LRP4 Antibodies (Misc LAB000)

About 80-90% of patients with myasthenia gravis (MG) carry autoantibodies against the acetylcholine receptor (AChR). 20-38% of MG patients negative for AChR autoantibodies have muscle-specific receptor tyrosine kinase (MuSK) antibodies or convert to AChR autoantibodies within 12 months. Diagnosis of myasthenia gravis relies on the detection of these antibodies. Mayo Clinic’s Myasthenia Gravis Evaluation with MuSK reflex (LAB10008) is the preferred mechanism by which these antibodies can be tested. This panel starts by testing for anti-AChR, and will reflex to anti-MuSK if anti-AChR is undetected.

In rare cases of MG, both the AChR and MuSK antibodies are negative. 2-27% of these cases may have detectable anti-LRP4, particularly in ocular and generalized mild myasthenia gravis.

• A recent study conducted by the Mayo Clinic showed conflicting results suggesting false-positive LRP4 in 5-6% of all non-MG cases. These false-positive cases include non-MG confirmed cases based on normal clinical-electrodiagnostic testing (EDX) and healthy individuals.
• None of the EDX-confirmed seronegative MG cases were positive for LRP4 antibodies, showing the lack of utility of this assay. In addition, initial negative AChR and MuSK antibodies in patients with MG and confirmed with EDX presented a positive result in a repeat test in 10 out of 49 suspected MG cases.
• False positive LRP4 results can lead to inappropriate therapies for patients who lack clinical features and objective EDX evidence of MG. For this reason, LRP4 testing should be avoided for the diagnosis of MG.

• The Myasthenia Gravis Evaluation with MuSK reflex is the recommended diagnostic test for myasthenia gravis. This panel will test for AChR and if negative, it will reflex to MuSK.
• Despite some instances of LRP4 antibodies in patients negative for both AChR and MuSK, LRP4 testing is not recommended due to a high incidence of false positives, leading potentially to inappropriate therapies.

1. Shelly S, Paul P, Bi H, et al. Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm. Neurology. 2020;95(22):e3002-e3011. doi:10.1212/WNL.0000000000010910.
2. Klein CJ, Beecher G, Lamb C, et al. LRP4-IgG service line testing in seronegative myasthenia gravis and controls. J Neuroimmunol. 2022;368:577895. doi:10.1016/j.jneuroim.2022.577895.
3. Rivner MH, Quarles BM, Pan JX, et al. Clinical features of LRP4/agrin-antibody-positive myasthenia gravis: A multicenter study. Muscle Nerve. 2020;62(3):333-343. doi:10.1002/mus.26985.
4. Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14(10):1023-1036. doi:10.1016/S1474-4422(15)00145-3.