Nuffield Orthopaedic Centre

About: Nuffield Orthopaedic Centre is a healthcare organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Arthroplasty. The organization has 2082 authors who have published 2920 publications receiving 145718 citations.

Common variants within the interleukin 4 receptor α gene (IL4R) are associated with susceptibility to osteoarthritis

Abstract: Primary osteoarthritis (OA) is a common late-onset arthritis that demonstrates a complex mode of transmittance with both joint-site and gender-specific heterogeneity. We have previously linkage-mapped an OA susceptibility locus to a 12-cM interval at chromosome 16p12.3-p12.1 in a cohort of 146 affected female sibling-pair families ascertained by total hip replacement (female-THR families), with a maximum multipoint LOD score of 1.7. Despite the low LOD score, we were encouraged to investigate this interval further following the report of a linkage to the same interval in an Icelandic pedigree with an early-onset form of hip OA. Using public databases, we searched the interval for plausible candidates and concluded that the gene encoding the interleukin 4 receptor α chain (IL4R) was a particularly strong candidate based on its known role in cartilage homeostasis. We genotyped nine common single nucleotide polymorphisms (SNPs) from within IL4R, including six non-synonymous SNPs, in the 146 probands from our female-THR families (stage 1) and in an independent cohort of 310 female-THR cases (stage 2). We compared allele frequencies with those of 399 age-matched female controls. All individuals were UK Caucasians. The minor alleles of two SNPs demonstrated association in both stages, with the most significant association having a P-value of 0.004 with an odds ratio (OR) of 2.1. These two SNPs defined two associated SNP groups. Inheriting a minor SNP allele from both groups was a particular risk factor (OR=2.4, P=0.0008). Our data suggest that functional variants within the IL4R gene predispose to hip OA in Caucasian females.

Corticosteroids and osteoporosis.

Abstract: The undoubted benefits of therapeutic corticosteroids carry a high price in side effects. Prominent among these is extensive loss of trabecular bone with widespread structural collapse. As in practice the good and the bad effects cannot be separated, the prevention and treatment of iatrogenic corticosteroid osteoporosis has been a largely ineffectual compromise (for reviews see refs 1-6). Recent investigations of the microstructure and histomorphometry of this form of osteoporosis and advances in new forms of treatment now provide a more logical basis for its management."~

Mri after operative reduction for developmental dysplasia of the hip

Abstract: We performed MRI on 13 infants after operative reduction for developmental dysplasia of the hip (DDH). Using an axial gradient-echo sequence, MRI accurately depicted the acetabular anatomy and confirmed adequate reduction in 12 patients. The one patient with redislocation after surgery was correctly identified. MRI can be carried out quickly, inexpensively and without risk of radiation and is the investigation of choice to confirm adequate reduction in DDH.

Inhibiting HLA-B27 homodimer-driven immune cell inflammation in spondylarthritis.

Abstract: Objective Spondylarthritides (SpA), including ankylosing spondylitis (AS), are common inflammatory rheumatic diseases that are strongly associated with positivity for the HLA class I allotype B27. HLA–B27 normally forms complexes with β2-microglobulin (β2m) and peptide to form heterotrimers. However, an unusual characteristic of HLA–B27 is its ability to form β2m-free heavy chain homodimers (HLA–B272), which, unlike classic HLA–B27, bind to killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). Binding of HLA–B272 to KIR-3DL2–positive CD4+ T and natural killer (NK) cells stimulates cell survival and modulates cytokine production. This study was undertaken to produce an antibody to HLA–B272 in order to confirm its expression in SpA and to inhibit its proinflammatory properties. Methods We generated monoclonal antibodies by screening a human phage display library positively against B272 and negatively against B27 heterotrimers. Specificity was tested by enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR) assay, and fluorescence-activated cell sorting (FACS) analysis of B272-expressing cell lines and peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with SpA. Functional inhibition of KIR-3DL2–B272 interactions was tested using cell lines and PBMCs from patients with SpA. Results Monoclonal antibody HD6 specifically recognized recombinant HLA–B272 by ELISA and by SPR assay. HD6 bound to cell lines expressing B272. FACS revealed binding of HD6 to PBMCs and SFMCs from patients with AS but not from controls. HD6 inhibited both the binding of HLA–B272 to KIR-3DL2 and the survival and proliferation of KIR-3DL2–positive NK cells. Finally, HD6 inhibited production of the proinflammatory disease–associated cytokine interleukin-17 by PBMCs from patients with AS. Conclusion These results demonstrate that antibody HD6 has potential for use in both the investigation and the treatment of AS and other B27-associated spondylarthritides.