Immune profiling of neurological diseases (IPoN)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous immune-mediated nerve disorder characterized by inflammation of nerve roots and peripheral nerves and demyelination of these nerves. With a prevalence of 0.7 to 10.3 cases per 100 000 people, it is considered a rare disease that shows considerable variation in clinical phenotype and disease progression among patients. Main treatment options for the disease include intravenous immunoglobulins, corticosteroids and plasma exchange, although therapy response may also vary among patients. This clinical heterogeneity observed within CIDP severely impacts its clinical management. For example, to diagnose CIDP, numerous diagnostic criteria have been published but problems still persist with respect to accurately and timely diagnosing the disease as both mis- and underdiagnosis of the disease has been reported. Blood-based biomarkers could significantly aid in diagnosing CIDP, but to date, no such biomarkers applicable to the broad population of patients with CIDP are available. Likewise, biomarkers to help establish an accurate prognosis or to monitor treatment response in this heterogeneous disease are urgently needed but are currently still lacking.

As biomarkers could significantly aid the clinical management of CIDP, research into blood-based CIDP biomarkers was a central theme in this PhD-project. The main objective was to explore peptides or peptide profiles derived from circulating immunoglobulin G (IgG) via mass spectrometry as novel diagnostic CIDP biomarkers. It was also investigated whether IgG-derived peptides could objectively clusters patients with CIDP and whether these clusters could be associated with specific clinical characteristics. As secondary objectives of the PhD-project, two other types of biomarkers that have been previously investigated in CIDP or other neurological diseases were further explored as possible CIDP biomarkers. First, I aimed to investigate the specificity of paranodal antibodies (PNAb) for CIDP-like phenotypes by measuring PNAb also in extended cohorts of patients with other neuromuscular disorders. A possible link between PNAb presence and Sjögren’s syndrome was hereby also explored. Secondly, the biomarker neurofilament light chain (NfL) was now investigated in CIDP as a potential prognostic biomarker with respect to disease progression and therapy response.