title: Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis.
abstract: Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG. Here, we analysed 226 EOMG-, 97 LOMG-, and 150 thymoma-patients for autoimmune disorders in themselves and their relatives. From 283 of them sera were tested for different organ- and non-organ-specific autoantibodies (autoAbs) by immunofluorescence test (IFT) and ELISA; genotyping was performed in 213 patients. Relatives with autoimmune disorders were reported by more patients with EOMG (40% of 210) than LOMG (20% of 89; p < 0.01) than thymomas (8% of 150; p < 0.001). In 150 genotyped EOMG-females, the known risk allele of the immuno-regulatory PTPN2 2 (R620W) appeared commoner in those with second autoimmune diseases (p ∼ 0.06), or with autoimmune relatives (p ∼ 0.03), than in those without. Organ-specific autoAbs were found in ∼ 30% of all MG-patients, autoAbs to striated muscle only in patients with thymoma-MG (62%) or LOMG (61%). Titers against adrenal cortex were lower in LOMG-patients. Disease-associated autoAbs against systemic targets or 'natural autoAbs' - except of autoAbs to nuclei - were uncommon in all groups (< 13%). Thus-with rare exceptions in EOMG and LOMG-we found minimal support for the notion that autoimmune patients have wide-ranging autoreactivity that causes disease only if it targets such Achilles' heels as the muscle acetylcholine receptor; even in thymoma-patients the autoAbs are sharply focused on a restricted range of muscle, cytokine and endocrine targets.
authors.affiliation: Department of Internal Medicine II, University of Tuebingen, Otfried-Muller-Str. 10, 72076 Tuebingen, Germany. reinhild.klein@med.uni-tuebingen.de
authors.forename: Reinhild
authors.initials: R
authors.lastname: Klein
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Berthold
authors.initials: B
authors.lastname: Schalke
authors.forename: Wilfred
authors.initials: W
authors.lastname: Nix
authors.forename: Nick
authors.initials: N
authors.lastname: Willcox
mesh_terms: D000293:Adolescent; D000302:Adrenal Cortex / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D054792:Muscle, Striated / Q000276:immunology / Q000378:metabolism*; D009157:Myasthenia Gravis / Q000453:epidemiology*; D009928:Organ Specificity; D010375:Pedigree; D044382:Population Groups; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics / Q000378:metabolism; D013945:Thymoma / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2
keywords: AChR; AIRE; ANA; ANCA; ANCA with a cytoplasmic fluorescence pattern; ANCA with a perinuclear fluorescence pattern; APS-I; Autoimmune Polyendocrine Syndrome type I; CMC; ELISA; EOMG; GAD; GPC; GWAS; IDDM; IFN; IFT; IL; ITP; LOMG; MG; MS; NMO; NMT; NS; PA; PBC; PMR; PTPN22; RA; SD; SLE; TG; TNIP1; TPO; WHO; World Health Organization; acetylcholine receptor; anti-neutrophil cytoplasmic antibodies; anti-nuclear antibodies; auto-immune regulator; autoAb; autoAg; autoantibody; autoantigen; cANCA; chronic mucocutaneous candidiasis; double-stranded deoxyribonucleic acid; dsDNA; early-onset myasthenia gravis; enzyme-linked immuno-sorbent assay; gastric parietal cells; genome-wide association study; glutamic acid decarboxylase 65; idiopathic thrombocytopenic purpura; immunofluorescence test; insulin-dependent diabetes mellitus; interferon; interleukin; late-onset MG; multiple sclerosis; myasthenia gravis; neuro-myotonia; neuromyelitis optica; not significant; pANCA; pernicious anemia; polymyalgia rheumatica; primary biliary cirrhosis; protein tyrosine phosphatase, non-receptor type 22; rheumatoid arthritis; standard deviation; systemic lupus erythematosus; thyroglobulin; thyroid peroxidase; tumor necrosis factor α-induced protein 3-interacting protein 1