“Introduction
Autoantibodies to the lipoprotein receptor-related protein-4 (anti-LRP4) have been reported in a minority of patients with Myasthenia Gravis (MG), with potential pathogenic role and uncertain clinical relevance. However, LRP4 antibodies frequency varies substantially according to the type of assay used for their detection. Our aim is to investigate the prevalence of anti-LRP4 in a consecutive cohort of patients with suspected MG.

Methods
We established a live-CBA expressing full lenght LRP4, and used it to test a consecutive cohort of 333 patients with suspected MG. All samples were tested in parallel with validated ACHR and MUSK live-CBA. Seronegative MG (SNMG) diagnosis was assessed through clinical history, signs plus one among electromyography and cholinesterase response.

Results
The LRP4 CBA was validated by demonstrating its surface expression by staining of the live cells with a commercial antibody targeting extracellular epitopes of LRP4. Of the samples tested, 32% (n=108) were positive for either anti-AChR or anti-MuSK, while 0 were positive for LRP4. Among 225 triple-negative patients, a diagnosis of SNMG was established in 11% (n=26). The median age of SNMG patients at sampling was 63 years (range: 32-80), and 46% (n=12) were female. Thirty percent (n=8) of SNMG patients were collected at disease onset, and 58%(n=15) had GMG.

Discussion
LRP4 antibodies seem to be exceedingly rare, thus questioning their clinical relevance in routine clinical practice. As technical variations of the assays used for their detection have been reported, standardization studies are warranted to understand the actual clinical impact of requesting LRP4 testing.”