Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients

Musculoskeletal symptoms and non-prescribed treatments are common in an urban African population of people living with HIV.

There are no data from West Africa reporting musculoskeletal (MSK) disease in people living with HIV (PLWH). Our primary outcome was to measure the prevalence of MSK symptoms in PLWH in urban West Africa. Our secondary outcomes were to describe the disability, impact on work and treatment use associated with the presence of MSK pain. We conducted an e-questionnaire-based point prevalence study of musculoskeletal symptoms, associated disability and treatment in 292 PLWH attending routine follow-up in Lagos, Nigeria. Seventy-three (25%) patients reported MSK pain; 28 (38%) reported chronic symptoms (> 3 months). HIV suppression rates were high in this population (n = 240, 82%) and comparable between individuals with and without chronic pain. MSK pain was associated with female gender and higher body mass index (BMI). Mechanical pain was the most common pain syndrome identified (n = 34, 47%). Lumbar spine and knee were the most common sites. Chronic pain was associated with increased disability compared with the presence of any MSK pain. High rates of treatment-seeking behaviour were seen in those individuals reporting MSK pain (n = 62, 85%). The majority of these individuals sought traditional treatments (n = 48, 66%). Chronic MSK pain and non-prescribed treatments are common in PLWH established on ART in urban West Africa. Studies are required to measure the long-term impact of these symptoms and medicines on retention in HIV care and ART adherence, besides other long-term health outcomes

Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration

Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/cKit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors