Antiviral response and HIV-1 inhibition in sickle cell disease.

Sickle cell disease (SCD) is characterized by hemolysis, vaso-occlusion, and ischemia. HIV-1 infection was previously shown to be suppressed in SCD PBMCs. Here, we report that HIV-1 suppression is attributed to the increased expression of iron, hypoxia, and interferon-induced innate antiviral factors.

Restriction of HIV-1 infection in sickle cell trait.

Patients with sickle cell disease (SCD) have a lower risk for HIV-1 infection. We reported restriction of ex vivo HIV-1 infection in SCD peripheral blood mononuclear cells (PBMCs) that was due, in part, to the upregulation of antiviral, inflammatory, and hemolytic factors, including heme oxygenase-1 (HO-1). Here, we investigated whether individuals with sickle cell trait (SCT), who develop mild hemolysis, also restrict HIV-1 infection.

Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease.

The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1).

Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin.

Ferroportin Q248H mutation has an allele frequency of 2.2-13.4% in African populations and is associated with a mild tendency to increased serum ferritin in the general population.

Dietary iron intake and serum ferritin concentration in 213 patients homozygous for the HFEC282Y hemochromatosis mutation.

Background: HFEC282Y homozygotes have an increased risk for developing increased iron stores and related disorders. It is controversial whether dietary iron restrictions should be recommended to such individuals.

Objective: To determine whether dietary iron content influences iron stores in HFEC282Y homozygotes as assessed by serum ferritin concentration.

Complete blood count, measures of iron status and inflammatory markers in inner-city African Americans with undiagnosed hepatitis C seropositivity.

Background: Hepatitis C virus (HCV) infection may be associated with thrombocytopenia and increased iron stores in patients receiving medical care. We aimed to determine how often changes in hematologic, iron metabolic and inflammatory markers occur in individuals with undiagnosed HCV in the community.

Methods: Inner-city African Americans (n=143) were recruited from the community according to reported ingestion of alcohol.

Potential nonresponse bias in a clinical examination after initial screening using iron phenotyping and HFE genotyping in the hemochromatosis and iron overload screening study.

Background: Little is known about the factors affecting participation in clinical assessments after HEmochromatosis and IRon Overload Screening.

Methods: Initial screening of 101,168 primary care patients in the HEmochromatosis and IRon Overload Screening study was performed using serum iron measures and hemochromatosis gene (HFE) genotyping. Using iron phenotypes and HFE genotypes, we identified 2256 cases and 1232 controls eligible to participate in a clinical examination.

Echocardiographic findings in patients with sickle cell disease.

Pulmonary hypertension is a complication of sickle cell disease that is associated with increased mortality. Whether this complication is associated with hemolysis has been questioned. Systolic pulmonary artery blood pressure can be estimated from echocardiography-determined tricuspid regurgitation velocity (TRV).

Ferroportin Q248h, dietary iron, and serum ferritin in community African-Americans with low to high alcohol consumption.

Background: Alcohol consumption is associated with increased iron stores. In sub-Saharan Africa, high dietary ionic iron and the ferroportin Q248H allele have also been implicated in iron accumulation. We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African-Americans.

Results communication and patient education after screening for possible hemochromatosis and iron overload: experience from the HEIRS Study of a large ethnically and linguistically diverse group.

Purpose: We assessed the effectiveness of educational interventions for conveying clinical findings and information about hereditary hemochromatosis (HH) and iron overload (IO) to individuals evaluated clinically after initial screening for HH/IO with serum ferritin (SF) concentration, transferrin saturation (TS), and HFE genotyping.

Methods: A questionnaire mailed to 2300 cases and controls 1 month after a letter summarizing clinical findings measured understanding of results and recommendations, knowledge of HH/IO, and satisfaction with information received.

Results: Of 1622 (70.