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LRP4 Antibodies

Lipoprotein receptor-related protein-4 (LRP4) is a member of a family of membrane proteins with key roles in neuronal and synaptic development. LRP4 protein activates MuSK kinase activity and promotes the clustering of AChR and their stabilization at the neuromuscular junction. Depolarization occurs in these clusters in response to nerve stimulation. Antibodies against LRP4 have been identified in myasthenia gravis patients who are seronegative for both AChR and MuSK antibodies. The frequency of LRP4 antibodies was 18.7% in a large international study (635 patients), but with a large variation between different populations (7 to 32.7%). The variation could not be linked to any geographic distribution. LRP4 antibody-positive patients respond to similar treatment strategy as AChR antibody positive patients, in contrast to MuSK antibody-positive patients. There are also double positive myasthenia gravis patients who are positive for antibodies against AChR and LRP4 or double positive against MuSK and LRP4. Double positive patients generally have more severe symptoms.

Method of detection at Euro Diagnostica Wieslab is indirect immunofluorescence (IIF) using cells transfected with LRP4. Results are reported as negative. Antibodies can be titrated. FDA has not approved this test has for diagnostic use in the United States.


Zouvelou V, Zisimopoulou P Rentzos M, Karandreas N, Evangelakou P Stamboulis E, Tzartos SJ Double seronegative myasthenia gravis with anti-LRP 4 antibodies. Neuromuscul Disord. 2013 Jul, 23 (7):568-70. PMID: 23768983

Zisimopoulou P. et al. A Comprehensive Analysis of the epidemiology and clinical characteristics of the anti-LRP4 in myasthenia gravis, Journal of Autoimmunity (2013), http://dx.doi.org/10.1016/j.jaut.2013.12.004 . PMID: 24373505

Berrih-Aknin S Frenkian-Cuvelier M, Eymard B. Diagnostic and Clinical Classification of autoimmune myasthenia gravis. J Autoimmun. 2014 Feb-Mar; 48-49:143-8. PMID: 24530233

Pevzner A, Schoser B, Peters K, Cosma NC, Karakatsani A, Schalke B, Melms A, Kröger S. Anti-LRP4 autoantibodies in AChR-and MuSK-antibody-negative myasthenia gravis. J Neurol. 2012 Mar; 259(3):427-35. PMID: 21814823

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Case #1 is an overview of transfusion reactions and a discussion of a neonate with both NAIT and Rh HDN.

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