LRP4 Antibodies by CBA, Serum

Low Density Lipoprotein Receptor-Related Protein 4; LDLRP4; Myasthenia gravis (MG) autoantibodies

LRP4 Antibodies by CBA

Serum

Low density lipoprotein receptor-related protein 4 (LRP4) is a receptor protein on the neuromuscular junction that binds with the protein agrin and is critical for NMJ formation and maintenance via MuSK activation. Autoantibodies for LRP4 have been shown to be present and causal for MG in patients found to be double seronegative for AChR Ab and MuSK Ab.
Myasthenia gravis (MG) is an autoimmune disorder that leads to weakness and diminished control over voluntary muscles. It results from reduced signaling in the neuromuscular junction (NMJ) that connects nerves to muscle fibers. Typically, the areas of reduced functioning are the muscles of the eyes, face, and throat. There are three types of acquired MG: ocular (OMG), bulbar predominant (BMG), and generalized (GMG).
In MG, the body produces antibodies (Ab) that bind with receptors in the NMJ, blocking or destroying them, thereby preventing chemical signaling from the brain to the muscles.
The majority of cases (about 85%) of MG are caused by autoantibodies targeting the acetylcholine receptors (AChR). Approximately 6% of cases are caused by autoantibodies targeting the extracellular domain of muscle specific tyrosine-kinase (MuSK) receptors. Amongst the approximately 15% of cases of MG that are found to be AChR Ab-negative, however, MuSK Abs have been reported in patients with frequencies ranging from 0 – 64%, depending on ethnic group and geographic location.
The remaining cases are considered double-seronegative MG, as the patients sera appears negative for both AChR and MuSK antibodies. These cases can be caused by autoantibodies to a variety of other proteins, including but not limited to lipoprotein-related protein 4 (LRP4), agrin, and cortactin.