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

Human immunology

PubMedID: 23792059

Klein R, Marx A, Ströbel P, Schalke B, Nix W, Willcox N. Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis. Hum Immunol. 2013;74(9):1184-93.
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.