Chronic Inflammatory Demyelinating Polyneuropathy Research Articles

Prospective open-label trial with rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy not responding to conventional immune therapies

BackgroundTo evaluate the efficacy of rituximab in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients not responding to conventional immune therapies.MethodsAn open-label, prospective exploratory study was conducted with intravenous rituximab on 17...

Usefulness of somatosensory evoked potentials for monitoring the clinical course of patients with chronic inflammatory demyelinating polyradiculoneuropathy.

Somatosensory evoked potentials (SSEPs) are described as a supportive tool to diagnose chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); however, there is a lack of studies determining the effectiveness of SSEPs in monitoring the clinical course of individuals with this condition. The aims of this study are to evaluate the utility of SSEPs in monitoring patients with CIDP and to assess their association with clinical outcomes following immunomodulatory therapy. This was a single-center retrospective observational study that included patients who met European Federation of Neurological Societies and Peripheral Nerve Society criteria for CIDP between 2018 and 2023. SSEPs were performed at diagnosis and during follow-up after the start of immunomodulatory treatment. Fisher's exact test was employed to assess the association between clinical improvement and SSEP improvement. Eighteen patients were included in the study. Ten patients had a typical CIDP pattern and 11 were male. In 17, SSEPs were abnormal prior to the start of immunomodulatory treatment. In patients who showed clinical improvement with immunomodulatory therapy, we observed that 15/17 had partial or complete improvement in SSEPs. Patients who showed no clinical improvement with first-line treatment exhibited worsening SSEPs. There was a significant association between clinical and SSEPs improvement (p = 0.009). We observed a positive association between improvement in SSEPs and clinical improvement in patients with CIDP. Our data suggest that SSEPs may be useful for monitoring the clinical course of patients with CIDP, but additional, larger studies are needed.

Late diagnosis of chronic inflammatory demyelinating polyneuropathy on the background of misdiagnosed alcoholic polyneuropathy: a clinical case

Chronic inflammatory demyelinating polyneuropathy is a rare immune-mediated polyneuropathy pathology of the peripheral nervous system. The presence of etiological factors in the patient, such as type 1 and 2 diabetes mellitus, alcohol intoxication in the anamnesis or other causes of polyneuropathy, which are often found in practice, can disguise chronic inflammatory demyelinating polyneuropathy and lead to delayed diagnosis of potentially curable polyneuropathy, which further increases the likelihood of disability of the patient and a significant decrease in the quality of his life. The clinical case under consideration is a demonstration of such diagnostic difficulties, which led to a delayed diagnosis of chronic inflammatory demyelinating polyneuropathy against the background of alcohol abuse in the debut of neurological disorders.

Immunoglobulins: Mechanistic Approaches in Moderation of Various Inflammatory and Anti-Inflammatory Pathways.

Immunoglobulins (Ig) are proteins that help fight infections. IgG (IgG1, IgG2, IgG3, IgG4), IgM, IgA, IgD, and IgE are the five immunoglobulin subtypes that make up the majority of our immune system. Beneficial effects have been observed on the administration of Ig in diseases like Kawasaki, multiple myositis, chronic inflammatory demyelinating polyneuropathy (CIDP), and immune thrombocytopenia purpura (ITP). The Fc region, FcγRs, and FcRn of the IgG interact to provide both pro- and anti-inflammatory effects. IgM blocks immune-mediated inflammation using N-like glycans. It has been demonstrated that IgM demonstrates its antiinflammatory activity through IgM anti-leukocyte auto-antibodies (IgM-ALA). Since IgA is the second most prevalent and important Ig that operates on the primary objective in the immune system, which exhibits inhibitory signals in the body and generates inflammation in host cells, it plays a critical role in controlling mucosal homeostasis in the gastrointestinal (GI) tract. Additionally, it has been discovered that activating FcαRI boosts cytokine responses at different levels. IgD, a mysterious class of Ig once discovered, has a role in many disorders, including myeloma and Hodgkin's disease. The stability of IgD with development shows a different role, which has an advantage for the host's survival. IgE is mainly associated with many allergic diseases (food allergies), mediates type 1 responses, and has defenses against parasitic infections, which makes it an important parameter for monoclonal antibodies. Studies showed the possible roles of immunoglobulins, from which it came to light that immunoglobulins have their functions as agonists and antagonists in inflammation.

