559P Immunological biomarkers in immune-mediated and hereditary polyneuropathies

Proinflammatory cytokines, such as interleukin (IL)-8, IL6, and IL10, have been found to be higher in patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) compared to healthy controls. When comparing immunological pathway activation in patients with hereditary polyneuropathy (Charcot-Marie-Tooth (CMT)) and CIDP, similar levels of proinflammatory cytokines have been found. Furthermore, increased levels of components of the complement pathway in mouse models and CMT patients indicate inflammatory pathway activation in CMT. This suggests that inflammatory pathway activation is a driver for disease progression in CIDP as well as CMT, but larger studies are needed. The aim with our project is to investigate potential activation of immunologic pathways in a larger cohort of patients with CMT and CIDP. We include patients diagnosed with CIDP according to EAN/PNS diagnostic criteria and patients with genetically verified CMT followed at a specialized neuromuscular center. The study is a case-control study, with CIDP patients as disease controls. Patients are examined with evaluation of disease severity and blood biomarkers. Primary disease severity score is Inflammatory Neuropathy Cause and Treatment (INCAT), a validated outcome measure for disease severity in polyneuropathies. Secondary scores are 80-points Medical Research Council (MRC)-sum score, and handgrip strength, which are all validated outcome measures for disease severity in polyneuropathies. Plasma and serum will be collected according to protocol and frozen to -80 degrees Celsius, assuring stability of biomarkers when samples are frozen. The concentration of interleukins, TNF-alfa and complement factor will be analyzed using Multiplex assay in our laboratory. To test for differences in interleukin, TNF-alfa, and complement levels in CIDP patients compared to CMT patients, we will use two-sample t-test. Correlation between levels of interleukins and disease severity will be examined using Spearman correlation. A total of 144 patients have been included, 65 patients with CIDP and 79 patients with CMT. All patients have been examined with medical examination, physiotherapeutic tests, and blood samples and data are currently being analyzed. Blood samples are ready for analysis and results are expected in September 2024. Preliminary results will be presented at the conference. There is a vast need for understanding the variability of symptoms in polyneuropathies. Immunological activation may explain the clinical variability and could potentially lead to future “biomarker-guided” treatments.