Targeted Delivery of Chloroquine to Antigen-Presenting Cells Enhances Inhibition of the Type I Interferon Response.

Systemic lupus erythematosus (SLE) causes damaging inflammation in multiple organs via the accumulation of immune complexes. These complexes activate plasmacytoid dendritic cells (pDCs) via toll-like receptors (TLRs), contributing to disease pathogenesis by driving the secretion of inflammatory type I interferons (IFNs). Antimalarial drugs, such as chloroquine (CQ), are TLR antagonists used to alleviate inflammation in SLE. However, they require ∼3 months of continuous use before achieving therapeutic efficacy and can accumulate in the retinal pigment epithelium with chronic use, resulting in retinopathy. We hypothesized that poly(ethylene glycol)-b-poly(propylene sulfide) filamentous nanocarriers, filomicelles (FMs), could directly deliver CQ to pDCs via passive, morphology-based targeting to concentrate drug delivery to specific immune cells, improve drug activity by increased inhibition of type I IFN, and enhance efficacy per dose. Healthy human peripheral blood mononuclear cells were treated with soluble CQ or CQ-loaded FMs, stimulated with TLR agonists or SLE patient sera, and type I IFN secretion was quantified via multi-subtype IFN-α ELISA and MX1 gene expression using real-time reverse transcription-quantitative polymerase chain reaction. Our results showed that 50 µg CQ/mg FM decreased MX1 expression and IFN-α production after TLR activation with either synthetic nucleic acid agonists or immune complex-rich sera from SLE patients. Cellular uptake and biodistribution studies showed that FMs preferentially accumulate in human pDCs and monocytes in vitro and in tissues frequently damaged in SLE patients (i.e., kidneys), while sparing the eye in vivo. These results showed that nanocarrier morphology enables drug delivery, and CQ-FMs may be equally effective and more targeted than soluble CQ at inhibiting SLE-relevant pathways.

Leveraging Heterogeneity in Systemic Lupus Erythematosus for New Therapies.

Systemic lupus erythematosus (SLE) is a multisystem, chronic autoimmune disease where treatment varies by patient and disease activity. Strong preclinical results and clinical correlates have motivated development of many drugs, but many of these have failed to achieve efficacy in clinical trials. FDA approval of belimumab in 2011 was the first successful SLE drug in nearly six decades. In this article, we review insights into the molecular and clinical heterogeneity of SLE from transcriptomics studies and detail their potential impact on drug development and clinical practices. We critically examine the pipeline of SLE drugs, including past failures and their associated lessons and current promising approaches. Finally, we identify opportunities for integrating these findings and drug development with new multidisciplinary advances to enhance future SLE treatment.

International classification of traditional medicine.

The International Classification of Diseases (ICD) provides alphanumeric codes that have a longstanding place in the annals of contemporary medicine for epidemiology, health management, and clinical diagnoses from patient encounters to death certificates. This system is maintained by the World Health Organization (WHO). Traditional medicine (TM) has historical usage patterns established by treating people through the centuries but has never before been included in the ICD code set. The inclusion of traditional Asian medicine in the International Family of Classifications is a new venture and scheduled to be included in the ICD-11 revision of the codes. This may enable the comparison of diagnostic, clinical outcome, and epidemiological information across medical systems. WHO recently completed a survey among member nations and discovered that 82% of the world's population uses some form of TM.(2.)

Role of food labels in accidental exposures in food-allergic individuals in Canada.

BACKGROUND: Little is known about the impact of food labeling on the allergic consumer. OBJECTIVE: To determine the proportion of food-allergic individuals attributing an accidental exposure to inappropriate labeling, failure to read a food label, or ignoring a precautionary statement and to identify factors associated with accidental exposures. METHODS: Food-allergic individuals or their caregivers were recruited from a Canadian registry of individuals with a physician-confirmed diagnosis of peanut allergy and from allergy awareness organizations. Participants completed questionnaires regarding accidental exposures due to specific food labeling issues. The association between accidental exposures and characteristics of food-allergic individuals or their caregivers was estimated using multivariate logistic regression models. RESULTS: Of 1,862 potential participants, 1,454 (78.1%) responded. Of the 47.8% (95% confidence interval [CI], 45.1%-50.5%) of respondents who experienced an accidental exposure, 47.0% (95% CI, 43.1%-50.9%) attributed the event to inappropriate labeling, 28.6% (95% CI, 25.1%-32.2%) to failure to read a food label, and 8.3% (95% CI, 6.3%-10.7%) to ignoring a precautionary statement. Food-allergic individuals who were allergic to peanut, tree nut, fish, or shellfish were less likely to experience an accidental exposure due to the allergen not being identified in plain language. CONCLUSIONS: A considerable proportion of accidental exposures are attributed to inappropriate labeling, failure to read labels, and ignoring precautionary statements. Clear and consistent labeling of food allergens combined with increased consumer education is necessary to improve consumer confidence and compliance and to reduce accidental exposures.