Iea Hoffman

Juvenile-onset systemic lupus erythematosus: different clinical and serological pattern than adult-onset systemic lupus erythematosus

Objective: To investigate differences in clinical signs and symptoms, and in antinuclear antibodies (ANA), between patients with juvenile-onset and adult-onset systemic lupus erythematosus (SLE). Methods: Clinical and serological data of 56 patients with juvenile-onset SLE were compared with data of 194 patients with adult-onset SLE. ANA were determined by line immunoassay and by indirect immunofluorescence on Crithidia luciliae. Results: Renal involvement, encephalopathy and haemolytic anaemia were seen, and anti-dsDNA, anti-ribosomal P and antihistone antibodies found, significantly more often in juvenile-onset SLE. Anti-dsDNA antibodies were directly associated, and anti-ribosomal P antibodies inversely associated, with renal involvement in juvenile-onset SLE. In juvenile patients with SLE and anti-dsDNA and without anti-ribosomal P antibodies the odds ratio for glomerulonephritis was 9.00; no patients with anti-ribosomal P but without anti-dsDNA had renal involvement. Conclusion: Patients with juvenile-onset SLE more often have renal involvement and encephalopathy than patients with adult-onset SLE. Anti-ribosomal P, anti-dsDNA and antihistone antibodies are more often found in patients with juvenile-onset SLE.

CARD15 polymorphisms are associated with anti-Saccharomyces cerevisiae antibodies in caucasian Crohn's disease patients

Carriage of CARD15 gene polymorphisms and the serological marker anti‐Saccharomyces cerevisiae antibodies (ASCA) are two markers for Crohns disease (CD). Similar phenotypes have been associated with both markers. In the present study we analysed whether both markers were associated with each other and, if so, whether this association could be explained by a direct link or by an indirect association with those phenotypes. Therefore, we included 156 consecutive Caucasian CD patients and assessed the prevalence of the three common single nucleotide polymorphisms in the CARD15 gene. Serum samples were analysed for IgA and IgG ASCA by ELISA. CD patients with CARD15 polymorphisms were more frequently ASCA positive (OR 2·7 (1.4–5.2); P = 0·002) and had higher titres for ASCA IgA (P = 0·005) and ASCA IgG (P < 0·001) compared to patients carrying the wild type polymorphisms. Multivariate analysis demonstrated that this association was independent from ileal disease, penetrating disease and stricturing disease, the need for resective bowel surgery, familial cases, smoking habits and early age at onset. Homozygotes or compound heterozygotes for CARD15 polymorphisms had significantly more frequent ASCA positivity compared to single heterozygotes (OR 9·1 (1.1–74.2), Pc (corrected P‐value) = 0·030). These data indicate that there is a significant association between the carriage of CARD15 polymorphisms and ASCA, independent of the described phenotypes. Moreover, ASCA positivity is more frequent in CD patients carrying 2 CARD15 polymorphisms compared to single heterozygotes.

Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory autoimmune arthritis

Objectives: Improved DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology was used to monitor the changes in the galactosylation status of serum immunoglobulins during the immune response and therapy of autoimmune arthritis. Methods: Collagen-induced arthritis (CIA) was induced in susceptible DBA/1 mice and the undergalactosylation status (UGS) of serum immunoglobulins was determined using the improved DSA-FACE technology. Prophylactic intravenous tolerisation with type II collagen as well as semitherapeutic treatment with dexamethasone (DEX) were performed and UGS was analysed. Next, the serum immunoglobulin glycosylation profiles of patients with rheumatoid arthritis (RA) and spondyloarthropathy (SpA) were studied and changes in the UGS scores during anti-tumour necrosis factor (TNF)α therapy followed. Results: In the longitudinal CIA study, the undergalactosylation state of immunoglobulins was found to be significantly correlated with the clinical arthritis scores. Upon collagen-specific tolerisation as well as glucocorticoid semitherapeutic treatment, improvement of the clinical arthritis scores correlated with decreased levels of UGS. It was also demonstrated that withdrawal of DEX was associated with an increased UGS score. Interestingly, reversibility in the UGS was also shown during treatment of patients with RA and SpA with anti-TNFα. Conclusions: These findings demonstrate that the UGS of serum immunoglobulins changes during the disease course of CIA and that this UGS is inhibited by antigen-specific and antigen-independent treatment procedures. The observation that Ig galactosylation is a reversible process is also documented during treatment of patients with RA and SpA with anti-TNFα.

