Objective The objective of this study is to comprehensively define the genetic basis of Early Onset Myasthenia Gravis. Methods We have carried out a two-stage genome-wide association study on a total of 649 North European EOMG patients. Cases were matched 1:4 with controls of European ancestry. We performed imputation and conditional analyses across the major histocompatibility complex, as well as in the top regions of association outside the HLA region. Results We observed the strongest association in the HLA class I region at rs7750641 (p = 1.2 × 10−92, OR = 6.25). By imputation and conditional analyses, HLA-B*08 proves to be the major associated allele (p = 2.87 × 10−113, OR = 6.41). In addition to the expected association with PTPN22 (rs2476601, OR =1.71, p = 8.2 ×10−10), an imputed coding variant (rs2233290) at position 151 (Pro→Ala) in the TNFAIP3-interacting protein 1, TNIP1, confers even stronger risk than PTPN22 (OR = 1.91, p = 3.2 × 10−10). Interpretation The association at TNIP1 in EOMG implies disease mechanisms involving ubiquitin-dependent dysregulation of NF-κB signaling. The localization of the major HLA signal to the HLA-B*08 allele suggests that CD8+ T-cells may play a key role in disease initiation or pathogenesis.

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The prognosis for the majority of patients with MG is favourable, irrespective of thymic histology. The cause may be the use of immunomodulating therapy.

In this study 28 patients with early stage HIV infection (CD4 >280 x 10(6)/l) were subjected to yearly examinations of the nervous system up to 7 years in order to detect any deterioration. Clinical neurological as well as neuropsychological performance was evaluated. The patients also underwent yearly neurophysiological tests (digital EEG, visual evoked potentials, somatosensory evoked potentials, auditory evoked potentials P300 and electroneurography). Every other year, SPECT with (99m)Tc-D,L-hexamethylpropylene amine oxime and brain MRI were performed. Originally, 38 patients were included in the study but only the results of 28 patients who complied with three of more yearly check-ups are presented. The results of yearly investigations of cerebrospinal fluid (CSF) have been presented earlier [Eur J Neurol4 (1997) 1]. All the patients showed signs of HIV in the CSF. Yet, no major deterioration in the neurological, psychological performance, neurophysiological or neuroimaging examinations could be discerned.

The location of CMV in the brain corresponded well to the clinical findings, demonstrating the close relationship between the neurological symptoms and the neuroanatomical lesions.