Classification of systemic lupus erythematosus in children and adults.

Systemic Lupus Erythematosus (SLE) is an autoimmune multisystem disease with a variable clinical phenotype and no single clinical, laboratory or pathological feature that can be used as a gold standard for disease classification or diagnosis. Classification criteria have been developed in an attempt to define homogenous groups of SLE patients for clinical research. They have been mainly validated in adult cohorts, given the much lower prevalence of SLE before puberty. The three commonly used sets of current classification criteria and their validation studies to date are described in this review. Challenges relating to classification of SLE patients, including important differences across age-groups and ethnicities, are explored along with future directions in the classification of SLE.

Defining consensus opinion to develop randomised controlled trials in rare diseases using Bayesian design: An example of a proposed trial of adalimumab versus pamidronate for children with CNO/CRMO.

INTRODUCTION: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder primarily affecting children and adolescents. It can lead to chronic pain, bony deformities and fractures. The pathophysiology of CNO is incompletely understood. Scientific evidence suggests dysregulated expression of pro- and anti-inflammatory cytokines to be centrally involved. Currently, treatment is largely based on retrospective observational studies and expert opinion. Treatment usually includes nonsteroidal anti-inflammatory drugs and/or glucocorticoids, followed by a range of drugs in unresponsive cases. While randomised clinical trials are lacking, retrospective and prospective non-controlled studies suggest effectiveness of TNF inhibitors and bisphosphonates. The objective of the Bayesian consensus meeting was to quantify prior expert opinion. METHODS: Twelve international CNO experts were randomly chosen to be invited to a Bayesian prior elicitation meeting. RESULTS: Results showed that a typical new patient treated with pamidronate would have an 84% chance of improvement in their pain score relative to baseline at 26 weeks and an 83% chance on adalimumab. Experts thought there was a 50% chance that a new typical patient would record a pain score of 28mm (pamidronate) to 30mm (adalimumab) or better at 26 weeks. There was a modest trend in prior opinion to indicate an advantage of pamidronate vs adalimumab, with a 68% prior chance that pamidronate is superior to adalimumab by some margin. However, it is clear that there is considerable uncertainty about the precise relative merits of the two treatments. CONCLUSIONS: The rarity of CNO leads to challenges in conducting randomised controlled trials with sufficient power to provide a definitive outcome. We address this using a Bayesian design, and here describe the process and outcome of the elicitation exercise to establish expert prior opinion. This opinion will be tested in the planned prospective CNO study. The process for establishing expert consensus opinion in CNO will be helpful for developing studies in other rare paediatric diseases.

Evaluation of the ACR and SLICC classification criteria in juvenile-onset systemic lupus erythematosus: a longitudinal analysis.

Objectives The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients' classification criteria evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period). Results A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012. Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.

Development of an anti-Salmonella typhi Vi ELISA: assessment of immunocompetence in healthy donors.

We have developed a solid-phase enzyme-linked immunosorbent assay (ELISA) to study the vaccination responses to Vi capsular polysaccharide of Salmonella typhi (S. typhi Vi) vaccine. Purified S. typhi Vi polysaccharide was biotinylated and bound to streptavidin coated microtitre plates. Reproducibility was determined across a range of IgG antibody levels: mean interassay coefficients of variation (CVs) were <11.9% for non-vaccinated sera with low levels and <11.1% for sera with very high levels of anti-S. typhi Vi IgG. Specificity was assessed by inhibition studies using salmonella antigen. We have developed the ELISA based on normal adult serum responses to test immunization with S. typhi Vi vaccine. We also report here anti-S. typhi Vi IgG levels in a group of healthy preschool children. In non-vaccinated adult sera (n = 104), the median value of anti-S. typhi Vi IgG, expressed in S. typhi Vi arbitrary units (AU/ml), was 5.3 AU/ml and in non-vaccinated sera from children (n = 44) the median value was 1.4 AU/ml. The data from immunization of healthy volunteers (n = 23) show that geometric mean levels of anti-S. typhi Vi IgG were significantly higher (P < 0.0001) for post-vaccination subjects (39.2 AU/ml) compared to paired prevaccination (3.9 AU/ml) values. A total of 21/23 vaccine recipients had <8 AU/ml S. typhi Vi IgG in their sera prior to vaccination and of these 20/21 (95%) exhibited threefold increases and 14/21 (67%) fourfold increases in their S. typhi Vi IgG following vaccination. Based on the data in this study, we propose a threefold increase in anti-S. typhi Vi IgG post-vaccination to be considered a positive vaccination response. The ability to demonstrate clearly an antibody rise in response to immunization with S. typhi Vi capsular polysaccharide vaccine suggests that this is likely to be a useful vaccine for the assessment of B cell function in patients with suspected immune deficiency.