Proteomics analysis of immune response-related proteins in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

The objective is to characterize differentially expressed proteins (DEPs) in Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) through high-throughput analysis. Sera from 11 healthy controls (HCs), 21 GBS and 19 CIDP patients were subjected to Olink Proteomics Analysis. In the comparison between CIDP and GBS groups, up-regulation of ITM2A and down-regulation of NTF4 were observed. Comparing GBS with HCs revealed 18 up-regulated and 4 down-regulated proteins. Comparing CIDP with the HCs identified 15 up-regulated and 4 down-regulated proteins. Additionally, the correlation between clinical characteristics and DEPs were uncovered. In conclusion, the DEPs have significant potential to advance our understanding of the pathogenesis in these debilitating neurological disorders.

Chronic inflammatory demyelinating polyneuropathy following COVID-19 vaccination: a case report and literature review

BackgroundSevere post-vaccination neurological complications are rare. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an immune-mediated polyneuropathy affecting the peripheral nerve roots, which is not well described as a post-vaccination side effect. Here, we present a rare complication of vaccination against SARS-CoV-2, reaching a diagnosis of CIDP.Case presentationA 67-year-old diabetic male presented with lower extremity paresthesia and weakness following the third dose of the Sinopharm (BBIBP-CorV) vaccine. Despite initial dismissal as a diabetic complication, symptoms escalated, affecting all extremities. Electromyography study revealed abnormal spontaneous activity with chronic reinnervation changes, which was more significant in the lower extremities. Based on the clinical course, radiographic imaging, and laboratory data, a diagnosis of CIDP with severe axonal demyelinating features was established. Treatment with intravenous immunoglobulin (IVIg), prednisolone, and azathioprine resulted in marked improvement of the upper extremities but limited recovery in distal lower extremity muscles.ConclusionAlthough CIDP is a rare complication following COVID-19 vaccination, it should be considered in the differential diagnosis. Timely diagnosis of vaccine-induced CIDP is challenging, and any delay can adversely affect treatment response in affected patients.

Age-stratified mosaic of neuropathies: a comprehensive analysis of the prevalence and patterns in different age groups

Background and Objective: Neuropathies pose significant challenges in diagnosis and management due to their heterogeneous etiologies, varied clinical presentations, and differential prevalence across age groups. The objective of this study was to analyze the distribution of neuropathies among patients in various age brackets, highlighting prevalent neuropathic types and their clinical implications. Methods: From September 18, 2018 to September 17, 2019, 405 patients from Neurology Ward of Chandka Medical College Hospital in Larkana were included in this retrospective cross-sectional comprehensive analysis. Nerve conduction studies (NCS) of these patients were conducted in the electrophysiology department. The study cohort was stratified into age groups, allowing us to compare the frequency and NCS findings of various neuropathies. Statistical analysis using SPSS 23 was performed to ascertain the prevalence and distribution of specific neuropathies across different age brackets. Results: In the younger age group below 20 years, a prominent prevalence of neuropathies linked to hereditary factors was notable. Contrastingly, within the 20-40 age stratum, distinctive distribution patterns were observed, showcasing prevalent occurrences of Acute Inflammatory Demyelinating Polyneuropathy (AIDP) and those induced by trauma. Similarly, in the 40-60 and above 60 age cohorts, unique prevalence profiles emerged, spotlighting Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and neuropathies associated with diabetes and malignancies as most common. Conclusion: The findings of this study shed light on the age-related distribution of neuropathies and the corresponding NCS profiles. Such insights can aid in improving the diagnosis and management of neuropathies based on age, ensuring more tailored and effective healthcare strategies.

Treatment response amplitude and timing in chronic inflammatory demyelinating polyneuropathy with routine care: Study of a UK cohort.

The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care. We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new "CIDP treatment-response category" (CT-RC), based on achieved endpoints. Determinants of the CT-RC, of timing of maximum improvement, and of treatment discontinuation were ascertained. The CT-RC demonstrated high concurrent validity with current outcome measures. Thirty-six subjects (32.1%) achieved a "complete response," 37 (33%) a "good partial response," 10 (8.9%) a "moderate partial response," and 15 (13.4%) a "poor partial response." Fourteen subjects (12.5%) were "nonresponsive." The CT-RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1-36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders. CT-RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician- and patient-related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP.

Proteinuria is a key to suspect autoimmune nodopathies.

