Screening for LRP4 autoantibodies is performed in patients with suspected myasthenia gravis (severe myasthenia).
The lipoprotein receptor-related protein-4 (LRP4) is a member of a family of membrane proteins with key roles in neuronal and synaptic development. LRP4 and specific muscle kinase (MuSK) form together with the acetylcholine receptor (AChR) complexes in neuromuscular synapse, and it is precisely in these complexes that membrane potential evolves in response to nerve stimulation. Antibodies against the LRP4 antigen have been found in patients with myasthenia gravis sero-negative for AChR and MuSK antibodies. The incidence of LRP4 antibodies was 19% in a large study of 635 patients, but with high variability between different populations (from 7 to 33%). Patients with positive antibodies against LRP4 respond to similar treatment to patients who are positive for acetylcholine receptor (AChR) antibodies, as opposed to patients with MuSK positive antibodies. There are also patients with myasthenia gravis who are double positive, i.e. having both anti-AChR and anti-LRP4 antibodies or simultaneous anti-MuSK and anti-LRP4 antibodies. Double positive patients generally have more severe symptoms.
See also: MuSK Antibodies, AChR Antibodies, LRP4 Antibodies