Although promising, validated biomarkers remain elusive, which could potentially revolutionize both diagnosis and therapy for this complex condition.

"Biomarkers can be difficult to interpret in rare and heterogeneous diseases like CIDP," explained Jeffrey Allen, MD, from the University of Minnesota, Minneapolis. "Yet, they are sorely needed to enhance timely, precise diagnosis and to gain a firmer understanding of disease processes."

"As treatments for CIDP advance, our ability to quantify treatment response and disease activity — especially when distinguishing remission from ongoing immune activity — becomes ever more critical," added Allen.

The Push for CIDP Biomarkers

In a 2021 review, Allen and his team chronicled the extensive search for useful CIDP biomarkers over the years. Their research highlighted factors like autoantibodies, cytokine levels, complement proteins, IgG levels, and electrophysiological as well as imaging methods.

Considering CIDP's broad spectrum of presentations, the researchers proposed that a collection of biomarkers may be necessary to comprehensively describe nerve health, therapeutic impacts, and immune activation status. Some markers could assist in identifying specific disease subtypes, while others might be better suited for monitoring subclinical progression or treatment inefficacy.

"CIDP’s underlying mechanisms are complex and not fully understood. This may reflect different pathogenic drivers between patients, or even within the same patient depending on their disease stage," the team noted.

One promising fluid biomarker is serum neurofilament light chain (NfL), a key indicator of axonal damage and a major predictor of poor outcomes in CIDP. In one study, higher NfL levels were found in a third of patients beginning induction therapy, suggesting its potential as a biomarker for a subset of individuals with active disease. In a later study, elevated NfL was associated with a higher likelihood of disease progression over one year.

In autoimmune nodopathy-related CIDP patients, the presence of anti-neurofascin-155 and anti-contactin-1 antibodies could indicate relative resistance to IVIG treatment, serving as a guide for therapeutic decision-making.

Other research has explored various indicators, such as cerebrospinal fluid (CSF) markers, the immune cell repertoire, and electrophysiological measures like the motor unit number index (MUNIX). In early disease stages, raised CSF interleukin-8 (IL-8) levels helped differentiate Guillain-Barré syndrome from CIDP.

A genetic study also revealed that variations in the PRF1 gene and FCGR2B promoter region could influence IVIG response in patients.

Allen highlighted an ongoing project known as “INCbase.”

"INCbase is an international CIDP biobank and patient registry," he noted, "One of its goals is to gather biomaterials from a broad cohort of CIDP patients to aid in the discovery of diagnostic and disease activity biomarkers."

Since its 2021 initiation, INCbase continues to analyze patient data, and results will be reported in due course, Allen added.

Imaging as Biomarkers

Increasing attention is being paid to imaging methods that could potentially assess nerve damage in CIDP. The usefulness of imaging, including MRI and ultrasound techniques, is reflected in the diagnostic guidelines issued by the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS).

In 2024, a study led by Hans Katzberg, MD, from the University of Toronto, employed whole-body magnetic resonance neurography (MRN) to distinguish CIDP patients from healthy individuals. The research used coronal 3D short tau inversion recovery (STIR) methods, which improved nerve visibility.

"MRN offers detailed, non-invasive, high-resolution imaging of nerve continuity and pathological changes, which standard MRI or electrodiagnostic techniques might not capture as effectively," Katzberg stated.

The study identified symmetrical thickening and elevated T2 signals in nerves such as the brachial and lumbosacral plexuses, femoral, or sciatic nerves in five out of eight CIDP patients, compared to none in the healthy cohort. However, a follow-up study over four months revealed no imaging changes related to treatment in these patients.

While nerve conduction studies and electromyography are instrumental in CIDP diagnosis, Katzberg acknowledged their limitations, particularly their invasive nature and discomfort for patients.

"These tests often fail to provide a clear view of anatomical structures, potentially missing critical diagnostic insights where nerve or surrounding tissue states need thorough evaluation," he noted.

Ultrasound, too, has been heavily explored in diagnosing CIDP. By 2024, researchers demonstrated that ultra-high frequency ultrasound could accurately differentiate immune neuropathies like CIDP from healthy controls.

The EAN/PNS guidelines recommend using ultrasound for diagnosing CIDP in certain patients, specifically those who match preliminary CIDP criteria. Diagnosis becomes more plausible when nerve swelling is detected in two or more sites, such as the median nerve's proximal segments or the brachial plexus. MRI is suggested similarly, where root enlargement or increased signal intensity may support a CIDP diagnosis.

Disclosures

Dr. Allen reported affiliations with Argenx, CSL Behring, Takeda, Grifols, and Alexion.

Dr. Katzberg disclosed no relevant conflicts of interest.