Reports of patients who have autoimmune nodopathies concurrent with nephrotic syndrome are increasing. We investigated whether proteinuria could be a biomarker of autoimmune nodopathies. Qualitative urinalysis results were retrospectively obtained from 69 patients who were diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) at a hospital in Japan. Proteinuria was graded as mild to severe (i.e., mild, 30-99; moderate, 100-299; severe, 300 mg/dL or more) according to the results of the urine dipstick test. Autoantibodies against the paranodal proteins contactin 1 (CNTN1), neurofascin 155 (NF155), and contactin-associated protein 1 (Caspr1) and the nodal protein neurofascin 186 (NF186) were measured, and the predominant IgG subclass was determined by enzyme-linked immunosorbent assay in sera from the 69 patients. Four patients (6%), five patients (7%), and one (1%) patient were positive for anti-CNTN1, anti-NF155, and anti-Caspr1 IgG4 antibodies, respectively. No patients had IgG4 antibodies against NF186. Proteinuria of mild or greater levels was found in three patients with anti-CNTN1 IgG4 and two patients with anti-NF155 IgG4 antibodies. The autoantibody-positive patients more frequently had proteinuria of mild or greater levels than the seronegative patients (p = 0.01). Proteinuria is a possible biomarker of autoimmune nodopathies associated with autoantibodies targeting CNTN1 or NF155. Urinalysis results should be carefully checked for quick differentiation of autoimmune nodopathies from CIDP. Patients who present with nephrotic syndrome should be tested for anti-CNTN1 IgG4 antibodies, and patients who exhibit mild proteinuria should be tested for anti-NF155 IgG4 antibodies.

Lingual Fasciculation as a Point of Call for the Diagnosis of Amyotrophic Lateral Sclerosis: A Literature Review.

Dental surgeons often play a pivotal role in the initial detection of lingual fasciculations (LFs). These involuntary micro-movements of the tongue can serve as early clinical indicators of neurodegenerative diseases, with amyotrophic lateral sclerosis (ALS) being the most concerning. Therefore, it is imperative to educate dental surgeons on identifying LF and understanding the potential underlying pathologies. This study aimed to pinpoint the pathologies in which LFs could emerge as an early clinical marker. Our review focused on articles delineating patient populations exhibiting LF within broader pathological contexts, encompassing neurological and other conditions, with the aim of elucidating their etiologies. We conducted a comprehensive literature review across four databases (PubMed, Embase, Web of Science, and Scopus). Two authors independently extracted data, with consultation from a third author when necessary. Eligible articles included those describing patients with LFs, detailing the methods of detection, diagnosis, and associated pathologies. Our review identified 22 articles encompassing 153 patients with LF, with an average age of 45.8 years and a female prevalence of 43%. Electromyography and ultrasound emerged as the predominant detection methods. ALS constituted the primary diagnosis in the majority of cases (91%). Additionally, other conditions diagnosed included Machado-Joseph disease (0.046%), familial transthyretin amyloid neuropathy (0.013%), Brown-Vialetto-Van-Laere syndrome (0.006%), chronic inflammatory demyelinating polyneuropathy (0.006%), bulbospinal amyotrophy or Kennedy's disease (0.006%), and osmotic demyelination syndrome (0.006%). LF secondary to organophosphate poisoning was also documented. Symptoms associated with LF encompassed taste alterations, dysphagia, difficulty swallowing, and slurred speech. While primarily indicative of ALS, LFs may also signal diverse underlying pathologies. Healthcare practitioners should be vigilant in their detection and expedite patient referrals to facilitate early integration into care protocols.

Treatment response in patients with clinical and supportive laboratory features of chronic inflammatory demyelinating polyneuropathy without demyelinative findings on nerve conduction studies: A retrospective study.

Not all patients with chronic inflammatory demyelinating polyneuropathy (CIDP) have evidence of demyelination on nerve conduction studies (NCS). Patients with "supportive" evidence of CIDP on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), ultrasound (US), or nerve biopsy but not on NCS, often receive immunomodulating therapy. We evaluated the treatment response of patients with clinical and supportive features of CIDP lacking NCS evidence of demyelination. Retrospective chart review was conducted on 232 patients who met CIDP clinical criteria and were treated with disease-modifying therapy. Patients included did not have NCS criteria of demyelination, but did have supportive CSF, MRI, or US findings consistent with CIDP. A positive treatment response was defined as at least a one-point improvement in the modified Rankin scale (mRS), or a four-point increase in the Medical Research Council sum score (MRCSS). Twenty patients met criteria: 17 of the 18 (94%) patients with CSF protein >45 mg/dL, 6 of the 14 (43%) with MRI lumbosacral root or plexus enhancement, and 4 of the 6 (67%) with enlarged proximal nerves on US. Eighteen patients received intravenous immunoglobulin, 10 corticosteroids, one plasma exchange, and six other immunomodulatory therapies. Twelve patients had a positive treatment response on the MRCSS or mRS. The presence of MRI lumbosacral root or plexus enhancement was associated with a positive treatment response. A trial of immunomodulating treatment should be considered for patients with clinical features of CIDP in the absence of NCS evidence of demyelination, particularly when there is MRI lumbosacral root or plexus enhancement.

