Autoimmune Aquaporin-4 Myopathy in Neuromyelitis Optica Spectrum (NMO)

nmo-featureA recent article in JAMA Neurology features a case report by a team of Mayo Clinic researchers of a 51-year-old woman with relapsing optic neuritis, transverse myelitis, aquaporin-4 (AQP4)-IgG seropositivity, and recurrent myalgias with hyperCKemia.

This case study, which documented muscle pathology compatible with targeting of sarcolemmal aquaporin-4 (AQP4) by complement-activating IgG, implies involvement of organs beyond the central nervous system in neuromyelitis optica spectrum (NMO) disorders.

The role of AQP4 in bioenergetic pathways and in the intracellular calcium dynamics of muscles suggests another potential mechanism for the hyperCKemia observed in NMO. Several muscle proteins related to metabolism are reduced in AQP4-null mice, without compromising sarcolemmal integrity. Calcium homeostasis is particularly perturbed in fast-twitch muscle fibers, which express AQP4 most abundantly. Thus, IgG-induced loss of sarcolemmal AQP4 in NMO could lead to metabolic and structural myofiber damage with resultant CK leakage.

In addition to skeletal muscle, it is predicted that the spectrum of NMO will extend to other AQP4-enriched organs, such as the kidney, heart, retina, inner ear, stomach, and bronchioles. Therapies targeting humoral immune responses can be anticipated to limit extra-CNS tissue injury in patients with NMO spectrum disorders as is observed for acute CNS manifestations.

Read the full article in JAMA Neurology.




Brent Westra is a Marketing Segment Manager at Mayo Clinic Laboratories. He leads marketing strategies for product management and specialty testing along with new media innovations. Brent has worked at Mayo Clinic since 2011.