History and diagnostic value of antibodies to citrullinated proteins in rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory joint disease characterized by the presence of autoantibodies. The best known autoantibody is the rheumatoid factor. Another group of antibodies directed against citrullinated epitopes is proven to be more specific for rheumatoid arthritis. This review gives an overview of the history of the different anti-citrullinated protein antibody detection methods and their diagnostic and prognostic properties in RA.

Prediction of arthritis using a modified Kohonen mapping and case based reasoning

Abstract Rheumatoid arthritis and spondyloarthropathy are the two most frequent forms of chronic autoimmune arthritis. These diseases lead to important inflammatory symptoms resulting in an important functional impairment. In this paper we apply a topological mapping combined with a case based reasoning evaluation criterion to predict early arthritis. The first part presents a brief introduction to the problem and self-learning neural networks while the second part of this paper will apply this technique together with a case based reasoning evaluation criterion to diagnostic classification. Finally the paper shows that the Kohonen neural network achieves good performance that exceeds the results of other neural network approaches and decision trees.

P236 Disease severity after 3 years of treating newly diagnosed pediatric Crohn's disease patients (the BELCRO cohort)

Background: In IBD, primary sclerosing cholangitis (PSC) confers an increased risk of colorectal neoplasia (CRN). The aim of this study was to evaluate the effect of liver transplantation (LT) on development of CRN in patients with PSC and IBD. Methods: From our LT cohort (n = 275, period 1992 2011), 21 patients were identified with PSC and IBD and a follow-up post LT >6 months (PSC+LT). We further identified 39 patients with PSC and IBD without LT (PSC). In these patients with PSC and IBD, we performed a Cox regression analysis with LT as a timedependent covariate. We additionally compared development of CRN after LT between patients with PSC and IBD and the non-PSC LT population. To this end, we compared PSC+LT to a group of LT patients without PSC or IBD that was matched for sex, age and duration of post LT follow up (LT). Results: In patients with PSC, LT increased the risk of CRN in PSC patients with IBD in the univariate analysis; this effect was no longer present in the multivariate analysis. Cumulative incidence of CRN was 29% in the PSC+LT group vs. 10% in the PSC group (ns). CRN-free survival did not differ between PSC+LT and LT groups. Cumulative incidence of CRN for the groups was similar (resp. 29% vs. 32%, ns). Conclusions: Liver transplantation did not increase the rate of CRN in patients with both PSC and IBD. Furthermore, the rate of development of CRN did not differ between PSC+LT patients and the general LT population.

P550 Diagnosing and treating pediatric Crohn's disease patients: is there a difference between adult and pediatric gastroenterologists’ practices? Results of the BELCRO cohort

(1) Pediatric Gastroenterology, Queen Paola children’s hospital, Antwerp, Belgium; (2) Pediatric Gastroenterology, UZB, Brussels, Belgium ; (3) Systems and Modeling Unit, Montefiore Institute, ULG, Liege, Belgium ; (4) Bioinformatics and Modeling, GIGA-R, ULG, Liege, Belgium ; (5) Pediatric Gastroenterology, Universite catholique de Louvain, Cliniques universitaires St Luc, Brussels, Belgium; (6) Pediatric Gastroenterology, UZ Gent, Belgium.

Presence of anti-RNP-A and anti-RNP-C antibodies is inversely associated with renal symptoms of systemic lupus erythematosus

1 Rheumatoid arthritis — class prediction by autoreactivity profiles R Bergholz1, F Schumann1, S Behrens1, U Ungethüm1, G Valet2, WA Schmidt3, GR Burmester1, JM Engel4, WJ van Venrooij5, G Steiner6, S Bläß1 1Department of Rheumatology & Clinical Immunology, Charité University Clinic, Berlin, Germany 2MPI Biochemistry, Munich, Germany 3Clinic for Rheumatology Berlin Buch, Berlin, Germany 4Rheumaklinik, Bad Liebenwerda, Germany 5Department of Biochemistry, University of Nijmegen, The Netherlands 6Divison of Rhematology, Department Internal Medicine III, Vienna General Hospital, Austria Arthritis Res Ther 2003, 5 (suppl 1):1