Madeleine Rooney

Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis.

Immunohistological features which might predict the clinical course and outcome of rheumatoid arthritis were sought by examining multiple synovial membrane samples obtained by needle biopsy from the knee joints of 57 patients who had not received disease modifying antirheumatic drugs. Clinical measurements, but not biopsies, were repeated one year and three years after starting treatment. A correlation between both the intensity of synovial lining layer thickening and mononuclear cell infiltration and the clinical status at the time of biopsy was seen. After three years of treatment the correlations were maintained in patients who had presented and persisted with milder disease but not in patients who had presented with more active disease.

Biomarkers in rheumatology, now and in the future

This review examines the biomarker development process by using rheumatic disorders as the disease model for discussion. We evaluate the current role of biomarkers in the practice of rheumatology and discuss their likely role in the future. We define the essential components of the biomarker development pipeline and discuss the issue of fitness for purpose, i.e. what the biomarker(s) might offer in a clinical setting. As a component of this review we also highlight several emerging technologies that are beginning to provide practical solutions to support biomarker validation. In the process, we highlight some scenarios where additional biomarkers would add considerable value to clinical practice, and we review appropriate methods for each. We also emphasize some important but infrequently discussed considerations, including the need for protein variant verification. Ultimately, the adroit application of the methods of proteomics will transform the practice rheumatology and allow personalized clinical practice to become a reality.

Validation of Protein Biomarkers to Advance the Management of Autoimmune Disorders

Despite the anticipated boom stemming from proteomic investigations, the rate at whichnovel protein biomarkers are introduced into clinical practice has remained static over thepast 20 years. The reality is that approaches to both discover and validate proteinbiomarkers remain inadequate, and consequently, many areas of medicine, including thebroad field of autoimmune disorders, remain deprived of the tools essential for the optimalmanagement of patients. Most importantly, there is a huge backlog of candidate biomarkersthat are yet to undergo thorough investigation and validation to assess their clinical utility.A recent assessment of the situation has estimated that although many tens of thousands ofpublications claim biomarker discoveries, there are roughly only 100 routinely used inclinical practice (Poste, 2011).This chapter reviews the potential applications of protein biomarkers to manageautoimmune diseases with a special focus on the transition from the biomarker discoverythrough to validation phases using proteomic strategies. We emphasize the importance ofcareful review of the discovery data, the critical roles of protein isoform verification, and theessential features of targeted and thorough validation. Ultimately, when these factors areappropriately considered and implemented, we are optimistic that autoimmune disorderscan be transformed by omics technologies and personalized practice can become a reality.

Paediatric and Adolescent Rheumatology [143–150] 143. Knee Joint in JIA: A Prospective Evaluation of Clinical Examination, Ultrasound and Mri Assessment. A Newly Developed Knee MRI Scoring System in JIA

Background: Juvenile idiopathic arthritis (JIA) comprises a poorlyunderstood group of chronic, childhood onset, autoimmune diseaseswith variable clinical presentations, outcomes and therapeuticresponses. Current laboratory tests are unable to flag those patientsat a higher risk of disease spread to multiple joints, who could benefitform earlier therapy to prevent joint damage. This study was focusedon profiling the synovial fluid (SF) proteome associated with diseaseextension from oligo- to polyarticular status by a difference gelelectrophoresis (DIGE) approach.Methods: To construct a discriminant model, SF samples from 55 JIApatients were analysed: 30 oligo-, 8 extended oligo- and 17polyarticular disease. Initial SF samples from each patient werelabeled with Cy dyes and subjected to protein separation by 2-DE. Theability to distinguish patients at risk of disease extension by a selectgroup of proteins was illustrated by multivariate analysis methods.Proteins over expressed with a two-fold difference between patientsubgroups were identified by MALDI-TOF. Specific antibodies wereused to validate putative biomarker expression in synovial fluid bywestern immunoblotting and in synovial membrane (SM) byimmunohistochemistry.Results: Samespots software analysis of SF gel scans was used tohighlight joint-specific proteins which were differentially expressedacross disease classifications. Hierarchical clustering based on theexpression levels of a previously selected set of 40 proteins matchedacross the three clinical subgroups segregates the extended oligoarticularpatients. Proteolytic fragments of apolipoprotein AII, complementcomponent C3c and vitamin D binding protein were identified(P<0.05) amongst the discriminatory proteins. Apolipoprotein AIIand vitamin D binding protein were expressed at significantly higherlevels in the polyarticular patients, P¼0.046 and P¼0.019 respectively,both with a perivascular distribution in the SM.Conclusions: Synovial fluid proteome profiles have been used to flagJIA patients at risk of disease spread. The panel of identified proteinsmay play a role in spread of joint inflammation. With further validation,these putative prognostic biomarkers could improve the clinicalmanagement of patients

Irish Association of Rheumatology and Rehabilitation Proceeding of Meeting held at St Vincent’s Hospital on Friday 30th October, 1987

The incidence of bone and joint tuberculosis has fallen dramatically during the past thirty years in the Western World. In this hospital there were 29 cases of active tuberculosis of bone and joint diagnosed over a 10 years period (1977-87). The mean age of patients surveyed was 52.7 years (S.D.• and ranged from 17-87 years. 15 of the patients were female and 14 were male. The mean duration of symptoms prior to diagnosis was 9.8 months (S.D. • 7.9 months) and ranged f rom 2-~1t9 months. In this series there is a lower (33%) frequency of spinal involvement compared to other studies, in which spinal involvement accounts for 60% of cases. The most frequently involved joints were the knee (5), wrist (3) and hip (3). Other joints involved were ankles, elbows and a shoulder. Dorsal spine infection was present in 6 patients, lumbar spine in 4 patients, metarsal (3) and metacarpals (1). One patient had skeletal involvement of two sites at presentation ( lumbar spine and ankle). When they presented 5 of the patients had evidence of active lung disease, while 3 had evidence of active kidney disease. Many patients had no evidence on chest x-ray of previous T.B. Sedimentation rate and F.B.C. were completely normal in 6 patients. Tuberculosis should be considered as a possible cause for unexplained inflammatory arthritis at an early stage. The long duration of symptoms prior to diagnosis in this study indicates that this may not be the case. Early diagnosis of skeletal tuberculosis permits specific therapy with a reduction in morbidity and disability.