Autoantibodies against P29ING4 are associated with complex regional pain syndrome

Introduction!#!Complex regional pain syndrome (CRPS) is a complication following trauma or surgery and may be difficult to diagnose since biomarkers are lacking. Using protein array technology, we found antibodies binding to p29ING4, which we further characterized using ELISA.!##!Methods!#!Thirty-six sera of early-stage type 1 CRPS, 66 sera of rheumatoid arthritis (RA), 53 sera of axial spondyloarthritis (axSpA), 29 sera of psoriatic arthritis (PsA), 22 sera of patients after radial fractures (trauma control), and 100 sera of blood donors (BD) were analyzed for anti-p29ING4. We established ELISAs with 7 different antigens and using different secondary antibodies binding to IgG, IgG1, IgG2, IgG3, IgG4, IgA, and IgM, and 2 different tests to detect immune complexes (IC) of p29ING4 and IgG or IgG1.!##!Results!#!The highest likelihood ratios versus CRPS and trauma control were observed considering the A1-23 (sensitivity 19%, specificity 100%, LR > 19) using IgG as a secondary antibody, the A120-165 (sensitivity 17%, specificity 100%, LR = 17) using IgG as a secondary antibody and the A120-165 (sensitivity 31%, specificity 95%, LR = 6.2) using IgA as a secondary antibody. IC of p29ING4 and IgG were present in 11/36 (31%) CRPS sera, 17/64 (27%) RA sera, 13/53 (25%) SpA sera, 5/29 (17%) PsA sera, 1/22 (5%) trauma control sera, and 4/100 (4%) sera of BD. IC of p29ING4 and IgG1 were present in 14/36 (39%) CRPS sera, 19/64 (30%) RA sera, 13/53 (25%) SpA, 1/29 (3%) PsA, 2/22 (9%) trauma control, and 4/100 (4%) of the BD sera.!##!Conclusion!#!Due to the lack of other biomarkers of type 1 CRPS, P29ING4 autoantibodies could be helpful in its diagnostic work-up

Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis

We previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF). Methods mRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients. NGF was also determined in synovial tissue (ST) biopsies of 10 RA and 10 SpA patients. The production of NGF by monocytes and lymphocytes was assessed by flow cytometry of SF cells, synovial tissue derived fibroblast-like synoviocytes (FLS) were assessed by ELISA on culture supernatant. Results SF cell analysis revealed a clear BDNF and NGF mRNA expression, with significantly higher NGF expression in RA and SpA patients than in the OA group. NGF expression was higher in ST samples of RA as compared to SpA. Using intracellular FACS analysis, we could demonstrate the presence of the NGF protein in the two inflammatory arthritis groups on both CD3+ T lymphocytes and CD14+ cells, i.e. monocytes/macrophages, whereas cultured FLS did not produce NGF in vitro. Conclusions Neurotrophins and especially NGF are expressed in the synovial fluid and tissue of patients with peripheral synovitis. The presence of neurotrophins as well as their receptors, in particular the NGF/trkA-p75 axis in peripheral synovitis warrants further functional investigation of their active involvement in chronic inflammatory arthriti

Widespread use of pure and impure placebo interventions by GPs in Germany

Aim. To collect data on the use of placebo interventions by GPs in Germany. Methods. A questionnaire was mailed to 400 randomly selected GPs in Bavaria. Non-responders were reminded by telephone after 4 weeks and were given a second copy of the questionnaire after a further 3 weeks. Results. In all, 208 completed questionnaires were returned. The majority of GPs (88%) have used a placebo at least once in their practice; 45% have used pure placebos, such as saline injections and sugar pills, at least once last year; the median frequency of use was 5 [interquartile range (IQR), 2–10]. The use of impure placebos during the past year was more common: 76% of GPs have used impure placebos, i.e. medical interventions that have pharmacological or physical activity but have no intrinsic effect (e.g. pharmacological or physical action) on the patient's disease or its symptoms, with a median frequency of 20 times per year (IQR, 10–50). The main reason for the use of placebo was a possible psychological effect, followed by the expectation of patients to receive a treatment. For the majority of GPs placebo interventions were ethically justified if they were used for a possible psychological effect. Conclusions. Placebo interventions are a widely accepted part of medical treatment in German general practices and are used primarily for their psychological effects. Impure placebos are used much more frequently than pure placebos