Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000220126> ?p ?o ?g. }
- W2000220126 endingPage "5202" @default.
- W2000220126 startingPage "5190" @default.
- W2000220126 abstract "Myasthenia gravis (MG) is the most common disorder affecting the neuromuscular junction (NMJ). MG is frequently caused by autoantibodies against acetylcholine receptor (AChR) and a kinase critical for NMJ formation, MuSK; however, a proportion of MG patients are double-negative for anti-AChR and anti-MuSK antibodies. Recent studies in these subjects have identified autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), an agrin receptor also critical for NMJ formation. LRP4 autoantibodies have not previously been implicated in MG pathogenesis. Here we demonstrate that mice immunized with the extracellular domain of LRP4 generated anti-LRP4 antibodies and exhibited MG-associated symptoms, including muscle weakness, reduced compound muscle action potentials (CMAPs), and compromised neuromuscular transmission. Additionally, fragmented and distorted NMJs were evident at both the light microscopic and electron microscopic levels. We found that anti-LRP4 sera decreased cell surface LRP4 levels, inhibited agrin-induced MuSK activation and AChR clustering, and activated complements, revealing potential pathophysiological mechanisms. To further confirm the pathogenicity of LRP4 antibodies, we transferred IgGs purified from LRP4-immunized rabbits into naive mice and found that they exhibited MG-like symptoms, including reduced CMAP and impaired neuromuscular transmission. Together, these data demonstrate that LRP4 autoantibodies induce MG and that LRP4 contributes to NMJ maintenance in adulthood." @default.
- W2000220126 created "2016-06-24" @default.
- W2000220126 creator A5004772700 @default.
- W2000220126 creator A5004998023 @default.
- W2000220126 creator A5006231936 @default.
- W2000220126 creator A5023650604 @default.
- W2000220126 creator A5037736308 @default.
- W2000220126 creator A5041124719 @default.
- W2000220126 creator A5065643695 @default.
- W2000220126 creator A5067796695 @default.
- W2000220126 creator A5079899266 @default.
- W2000220126 creator A5082296195 @default.
- W2000220126 creator A5088490297 @default.
- W2000220126 date "2013-11-08" @default.
- W2000220126 modified "2023-10-17" @default.
- W2000220126 title "Antibodies against low-density lipoprotein receptor–related protein 4 induce myasthenia gravis" @default.
- W2000220126 cites W1524071937 @default.
- W2000220126 cites W1540450162 @default.
- W2000220126 cites W1561460904 @default.
- W2000220126 cites W1568142966 @default.
- W2000220126 cites W1963748908 @default.
- W2000220126 cites W1965076940 @default.
- W2000220126 cites W1967865726 @default.
- W2000220126 cites W1971032421 @default.
- W2000220126 cites W1971596565 @default.
- W2000220126 cites W1977454658 @default.
- W2000220126 cites W1980120506 @default.
- W2000220126 cites W1980294445 @default.
- W2000220126 cites W1984522719 @default.
- W2000220126 cites W1990099133 @default.
- W2000220126 cites W1990648371 @default.
- W2000220126 cites W1991623532 @default.
- W2000220126 cites W1993663077 @default.
- W2000220126 cites W1994793581 @default.
- W2000220126 cites W1997154375 @default.
- W2000220126 cites W2001765460 @default.
- W2000220126 cites W2004023547 @default.
- W2000220126 cites W2004818856 @default.
- W2000220126 cites W2007294766 @default.
- W2000220126 cites W2013292781 @default.
- W2000220126 cites W2014484514 @default.
- W2000220126 cites W2018252071 @default.
- W2000220126 cites W2026370029 @default.
- W2000220126 cites W2028203136 @default.
- W2000220126 cites W2035994978 @default.
- W2000220126 cites W2038591428 @default.
- W2000220126 cites W2043459401 @default.
- W2000220126 cites W2044625734 @default.
- W2000220126 cites W2045388885 @default.
- W2000220126 cites W2045434155 @default.
- W2000220126 cites W2046678465 @default.
- W2000220126 cites W2057502000 @default.
- W2000220126 cites W2058879345 @default.
- W2000220126 cites W2058892489 @default.
- W2000220126 cites W2063281798 @default.
- W2000220126 cites W2065078103 @default.
- W2000220126 cites W2067922514 @default.
- W2000220126 cites W2069700888 @default.
- W2000220126 cites W2072475795 @default.
- W2000220126 cites W2074062157 @default.
- W2000220126 cites W2082782477 @default.
- W2000220126 cites W2084486807 @default.
- W2000220126 cites W2086874557 @default.
- W2000220126 cites W2087265319 @default.
- W2000220126 cites W2091271011 @default.
- W2000220126 cites W2092874953 @default.
- W2000220126 cites W2094697595 @default.
- W2000220126 cites W2102175769 @default.
- W2000220126 cites W2102593255 @default.
- W2000220126 cites W2107024251 @default.
- W2000220126 cites W2108512667 @default.
- W2000220126 cites W2111821994 @default.
- W2000220126 cites W2114553342 @default.
- W2000220126 cites W2115423672 @default.
- W2000220126 cites W2118177888 @default.
- W2000220126 cites W2120700221 @default.
- W2000220126 cites W2120953264 @default.
- W2000220126 cites W2123125411 @default.
- W2000220126 cites W2142190605 @default.
- W2000220126 cites W2144696840 @default.
- W2000220126 cites W2144864783 @default.
- W2000220126 cites W2146251481 @default.
- W2000220126 cites W2146831407 @default.
- W2000220126 cites W2148646540 @default.
- W2000220126 cites W2154944042 @default.
- W2000220126 cites W2158208349 @default.
- W2000220126 cites W2164681071 @default.
- W2000220126 cites W2170822425 @default.
- W2000220126 cites W4295682875 @default.
- W2000220126 cites W68353136 @default.
- W2000220126 doi "https://doi.org/10.1172/jci66039" @default.
- W2000220126 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3859418" @default.
- W2000220126 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24200689" @default.
- W2000220126 hasPublicationYear "2013" @default.
- W2000220126 type Work @default.
- W2000220126 sameAs 2000220126 @default.
- W2000220126 citedByCount "155" @default.
- W2000220126 countsByYear W20002201262013 @default.