Modulation of the Soluble PD 1 Axis by Different Therapeutic Modalities in Chronic Inflammatory Demyelinating Polyneuropathy

Project summary

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disease, in which the immune system mistakenly attacks peripheral nerves. This can lead to progressive muscle weakness, sensory loss, numbness or pain and difficulties with walking. Under normal conditions, the immune system is kept in balance by “self-tolerance” mechanisms that prevent immune cells from attacking the body's own tissue. In CIDP, self-tolerance towards the peripheral nerves breaks down, resulting in ongoing immune-driven nerve damage. Importantly, this loss of tolerance might not be a one-time event. Breakdowns and attempts to regain self-tolerance can fluctuate over time, suggesting that the immune system is constantly trying, but failing, to restore control. Such dynamic is of clinical importance, as it may provide a window to assess autoimmune activity. 

Our discovery work identified the PD1-axis and the broader interconnected immune-checkpoint network as important modulator of peripheral nervous system self-tolerance. Generally, immune-checkpoints (ICs) act like molecular switches, that determine whether immune cells become activated or are turned off. We found that lower levels of soluble forms of these immune-checkpoint molecules, which can be measured in blood, were linked to more severe disease in CIDP. Furthermore, the immune-checkpoint network pattern was distinct in CIDP patients that stayed stable vs. patients that worsened within one year. 

This project builds on these findings, aiming now to understand how treatment influences the PD1-axis and the broader immune-checkpoint network dynamics and cooperation with other regulatory systems. We will investigate how different treatment modalities, first-line treatments (intravenous immunoglobulins and corticosteroids) and second-line therapies affect the PD1-axis and the broader immune-checkpoint network. We also aim to determine whether these blood-based checkpoint patterns can predict treatment response, potentially helping to identify which patients will respond to first-line therapy and which may require therapy escalation. A complementary mechanistical focus is to understand how intravenous immunoglobulins modifies immune-checkpoint activity patterns and dynamics across major immune-cell subtypes.  This aims to provide new insights into IVIg mechanisms of action and whether its effects on ICs across immune cell types explain variability in treatment response. 

Brief biosketch

Dr. Melissa Sgodzai is a biologist and, since 2026, a junior research group leader of the research group for Autoimmune Diseases of the Peripheral Nervous System under the mentorship of Prof. Ralf Gold and Prof. Kalliopi Pitarokoili at the Department of Neurology, Neuroimmunological Laboratory, St. Josef-Hospital, Ruhr University Bochum. She obtained her PhD in Neuroscience, summa cum laude, in December 2024 at the International Graduate School of Neuroscience at Ruhr University Bochum, where she conducted her research within the Institute of Prof. Ralf Gold and the research group of Prof. Kalliopi Pitarokoili. To date, she has accumulated 10 years of experience in mechanistic and translational research in autoimmune neuropathies.

During her doctoral training, she developed her independent research profile by establishing a framework to mechanistically dissect principles of peripheral nervous system self-tolerance and operationalize them into a clinically relevant context for autoimmune neuropathy. Based on this approach, her work positioned the PD1-axis and the broader immune checkpoint network as a new perspective on immunopathogenesis and translational biomarker research in chronic inflammatory demyelinating polyneuropathy (CIDP), as reported in Brain (2026). Her junior research group now continues to build on this framework and focuses on the mechanistic role of the PD1-axis and the broader immune checkpoint network, including LAG-3, TIM-3, and CTLA-4, in modulating peripheral nervous system self-tolerance and on translating these insights into biomarker development for disease trajectory prediction and therapy response in a bidirectional translational approach.

As part of her scientific development during her PhD training, one important milestone was a six-month research stay in the laboratory of Prof. Vijay Kuchroo at the Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women´s Hospital, supported by the Ruhr-University Research School and funded by Germany’s Excellence Initiative [DFG GSC 98/3] and the Brigham and Women’s Hospital Neurology Training Program. Furthermore, she is a founding member of the German Neuritis-Network, a multicentric patient-organization for autoimmune neuropathies.