Clinical and Electrophysiologic Findings of Fatigue in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Narrative Review

ABSTRACT Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nerve disease with progressive or recurrent motor and sensory symptoms lasting over 2 months. The condition is autoimmune and is diagnosed through clinical, electrodiagnostic, and laboratory features. This narrative review aims to summarize the latest findings on fatigue in CIDP, including its prevalence, factors that influence its severity, origin, and management strategies. Until May 20th, 2023, the English medical literature was searched with the keywords: “CIDP,” and “fatigue.” Study design, patient group, clinical findings related to CIDP and fatigue, treatment, and current status information were extracted from each study. One reviewer conducted research and screening, and another conducted the review process. Studies in English, including original studies and case series involving a minimum of five patients, were included until May 20th, 2023. Fatigue is a common symptom in CIDP, although not specific to the disease, and profoundly impacts the patient’s quality of life. The mechanisms specific to fatigue in CIDP are still unknown. However, we suggest that fatigue is not solely a residual symptom and may be related to inflammatory conditions. Further research is needed, specifically on the central origin of fatigue. It is essential to analyze the novel treatment options for fatigue in CIDP because it is a significant contributing factor to morbidity.

Autoimmune Nodopathy: When to Suspect and How to Treat?

Autoimmune nodopathy (AN) is a rare condition marked by autoantibodies that target specific proteins located within the node of Ranvier or paranodes. This disorder is distinctly different from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), with AN patients displaying unique clinical symptoms that include acute or subacute onset, primarily distal muscle weakness, sensory ataxia, tremors, and a significant increase in cerebrospinal fluid protein levels. Certain antibodies are linked to specific clinical manifestations; for instance, anti-contactin-1 neuropathy is often accompanied by nephrotic syndrome, whereas anti-pan-neurofascin neuropathy resembles fulminant Guillain-Barre syndrome. In contrast to CIDP patients, who usually experience substantial improvement with intravenous immunoglobulin (IVIG), those with AN may see poor or merely temporary benefits from IVIG therapy. Nonetheless, treatment with the anti-B cell therapy, rituximab, has shown promising results. These findings underscore the critical need for accurate identification of AN's clinical indicators, swift diagnosis of affected individuals, and the application of more effective, targeted treatments for this specific condition.

Autoimmune Nodopathy: When to Suspect and How to Treat?

Autoimmune nodopathy (AN) is a rare condition marked by autoantibodies that target specific proteins located within the node of Ranvier or paranodes. This disorder is distinctly different from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), with AN patients displaying unique clinical symptoms that include acute or subacute onset, primarily distal muscle weakness, sensory ataxia, tremors, and a significant increase in cerebrospinal fluid protein levels. Certain antibodies are linked to specific clinical manifestations; for instance, anti-contactin-1 neuropathy is often accompanied by nephrotic syndrome, whereas anti-pan-neurofascin neuropathy resembles fulminant Guillain-Barre syndrome. In contrast to CIDP patients, who usually experience substantial improvement with intravenous immunoglobulin (IVIG), those with AN may see poor or merely temporary benefits from IVIG therapy. Nonetheless, treatment with the anti-B cell therapy, rituximab, has shown promising results. These findings underscore the critical need for accurate identification of AN's clinical indicators, swift diagnosis of affected individuals, and the application of more effective, targeted treatments for this specific condition.

