Screening for autoantibody targets in post-vaccination narcolepsy using proteome arrays

Area of Science:

• Neuroimmunology
• Autoimmunity
• Vaccine safety

Background:

• Narcolepsy type 1 (NT1) is a rare autoimmune sleep disorder linked to hypocretin neuron loss.
• An increase in NT1 incidence was observed in Nordic countries post-Pandemrix® vaccination, suggesting a potential environmental trigger.
• The exact autoimmune targets (autoantigens) in NT1, particularly post-vaccination, remain elusive.

Purpose of the Study:

• To identify novel autoantigens associated with narcolepsy type 1 (NT1) in individuals vaccinated with Pandemrix®.
• To validate previously proposed autoantigens for NT1 using independent assays.

Main Methods:

• A two-step approach involving protein array screening of patient sera against over 9000 human proteins.
• Validation of candidate autoantigens using radiobinding assays (RBA) in a cohort of NT1 patients, relatives, and controls.

Main Results:

• Reactivity against previously suggested NT1 autoantigens was not replicated.
• Three novel candidate autoantigens (LOC401464, PARP3, FAM63B) were identified via protein array screening.
• Independent validation assays (RBA) failed to confirm elevated autoantibody reactivity against these novel candidates.

Conclusions:

• Protein array screening identified three potential autoantigens in Pandemrix®-associated NT1.
• The identified autoantibody targets could not be independently verified, suggesting they are not the primary drivers.
• Further research is essential to elucidate the specific autoantigens involved in the pathogenesis of Pandemrix®-induced NT1.