The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.

ObjectivesTo perform a genome-wide association study (GWAS) of gout cases versus asymptomatic hyperuricaemia (AH) controls, and gout cases versus normouricaemia controls, and to generate a polygenic risk score (PRS) to determine gout-case versus AH-control status.MethodsGout cases and AH controls (serum urate (SU) ≥6.0 mg/dL) from the UK Biobank were divided into discovery (4934 cases, 56 948 controls) and replication (2115 cases, 24 406 controls) cohorts. GWAS was conducted and PRS generated using summary statistics in discovery cohort as the base dataset and the replication cohort as the target dataset. The predictive ability of the model was evaluated. GWAS were performed to identify variants associated with gout compared with normouricaemic controls using SU <6.0 mg/dL and <7.0 mg/dL thresholds, respectively.ResultsThirteen independent single nucleotide polymorphisms (SNPs) in ABCG2, SLC2A9, SLC22A11, GCKR, MEPE, PPM1K-DT, LOC105377323 and ADH1B reached genome-wide significance and replicated as predictors of AH to gout transition. Twelve of 13 associations were novel for this transition, and rs1229984 (ADH1B) was identified as GWAS locus for gout for the first time. The best PRS model was generated from association data of 17 SNPs; and had predictive ability of 58.5% that increased to 69.2% on including demographic factors. Two novel SNPs rs760077(MTX1) and rs3800307(PRSS16) achieved GWAS significance for association with gout compared with normouricaemic controls using both SU thresholds.ConclusionThe association of urate transporters with gout supports the central role of hyperuricaemia in its pathogenesis. Larger GWAS are required to identify if variants in inflammatory pathways contribute to progression from AH to gout.

ObjectiveTo estimate the prevalence and distribution of asymptomatic monosodium urate monohydrate (MSU) crystal deposition in sons of patients with gout.MethodsPatients with gout were mailed an explanatory letter with an enclosed postage‐paid study packet to mail to their son(s) age ≥20 years old. Sons interested in participating returned a reply form and underwent telephone screening. Subsequently, they attended a study visit at which blood and urine samples were obtained and musculoskeletal ultrasonography was performed, with the sonographer blinded with regard to the subject's serum urate level. Images were assessed for double contour sign, intraarticular or intratendinous aggregates/tophi, effusion, and power Doppler signal. Logistic regression was used to examine associations. Adjusted odds ratios (OR adj) and 95% confidence intervals (95% CIs) were calculated.ResultsOne hundred thirty‐one sons (mean age 43.8 years, mean body mass index 27.1 kg/m2) completed assessments. The serum urate level was ≥6 mg/dl in 64.1%, and 29.8% had either a double contour sign or intraarticular aggregates/tophi in ≥1 joint. All participants with MSU deposition had involvement of 1 or both first metatarsophalangeal joints. Intratendinous aggregates were present in 21.4% and were associated with intraarticular MSU crystal deposits (OR adj 2.96 [95% CI 1.17–7.49]). No participant with a serum urate level of ≤5 mg/dl had MSU crystal deposition seen on ultrasonography, and 24.2% of those with serum urate levels between 5 and 6 mg/dl had ultrasonographic MSU deposition. MSU crystal deposition was associated with increasing serum urate levels (OR adj 1.61 [95% CI 1.10–2.36] for each increase of 1 mg/dl).ConclusionAsymptomatic sons of patients with gout frequently have hyperuricemia and MSU crystal deposits. In this study MSU crystal deposits were present in participants with serum urate levels of ≥5 mg/dl. Evaluation of subjects without a family history of gout is needed to determine whether the threshold for MSU crystal deposition is also lower in the general population.

Objectives To examine the association between comorbidities and serum urate (SU), gout and comorbidities, and to determine whether the association between gout and comorbidities is independent of SU. Methods We performed a case–control study using UK Biobank data. Two separate analyses were conducted: one excluding participants with gout to investigate the association between comorbidities and SU and the other with participants with gout as the index condition to examine the association between gout and comorbidities. SU was measured at the baseline visit. Self-reported physician-diagnosed illnesses were used to define gout and comorbidities, except for chronic kidney disease (CKD), which was defined using an estimated glomerular filtration rate cut-off. Participants prescribed urate-lowering treatment were also classified as gout. Logistic regression was used to examine associations. Odds ratios (ORs) and 95% CIs were calculated and adjusted for covariates including comorbidities and SU. Results Data for 458 781 UK Biobank participants were used to examine the association between comorbidities and SU. There was an association between hypertension, ischaemic heart disease (IHD), congestive cardiac failure (CCF), hyperlipidaemia, CKD and SU with and adjusted OR (aOR) of 1.10–3.14 for each 1 mg/dl SU increase. A total of 10 265 gout cases and 458 781 controls were included in the analysis of association between gout and comorbidities. Gout associated independently with hypertension, IHD, CCF, hyperlipidaemia and diabetes, with aORs of 1.21–4.15 after adjusting for covariates including SU. Conclusion Comorbidities associate with increasing SU. The association between gout and cardiometabolic comorbidities was independent of SU, suggesting separate SU-independent mechanisms such as inflammation driven by crystal deposition, pro-inflammatory genotype or non-purine dietary factors.