Analysis of SHIP1 expression and activity in Crohn's disease patients.

Authors :: Somasundaram R
Fernandes S
Deuring JJ
de Haar C
Kuipers EJ
Vogelaar L
Middleton FA
van der Woude CJ
Peppelenbosch MP
Kerr WG
Fuhler GM
Source :: PloS one [PLoS One] 2017 Aug 02; Vol. 12 (8), pp. e0182308. Date of Electronic Publication: 2017 Aug 02 (Print Publication: 2017).
Publication Year :: 2017
Abstract: Background: SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn's disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients.<br />Methods: SHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880.<br />Results: SHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort.<br />Conclusions: Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.