variant-expressing endothelial cells exhibit autophagic dysfunction and mitochondrial stress.

Polymorphisms in the Apolipoprotein L1 () gene are common in ancestrally African populations, and associate with kidney injury and cardiovascular disease. These risk variants (RV) provide an advantage in resisting , the causal agent of African trypanosomiasis, and are largely absent from non-African genomes. Clinical associations between the high risk genotype (HRG) and disease are stronger in those with comorbid infectious or immune disease.

Human low-affinity IgG receptor FcγRIIA polymorphism H131R associates with subclinical atherosclerosis and increased platelet activity in systemic lupus erythematosus.

Essentials Systemic lupus erythematosus (SLE) patients are at increased risk for premature CVD. Platelet activity, vascular dysfunction and carotid artery plaque are associated with FcγRIIA genotype in SLE. FcγRIIA genotype was not associated with platelet activity or carotid plaque in healthy controls.

Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block.

Given that diseases associated with anti-SSA/Ro autoantibodies, such as systemic lupus erythematosus and Sjögren syndrome, are linked with an upregulation of IFN and type I IFN-stimulated genes, including sialic acid-binding Ig-like lectin 1 (Siglec-1), a receptor on monocytes/macrophages, recent attention has focused on a potential role for IFN and IFN-stimulated genes in the pathogenesis of congenital heart block (CHB). Accordingly, three approaches were leveraged to address the association of IFN, IFN-stimulated genes, and the phenotype of macrophages in affected fetal cardiac tissue: 1) cultured healthy human macrophages transfected with hY3, an anti-SSA/Ro-associated ssRNA, 2) RNA isolated from freshly sorted human leukocytes/macrophages after Langendorff perfusion of three fetal hearts dying with CHB and three healthy gestational age-matched hearts, and 3) autopsy tissue from three additional human CHB hearts and one healthy heart. TLR ligation of macrophages with hY3 led to the upregulation of a panel of IFN transcripts, including SIGLEC1, a result corroborated using quantitative PCR.

Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA.

Reactivity to the p305 Epitope of the α1G T-Type Calcium Channel and Autoimmune-Associated Congenital Heart Block.

Background: Only 2% of mothers positive for anti-SSA/Ro (Ro) antibodies have children with congenital heart block (CHB). This study aimed to determine whether reactivity with p305, an epitope within the α1G T-type calcium channel, confers added risk over anti-Ro antibodies.

Methods And Results: Using sera from anti-Ro-exposed pregnancies resulting in offspring with CHB, no disease but CHB-sibling, and no disease and no CHB-sibling, as well as disease (lupus without anti-Ro) and healthy controls, reactivities were determined for binding to Ro60, p305, and an epitope within Ro60, p133-Ro60, which shares structural properties with p305, including key amino acids and an α-helical structure.