Central involvement in peripheral disease: melanopsin pathway impairment in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) compromises functions of the peripheral nervous system (PNS). Recently, however, symptoms such as cognitive deficits, visual dysfunction and circadian disorders were reported, compatible with additional involvement of the central nervous system (CNS) in CIDP. Against this background, we were interested in the functional state of melanopsin-expressing retinal ganglion cells (mRGCs) as a potential biomarker for sleep-wake abnormalities and CNS involvement in CIDP. Based on a chromatic pupillometry protocol, we examined the integrity of the melanopsin system in a prospective case-control study in 20 persons with CIDP compared to 20 controls without CIDP. The results were referred to clinical measures of disease severity and sleep behaviour. Patients with CIDP had a significantly reduced melanopsin-mediated post-illumination pupil response (PIPR) compared to healthy controls (25% versus 36%; P < 0.01). This reduction correlated with disease severity (r = 0.478, P < 0.05). Further, patients with CIDP reported diminished sleep quality (P < 0.05); however, there was no significant correlation with the melanopsin-mediated PIPR. The results demonstrate an impairment of mRGC function related to CIDP. Since the PIPR reduction correlated with disease severity, it could be an easily available biomarker for CNS affection in CIDP, a condition defined as PNS disorder.

Chronic inflammatory demyelinating polyneuropathy: current state of the problem (analysis of a clinical case)

Chronic inflammatory demyelinating polyneuropathy is an acquired autoimmune disease of the peripheral nervous system, heterogeneous in course and clinical manifestations, which is curable. The variety of forms of the disease and its course cause difficulties in timely diagnosis and initiation of pathogenetic therapy. This article presents a clinical observation of a patient with a wide range of concomitant pathologies, the presence of which significantly complicated the diagnosis and led to delayed prescription of immunosuppressive therapy.

Combined Central and Peripheral Demyelination (CCPD) Associated with MOG Antibodies: Report of Four New Cases and Narrative Review of the Literature

Background/Objectives: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. Methods: The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. Results: Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). Conclusions: The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.

EE500 Budget Impact of Subcutaneous Immunoglobulin, Intravenous Immunoglobulin, and Efgartigimod Alfa in Patients With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in the United States

EE500 Budget Impact of Subcutaneous Immunoglobulin, Intravenous Immunoglobulin, and Efgartigimod Alfa in Patients With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in the United States

New chronic inflammatory demyelinating polyneuropathy/Guillain-Barré syndrome guidelines - impact on clinical practise.

There is no diagnostic biomarker that can reliably detect Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnosis relies upon integrating key clinical characteristics and relevant supportive data. Consequently, misdiagnosis and delayed diagnosis are common. Diagnostic criteria have proven valuable resources to improve diagnosis, but are underutilized during routine clinical care. In 2021, the EAN/PNS CIDP criteria was published, and were followed by the EAN/PNS GBS criteria in 2023. Both guidelines utilized GRADE methodology to formulate evidence-based recommendations that are intended to be used by adult and paediatric clinicians across diverse care settings to optimize diagnostic accuracy and improve patient outcomes during routine clinical care. The EAN/PNS GBS and CIDP criteria detail specific clinical, electrophysiological, and laboratory features that raise diagnostic confidence, and call attention to diagnostic mimics. The sensitivity of EAN/PNS and other modern criteria to detect GBS and CIDP is high, but utilization during clinical practice is low. Complexity is one factor limiting widespread application. Strategies are needed to optimize criteria adoption during routine clinical care such that GBS and CIDP diagnosis can be achieved with greater speed and accuracy.

A pathologically expanded, clonal lineage of IL-21-producing CD4+ T cells drives inflammatory neuropathy.

Inflammatory neuropathies, which include chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain Barré syndrome (GBS), result from autoimmune destruction of the PNS and are characterized by progressive weakness and sensory loss. CD4+ T cells play a key role in the autoimmune destruction of the PNS. Yet, key properties of pathogenic CD4+ T cells remain incompletely understood. Here, we used paired single-cell RNA-Seq (scRNA-Seq) and single-cell T cell receptor-sequencing (scTCR-Seq) of peripheral nerves from an inflammatory neuropathy mouse model to identify IL-21-expressing CD4+ T cells that were clonally expanded and multifunctional. These IL-21-expressing CD4+ T cells consisted of 2 transcriptionally distinct expanded cell populations, which expressed genes associated with T follicular helper (Tfh) and T peripheral helper (Tph) cell subsets. Remarkably, TCR clonotypes were shared between these 2 IL-21-expressing cell populations, suggesting a common lineage differentiation pathway. Finally, we demonstrated that IL-21 receptor-KO (IL-21R-KO) mice were protected from neuropathy development and had decreased immune infiltration into peripheral nerves. IL-21 signaling upregulated CXCR6, a chemokine receptor that promotes CD4+ T cell localization in peripheral nerves. Together, these findings point to IL-21 signaling, Tfh/Tph differentiation, and CXCR6-mediated cellular localization as potential therapeutic targets in inflammatory neuropathies.