Research Needs for Peripheral, Autonomic, & Central Nervous System Manifestations in Sjögren's Disease

For our 2026 research grant cycle, the Sjögren's Foundation will prioritize research focused on central, peripheral, and autonomic nervous system-related topics in Sjögren's. The Foundation hopes to stimulate interest in research in the neuro-immunological aspects of Sjögren's, which is vastly underresearched.

Examples of major research gaps for focus include prevalence of peripheral nervous system (PNS), central nervous system (CNS), and autonomic nervous system (ANS) manifestations, diagnosis and evaluation, therapy management, and outcome measures.

Here are examples of priority research questions to help guide you:

• What is the prevalence for PNS/ANS/CNS manifestations in Sjögren’s disease (SjD)?
• Is the scale used for interpreting skin punch biopsies when diagnosing small fiber neuropathies in diabetes applicable to SjD, or is a new or modified scale needed? 
• How can we develop improved scales to measure dynamic disabilities associated with ANS neuropathies that effectively capture the temporal variability of symptoms? 
• How can we standardize diagnostically accurate and minimally invasive testing methods, including imaging, biomarkers, and electrodiagnostic techniques, for PNS/ANS/CNS manifestations in SjD? 
• What is the sensitivity and specificity of lip biopsy in seronegative sicca-free patients with PNS and/or ANS dysfunction and personal and/or family history of autoimmune disease? 
• How can we develop diagnostic tools or scales to differentiate between progressive PNS/ANS/CNS manifestations and irreversible nerve damage? 
• What are the optimal first-line, second-line, and maintenance strategies (i.e. IVIG, other immunotherapies and pain management treatments) for PNS/ANS/CNS manifestations with varying degrees of symptom severity in SjD, and should treatment decisions be affected by autoantibody (anti-Sjögren’s syndrome A [SS-A], SS-B, rheumatoid factor [RF], antinuclear antibodies [ANA]) positivity? 
• How can we establish standardized and defined patient-centered outcomes for measuring PNS/ANS/CNS manifestations in SjD, considering their preferences in managing the benefits versus harms of treatment modalities? 
• What strategies can be developed to monitor response to therapy in SjD, including the potential utility of serial electrodiagnostic testing and patient-centered evaluations?   
• How can standardized outcome measures be used to evaluate treatment effectiveness for PNS/ANS/CNS manifestations in SjD?