IRF4 haploinsufficiency in a family with Whipple’s disease

Whipple's disease (WD) affects only a very small minority of individuals infected by Tropheryma whipplei (Tw). Asymptomatic and chronic carriage of the causative organism is less rare and therefore, the pathogenesis of WD is poorly understood. Here we studied transcriptome responses in peripheral blood mononuclear cells (PBMCs) that were obtained from members of a large multiplex French kindred including otherwise healthy WD patients, healthy chronic carriers of Tw and other unrealted control subjects. PBMCs from six IRF4-heterozygous individuals (three patients, P1-P3; and three healthy relatives, HET1-HET3) and six IRF4 WT-homozygous individuals (four healthy relatives, WT1-WT4; and two unrelated controls, C1-C2) were dispensed into a 96-well plate and were either infected in vitro with live Tw at a multiplicity of infection (MOI) of 1, with live BCG (M. bovis-BCG, Pasteur substrain) at a MOI of 20, or were left uninfected (mock). Two wells per condition were combined 24 h post-infection for total RNA isolation followed by microarray analysis.