The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications.

ObjectivesCOVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination.DesignProspective observational cross-sectional study.SettingSecondary care tertiary hospital in the UK.ParticipantsThis study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021).Outcome measuresAssociations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively.Results322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44).ConclusionsPatients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.

Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of multiple lipids in the late endosome/lysosomal system and reduced acidic store calcium. The lysosomal system regulates key aspects of iron homeostasis, which prompted us to investigate whether there are hematological abnormalities and iron metabolism defects in NPC1. Methods: Iron-related hematological parameters, systemic and tissue metal ion and relevant hormonal and proteins levels, expression of specific pro-inflammatory mediators and erythrophagocytosis were evaluated in an authentic mouse model and in a large cohort of NPC patients. Results: Significant changes in mean corpuscular volume and corpuscular hemoglobin were detected in Npc1-/- mice from an early age. Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron deficiency, increased circulating hepcidin, decreased ferritin and abnormal pro-inflammatory cytokine levels were also found. Furthermore, there is evidence of defective erythrophagocytosis in Npc1-/- mice and in an in vitro NPC1 cellular model. Comparable hematological changes, including low normal serum iron and transferrin saturation and low cerebrospinal fluid ferritin were confirmed in NPC1 patients. Conclusions: These data suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease.

No abstract