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Hum Immunol. 2013 Sep;74(9):1184-93. doi: 10.1016/j.humimm.2013.06.020. Epub 2013 Jun 18.

Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis.

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Department of Internal Medicine II, University of Tuebingen, Otfried-Muller-Str. 10, 72076 Tuebingen, Germany.


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.


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

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