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

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.