Proliferation of Tγ-lymphocytes in two patients: Clinical features and functional properties of the proliferating cells.

Two patients suffering from proliferation of Tγ cells exhibited uncommon clinical features, such as activation of intravascular coagulation after low dose irradiation of the enlarged spleen in one patient and isolated neutropenia in the other patient. While the malignant nature of the disease was doubtless in one patient, cell proliferation in the other patient was more likely reactive. In addition to T cell determinants the proliferating cells expressed a monocytic antigen. They did not suppress B-lymphocyte differentiation into plasma cells. In contrast the proliferating cells, especially in one patient, acted as potent effectors in NK and ADCC using melanoma and MOLT 4 target cells. Erythrophagocytosis by Tγ cells was seen in one patient. The data suggest that subsets of Tγ cells are related to the monocytic lineage and that these cells can mediate both NKA and ADCC and partly can develop phagocytic activity

Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies.

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the brain. The results show an enrichment for monogenic epilepsy genes as well as known targets of antiepileptic drugs. Using SNP-based heritability analyses we disentangle both the unique and overlapping genetic basis to seven different epilepsy subtypes. Together, these findings provide leads for epilepsy therapies based on underlying pathophysiology