Immune-mediated neuropathies are a group of acquired disorders caused by an abnormal immune response attacking peripheral nerve structures, leading to demyelination and/or axonal damage (1). Their clinical manifestations are diverse, ranging from acutely onset, rapidly progressive quadriplegia to chronic, protracted symmetric weakness and sensory disturbances. Severe cases can be life-threatening due to respiratory muscle paralysis or result in long-term disability, placing a heavy burden on patients, families, and society (2). Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) are the most common and representative conditions within this disease spectrum.

GBS, as a typical acute inflammatory demyelinating polyradiculoneuropathy, has an annual incidence of approximately 0.8–1.9 per 100,000 and is one of the important causes of acute flaccid paralysis (3). CIDP, on the other hand, follows a chronic progressive or relapsing–remitting course, with a prevalence of about 0.8–8.9 per 100,000. If not diagnosed promptly and treated appropriately, it carries a very high disability rate (4). It is widely believed that the pathogenesis of immune-mediated neuropathies is not caused by a single factor, but rather results from a dysregulated immune system in genetically susceptible individuals, triggered by specific environmental factors, leading to cross-immune attacks on peripheral nerve components through mechanisms such as “molecular mimicry” (5, 6). Recent studies continue to support and refine this model, highlighting the complex interplay between host factors and environmental triggers (7).

Numerous studies have shown that preceding infections, particularly with Campylobacter jejuni, Cytomegalovirus (CMV), and Epstein–Barr virus (EBV), are the most important antecedent events and risk factors for GBS (8, 9). A systematic review from 2023 reaffirmed the strong association between C. jejuni infection and the axonal variant of GBS, particularly in East Asian populations (10). Additionally, vaccination, surgery, trauma, pregnancy, and comorbid autoimmune diseases are also considered potentially associated with disease initiation or relapse (8, 11). However, the incidence and risk factor profiles may vary across different regions and populations, and the interactions between these factors and their exact pathogenic mechanisms still require further elucidation (11).

Given the acute onset, severe condition, and variable prognosis of immune-mediated neuropathies, early identification of high-risk factors is crucial for disease warning, early diagnosis, and intervention (12). Currently, large-sample clinical epidemiological and multifactorial comprehensive analysis studies targeting this disease group are relatively limited in China. Therefore, this study aims to systematically investigate the clinical incidence and characteristics of immune-mediated neuropathies and thoroughly analyze their associated risk factors through a retrospective case–control analysis, to provide valuable clinical epidemiological evidence for identifying high-risk populations, formulating prevention strategies, and improving patient outcomes.

This study systematically explored the incidence and risk factors of immune-mediated neuropathies through a retrospective case–control analysis. Multivariate logistic regression analysis ultimately identified preceding Campylobacter jejuni infection, Cytomegalovirus infection, recent surgery/trauma history, and comorbid autoimmune diseases as four independent risk factors for the onset of immune-mediated neuropathies. These findings are consistent with most previous studies and further deepen our understanding of the pathogenesis of this disease. The aforementioned risk factors can be regarded as “triggering events” for the immune system, with the core mechanism being “molecular mimicry” (6, 14). That is, antigens from pathogens (such as lipooligosaccharides of Campylobacter jejuni, certain antigenic epitopes of CMV) or antigens released by damaged tissues share structural similarities with specific components of peripheral nerves (such as gangliosides GM1, GD1a, etc.). While the body produces high-titer antibodies and sensitized lymphocytes against these foreign antigens, it mistakenly attacks its own neural structures, triggering a cross-immune reaction, ultimately leading to demyelination, axonal damage, and even neuronal apoptosis, clinically manifesting as acute or chronic neurological deficits (2, 11). The result showing the highest risk for Campylobacter jejuni infection (OR = 4.52) in this study strongly supports its status as the most important trigger factor, a finding echoed in recent global surveillance data (15).

Regarding the incidence, the annual incidence rate found in this study (1.24 per 100,000) is similar to most reports domestically and internationally (3, 4). The predominance of male patients in the case group (60.1%) and the bimodal age distribution (20–30 years and 50–70 years) are noteworthy phenomena deserving further exploration. The higher incidence in males may be related to hormone levels, differences in immune response, and varying exposure opportunities to risk factors. The bimodal age distribution might reflect different susceptibility mechanisms: the younger peak may be associated with a more active immune system and greater exposure to infectious agents (16); while the older peak may be closely related to immune system dysfunction (17), increased comorbidities (18), and decreased neural repair capacity (19). A recent European study also reported a similar male predominance and discussed potential sex-based immunological differences underlying this disparity (20). Furthermore, this study again confirmed the key role of preceding infections, with a high percentage (70.9%) of patients having a clear history of infection before onset, predominantly respiratory and gastrointestinal infections, underscoring the importance of detailed inquiry about antecedent history in clinical practice.

The findings of this study have important clinical implications. First, they reinforce the awareness of identifying high-risk populations. For individuals who have recently experienced Campylobacter jejuni enteritis or CMV infection, undergone major surgery or severe trauma, or have other autoimmune diseases, clinicians should maintain a high index of suspicion for immune-mediated neuropathies if symptoms like limb weakness or numbness appear, striving for early diagnosis and intervention to improve outcomes. Second, at the public health level, emphasizing food safety to prevent Campylobacter jejuni infection has potential positive significance for reducing the incidence of GBS (21). Additionally, although vaccination was identified as a very low-risk trigger factor (OR = 3.25 in this study, but absolute risk is low), the results support enhanced monitoring of individual responses post-vaccination, while simultaneously emphasizing that the overall benefits of vaccination far outweigh its minimal risks, a balance that has been extensively reviewed in the context of large-scale vaccination campaigns (22).

Although several epidemiological studies on immune-mediated neuropathies have been conducted in China, most have focused on GBS alone or were limited by smaller sample sizes. Our study provides updated and comprehensive risk factor analysis based on a recent cohort (2020–2023), which may reflect current epidemiological trends and healthcare exposures. Furthermore, by including both GBS and CIDP within the spectrum of immune-mediated neuropathies, this study offers a broader perspective on shared and distinct risk factors, contributing to the growing body of regional data needed for tailored prevention and clinical vigilance.

Certainly, this study has several limitations. First, as a single-center retrospective study, there are inevitable selection and information biases. Second, the relatively limited sample size may affect the statistical power for certain rare risk factors (such as specific vaccine types). The etiological diagnosis of some preceding infections relied on serological testing, which may have false positives or negatives. Future larger-sample, multi-center prospective cohort studies are needed to further validate the conclusions of this study and to deeply explore the interactions between genetic susceptibility genes (such as HLA typing) and environmental risk factors, thereby providing a more solid theoretical basis for precise prevention and personalized treatment of the disease.