Alterations In HLA-DR Expression In Peripheral Blood Mononuclear Cells Are Associated with An Elevated Tricuspid Regurgitant Jet Velocity and Pulmonary Hypertension of Sickle Cell Disease
2010
Abstract 2640 Sickle cell anemia (SCA) is characterized by a chronic inflammatory vasculopathy. An elevated tricuspid regurgitant jet velocity (TRV) by echocardiography in SCA patients is not only reflective of possible pulmonary hypertension but is also associated with increased mortality risk, relative systemic hypertension, and renal disease, all of which suggest this is a marker of a more diffuse vasculopathy. We hypothesized that differential gene expression in peripheral blood mononuclear cells (PBMCs) occurs in SCA patients with an elevated TRV and might reflect the role of inflammation in sickle vasculopathy. Peripheral blood samples were obtained from 15 steady-state SCA patients (7 of whom had a TRV > 2.5 m/sec). Three cases with increased TRV had right heart catheterization that confirmed the presence of pulmonary hypertension. PBMCs were isolated via a Ficoll separation. RNA was isolated and amplified using the Ambion Illumina Total RNA Prep Kit, and then hybridized to Illumina Human HT-12 V3 Expression Bead Chips and scanned. Expression data was background corrected, log-transformed, and strictly filtered to consider only probes showing expression in each sample and significant expression in at least half of either group of samples. Differential expression was tested for significance using a t-test performed on both native and rescaled datasets, and only probes reaching a significance of p MYOM2 , observed almost exclusively in SCA patients with a normal echocardiogram (p=0.007 and 0.008 respectively). Differential PBMC gene expression across the HLA-DRB1 locus has been associated in other populations with impaired immunity and increased susceptibility to sepsis. Our previous genetic studies have identified a potential link between the HLA loci and leg ulcers, another hemolytic complication associated with an elevated TRV in 219 SCA cases when compared with 1180 controls. In those studies, HLA-B was found to be in linkage disequilibrium with 3 genes found to be significantly associated with leg ulcers. This suggests the possibility that these heritable loci may play a role in disease modulation in SCD. PBMCs in SCA patients might have a pro-inflammatory phenotype and this may play a role in the vasculopathy and increased mortality risk observed in these patients. Disclosures: No relevant conflicts of interest to declare.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI