PMID- 33970749 OWN - NLM STAT- MEDLINE DCOM- 20220401 LR - 20220401 IS - 1744-8352 (Electronic) IS - 1473-7159 (Linking) VI - 21 IP - 6 DP - 2021 Jun TI - Improving laboratory diagnostics in myasthenia gravis. PG - 579-590 LID - 10.1080/14737159.2021.1927715 [doi] AB - Introduction: Myasthenia gravis (MG) is a prototypical autoimmune disease, characterized by pathogenic autoantibodies targeting structures of the neuromuscular junction. Radioimmunoprecipitation assays (RIPAs) represent the gold standard for their detection. However, new methods are emerging to complement, or overcome RIPAs, also with the perspective of eliminating the use of radioactive reagents.Areas covered: We discuss advances in laboratory methods, prompted especially by cell-based assays (CBAs), for the detection of the autoantibodies of MG diagnostics, above all those to the nicotinic acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low molecular-weight receptor-related low-density lipoprotein-4 (LRP4).Expert opinion: CBA technology makes AChRs aggregate on cell membranes, thus allowing to detect autoantibodies to clustered AChRs, with reduction of seronegative MG cases. The diagnostic relevance of RIPA/CBA-measurable LRP4 antibodies is still unclear, in Caucasian patients at least. Live CBAs for the detection of AChR, MuSK, and LRP4 antibodies might represent an alternative to RIPAs, but first require full validation. CBAs could be used as screening tests, limiting RIPAs for antibody quantification. To this end, ELISAs might be an alternative.Fixation procedures preserving enough degree of antigen conformationality could yield AChR and MuSK CBAs suitable for a wide use in clinical-chemistry laboratories. FAU - Gastaldi, Matteo AU - Gastaldi M AD - Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy. FAU - Scaranzin, Silvia AU - Scaranzin S AD - Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy. FAU - Businaro, Pietro AU - Businaro P AD - Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. FAU - Mobilia, Emanuela AU - Mobilia E AD - Autoimmunity Laboratory, IRCCS Ospedale Policlinico San Martino, Genova, Italy. FAU - Benedetti, Luana AU - Benedetti L AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy. FAU - Pesce, Giampaola AU - Pesce G AD - Autoimmunity Laboratory, IRCCS Ospedale Policlinico San Martino, Genova, Italy. AD - Department of Internal Medicine (Dimi), University of Genova, Genova, Italy. FAU - Franciotta, Diego AU - Franciotta D AD - Autoimmunity Laboratory, IRCCS Ospedale Policlinico San Martino, Genova, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210519 PL - England TA - Expert Rev Mol Diagn JT - Expert review of molecular diagnostics JID - 101120777 RN - 0 (Autoantibodies) SB - IM MH - Autoantibodies MH - Biological Assay MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - *Myasthenia Gravis/diagnosis OTO - NOTNLM OT - Autoantibody OT - cell-based assay OT - enzyme-linked immunosorbent assay OT - laboratory diagnostics OT - low molecular weight receptor related low-density lipoprotein 4 OT - muscle specific tyrosine kinase OT - myasthenia gravis OT - neuroimmunology OT - nicotinic acetylcholine receptor OT - radioimmunoprecipitation assay EDAT- 2021/05/11 06:00 MHDA- 2022/04/02 06:00 CRDT- 2021/05/10 17:29 PHST- 2021/05/11 06:00 [pubmed] PHST- 2022/04/02 06:00 [medline] PHST- 2021/05/10 17:29 [entrez] AID - 10.1080/14737159.2021.1927715 [doi] PST - ppublish SO - Expert Rev Mol Diagn. 2021 Jun;21(6):579-590. doi: 10.1080/14737159.2021.1927715. Epub 2021 May 19.