Nonadherence to antihypertensive medications is related to pill burden in apparent treatment-resistant hypertensive individuals.

OBJECTIVE: Nonadherence to medication is present in at least 50% of patients with apparent treatment-resistant hypertension. We examined the factors associated with nonadherence as detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based urine antihypertensive drug assay. METHODS: All urine antihypertensive test results, carried out for uncontrolled hypertension (BP persistently >140/90 mmHg) between January 2015 and December 2016 at a single toxicology laboratory were analysed. Drugs detected were compared with the antihypertensive drugs prescribed. Patients were classified as adherent (all drugs detected), partially nonadherent (at least one prescribed drug detected) or completely nonadherent (no drugs detected). Demographic and clinical parameters were compared between the adherent and nonadherent groups. Binary logistic regression analysis was performed to determine association between nonadherence and demographic and clinical factors. RESULTS: Data on 300 patients from nine hypertension centres across the United Kingdom were analysed. The median age was 59 years, 47% women, 71% Caucasian, median clinic BP was 176/95 mmHg and the median number of antihypertensive drugs prescribed was four. One hundred and sixty-six (55%) were nonadherent to prescribed medication with 20% of these being completely nonadherent. Nonadherence to antihypertensive medication was independently associated with younger age, female sex, number of antihypertensive drugs prescribed, total number of all medications prescribed (total pill burden) and prescription of a calcium channel blocker. CONCLUSION: This LC-MS/MS urine analysis-based study suggests the majority of patients with apparent treatment-resistant hypertension are nonadherent to prescribed treatment. Factors that are associated with nonadherence, particularly pill burden, should be taken into account while treating these patients.

The role of molecular mimicry and other factors in the association of Human Endogenous Retroviruses and autoimmunity.

Human Endogenous Retroviruses (HERVs) have been implicated in autoimmune and other diseases. Molecular mimicry has been postulated as a potential mechanism of autoimmunity. Exogenous viruses have also been reported to be associated with the same diseases, as have genetic and environmental factors. If molecular mimicry were to be shown to be an initiating mechanism of some autoimmune diseases, then therapeutic options of blocking antibodies and peptides might be of benefit in halting diseases at the outset. Bioinformatic and molecular modelling techniques have been employed to investigate molecular mimicry and the evidence for the association of HERVs and autoimmunity is reviewed. The most convincing evidence for molecular mimicry is in rheumatoid arthritis, where HERV K-10 shares amino acid sequences with IgG1Fc, a target for rheumatoid factor. Systemic lupus erythematosus is an example of a condition associated with several autoantibodies, and several endogenous and exogenous viruses have been reported to be associated with the disease. The lack of a clear link between one virus and this condition, and the spectrum of clinical manifestations, suggests that genetic, environmental and the inflammatory response to a virus or viruses might also be major factors in the pathogenesis of lupus and other autoimmune conditions. Where there are strong associations between a virus and an autoimmune condition, such as in hepatitis C and cryoglobulinaemia, the use of bioinformatics and molecular modelling can also be utilized to help to understand the role of molecular mimicry in how HERVs might trigger disease.

Rheumatoid arthritis is associated with IgG antibodies to human endogenous retrovirus gag matrix: a potential pathogenic mechanism of disease?

OBJECTIVE: Human endogenous retrovirus (HERV)-K10 has been implicated in the etiology and pathogenesis of rheumatoid arthritis (RA). A secondary immune response to this virus might suggest an antigen-driven response in patients. The Gag region of HERV-K10 could provide a key epitope important for immunological reactivity. We investigated the presence of IgG antibodies to this region and assessed its significance in RA. METHODS: We determined an antigenic peptide on the matrix segment of HERV-K10 and developed an ELISA system to detect IgG antibodies in patients with RA and controls. The presence of antibodies to the matrix peptide (denoted as MAG1: RIGKELKQAGRKGNI) was correlated with patient details. RESULTS: On screening patients' serum, we found a significantly higher mean IgG antibody response to MAG1 in 30 patients with RA as compared to 23 patients with inflammatory bowel disease (p = 0.003), 29 patients with osteoarthritis (p = 0.001), and 43 healthy individuals (p = 0.002). Reactivity was not observed to a control peptide possessing a nonhomologous amino acid sequence. On evaluating clinical details with serological activity, no correlation with disease duration (p = 0.128), sex (p = 0.768), or rheumatoid factor status (p = 0.576) was found. CONCLUSION: A significantly elevated IgG antibody response to an HERV-K10 Gag matrix peptide was observed in patients with RA, suggesting that the exposure of HERV-K10 may cause a secondary, antigenic driven immune response in RA.