Complement factor H (beta-1H globulin) is an important regulatory protein which inhibits the spontaneous complement activation via the alternative pathway. We describe a 15-year-old girl without any detectable factor H in plasma. She has had two episodes of meningococcal disease, but is otherwise completely healthy. Secondary to the factor-H deficiency, the levels of factor B, properdin, C3, and C5-C9 were strongly reduced due to spontaneous in vivo activation of the alternative complement pathway. Plasma C3dg was strongly elevated in spite of the factor-H deficiency; apparently erythrocyte CR1 substitutes for factor H in C3 degradation. Neither C3 nor complement lesions were demonstrable on her erythrocytes which did, however, show increased, spontaneous haemolysis in vitro in citrate plasma, but not in serum. The patient is a single child and her parents, who are unrelated and healthy, had half-normal levels of factor H. This reduction of factor H is sufficient to cause increased, spontaneous activation of the alternative pathway.

Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.

The possible pathogenic nature of the mutation is not clarified. We discuss the limitations of functional PSEN2 studies and the challenges associated with genetic counselling of family members at risk.

In this cross-sectional study, the circulating miRNA profile distinguished SLE patients with atherosclerosis from those without. Furthermore, an eight-miRNA signature was associated with thrombocytopenia, venous thrombotic events, and β-glycoprotein I antibodies in SLE patients. Prospective studies are needed to confirm the findings and to establish the precise role of circulating miRNA profiling in the evaluation of atherosclerosis in SLE.

BackgroundSLE patients have a marked increased risk of venous (VTE) and arterial (AT) thrombosis, which is not fully explained by traditional risk factors or the presence of anti-phospholipid antibodies. Thrombosis is a major cause of damage accrual, morbidity, and mortality in SLE. A better understanding of the pathogenesis and development of new biomarkers to identify patients at risk are needed. Recent studies link leptin and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) to subclinical atherosclerosis and galectin-3-binding protein (G3BP) to type I interferon activation and a pro-thrombotic environment.ObjectivesTo explore G3BP, interferon gamma-induced protein 10 (IP-10), soluble CD163 (sCD163), TWEAK, and leptin serum levels as predictors of venous and arterial thrombotic events, damage accrual, and all-cause mortality during long-term follow-up in a large cohort of Swedish SLE patients.MethodsBaseline clinical and paraclinical data including disease activity and damage scores (SLICC) were available from 167 SLE patients. VTE (deep vein thrombosis and/or pulmonary embolism) and AT (myocardial infarction and/or cerebrovascular incident) data were available with a median follow-up period of six years. Baseline serum G3BP, IP-10, sCD163, TWEAK, and leptin were quantified using ELISA. Univariate and multivariate analyses were conducted to asses associations between the serum biomarkers and the occurrence of VTE/AT, damage accrual, and death.ResultsIn the follow-up period 11 (7%) VTE and 12 (7%) AT events occurred. SLICC-scores increased in 79 (47%) patients, and 19 (11%) patients died. In the univariate Cox regression analysis G3BP levels were significantly associated with an increased risk of VTE (hazard ratio (HR) 1.10, 95% confidence interval (CI): 1.01–1.2, P=0.03). This persisted in the multivariate cox regression analyses when adjusting for age, gender, diabetes, antiphospholipid syndrome, and treatment with warfarin (HR 1.16, 95% CI: 1.04–1.31, P=0.01). None of the other serum biomarkers were associated with AT and VTE. No significant associations were observed between the biomarkers and changes in SLICC-scores or all-cause mortality.ConclusionsOur study identifies serum G3BP as a novel independent predictor of VTE in SLE. This may improve our understanding of VTE pathogenesis in SLE and aid future VTE risk stratification and prophylaxis. Further studies are needed to translate this into clinical practice.Disclosure of InterestNone declared

Comparison of the features of arthroscopic synovial biopsies with biopsy samples obtained at surgery

We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission. Acknowledgement: This research was supported by a European Commission (Acronym: EUROBANK, contract no: QOL-2000-14.1), web site http://www.ncl.ac.uk and by grant of 2nd Medical Faculty, Charles University in Prague, VZ no. 111300003. P2The significance of antibodies to cyclic citrullinated peptide, antikeratin antibodies, antiperinuclear factor, rheumatoid factor isotypes and HLA shared epitope in prediction of erosive disease in early rheumatoid arthritis patients J Vencovsky, L Sedova, S Machacek, J Gatterova, V Pesakova, J Kafkova and O Krystufkova Institute of Rheumatology, Prague, Czech RepublicObjectives: To evaluate a predictive value of autoantibody examinations in development of erosive disease in early rheumatoid arthritis (RA). Patients and methods: One hundred and fourteen patients with disease duration less than 2 years after the onset of symptoms were investigated. Only patients who fulfilled the diagnostic criteria for RA either at the beginning of the disease or during the follow-up period were included. The antibodies to cyclic citrullinated peptide (anti-CCP) (Immunoscan RA, Euro-diagnostica, The Netherlands), IgM, IgA and IgG rheumatoid factors (RF) were measured by ELISA, antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence, and the presence of HLA shared epitope (HLA SE) was detected by PCR with sequence specific primers. Patients were divided into two groups, either with erosive or non-erosive changes present on the hand or/and feet radiographs at the end of 24 months follow-up. Results: Seventy-six (66.7%) patients developed bony erosion, whereas 38 (33.3%) remained without destructive changes. The initial anti-CCP, AKA, APF, IgM RF, IgA RF, IgG RF ...