F Kanakoudi-Tsakalidou

The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis.

Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Thirty-one children (mean age:12.9+/-4.6 years) treated with anti-TNFs plus Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 32 age-matched children treated only with DMARDs were vaccinated with two doses of PCV7. After the first vaccine dose geometric mean titers (GMTs) were significantly increased for all vaccine serotypes (p<0.0001) in both groups and were found to be protective (>0.35microg/ml) in 87-100% of all children, depending on the serotype. Children receiving anti-TNFs achieved a significantly lower GMTs against serotypes 4, 14 and 23F (p<0.05). A >or=4-fold increase of the baseline titers to >or=5 vaccine serotypes was observed in 50% and 75% of the anti-TNF and control patients, respectively (p=0.0697). No patient developed vaccine-associated serious adverse events or disease flares.

Safety and efficacy of adalimumab treatment in Greek children with juvenile idiopathic arthritis

Objectives: To evaluate the safety and efficacy of adalimumab (AD) administration in patients with juvenile idiopathic arthritis (JIA). Methods: Twenty-six patients were enrolled from January 2004 to January 2008 in this prospective observational study. Inclusion criteria were either unresponsiveness to disease-modifying anti-rheumatic drugs (DMARDs; n = 17) or to other anti-tumour necrosis factor (anti-TNF) agents (n = 9) or development of uveitis under other anti-TNFs (n = 2 of the 9). Efficacy was estimated using the American College of Rheumatology Pediatric (ACR Pedi) criteria. Results: After 1–5 years of AD exposure, nine different adverse events (AEs) were recorded (12.6 AEs/100 patient-years), mainly mild respiratory tract infections and injection site-related reactions. Serious AEs (SAEs, 2.8/100 patient-years) were the development of abscess at the site of injection (n = 1) and lethal sepsis (n = 1). The ACR Pedi ≥ 30 responses for the first to the fifth year of treatment were 88.5, 57.7, 50.0, 34.6, and 11.5%, respectively. In total, 17 of the 26 (65.4%) patients responded to AD. Five of the 11 patients under steroids discontinued them 6 months post-treatment. Seven patients required weekly AD treatment to maintain remission and four of them benefited from this policy. Recurrent uveitis was hindered in three of the six patients, no new cases were recorded, and radiological regression was observed in two of the four patients with lesions. Conclusions: AD was safe and efficacious during the study period in the majority of patients. However, vigilance is required for the early detection of severe and potentially fatal infections. AD may control recurrent uveitis and radiological progression.

Persistent or Severe Course of Reactive Arthritis Following Salmonella enteritidis Infection: A prospective study of 9 cases

During a 7 year-period 9 children (7 boys, 2 girls) with juvenile reactive arthritis (JReA) due to Salmonella enteritidis (Se) were prospectively studied because of an unusual type of onset and/or course of the disease. The mean duration of JReA activity was 9 +/- 3.6 months. The mean follow-up time was 55.2 +/- 17.4 months. JReA presented as any of the three types of juvenile chronic arthritis (JCA), namely, as asymmetrical oligoarthritis, polyarthritis, or systemic JCA in 5, 2, and 2 patients respectively. Two patients had pericarditis and three developed the complete or incomplete Reiters syndrome during the disease or during a recurrence. Five patients carried the HLA-B27 and 3/5 developed psoriatic lesions 1 to 15 months after the onset of JReA. The presence of HLA-B27 and psoriasis was associated with a more prolonged course of JReA. However, no patient developed late radiological lesions or sacroiliitis during follow-up.

Simultaneous changes in serum HMGB1 and IFN-α levels and in LAIR-1 expression on plasmatoid dendritic cells of patients with juvenile SLE.. New therapeutic options?

We investigated the simultaneous changes in serum levels of HMGB1 and IFN-α as well as in LAIR-1 expression on plasmatoid dendritic cells (pDCs) of juvenile systemic lupus erythematosus (jSLE) patients in order to explore their involvement in the disease pathogenesis and their correlation with disease activity and other characteristics. In total, 62 blood samples were studied from 26 jSLE patients (18 girls), aged 8–16 years. Twenty healthy subjects (16 girls) of comparable age were included as healthy controls (HCs). Concentrations of serum HMGB1 and IFN-α were assessed by ELISA and LAIR-1 expression on pDCs by five-color flow cytometry. The disease activity index was assessed by SLEDAI and ECLAM scores. It was found that mean serum levels both of HMGB1 and IFN-α were significantly increased in jSLE patients compared to HCs and in jSLE patients with active disease with or without active nephritis compared to those with inactive disease. Mean serum levels of HMGB1 were positively correlated with levels of IFN-α and both were positively correlated with the SLEDAI and ECLAM scores. The expression of LAIR -1 on pDCs of jSLE patients was significantly lower than that of HCs. In conclusion, our findings indicate that serum HMGB1 not only represents a potential marker of disease activity but together with the lack of LAIR-1 inhibitory function may contribute to the sustained inflammatory action of IFN-α in jSLE. In this regard, blocking the action of HMGB1 and its receptors or enhancing the expression/inhibitory function of LAIR-1 on pDCs should be included in future immune interventions for controlling jSLE.

Ghrelin levels in patients with juvenile idiopathic arthritis: relation to anti-tumor necrosis factor treatment and disease activity

Studies in adults with rheumatoid arthritis reported low serum ghrelin that increased following anti-tumor necrosis factor (TNF) infusion. Data on juvenile idiopathic arthritis (JIA) are lacking. The aim of this pilot study was to explore serum ghrelin levels in patients with JIA and the possible association with anti-TNF treatment, disease activity, and nutritional status. Fifty-two patients with JIA (14/52 on anti-TNF treatment) were studied. Juvenile idiopathic arthritis was inactive in 3 of 14 anti-TNF-treated patients and in 11 of 38 non-anti-TNF-treated patients. The nutritional status, energy intake/requirements, appetite, and fasting serum ghrelin levels were assessed. Ghrelin control values were obtained from 50 individuals with minor illness matched for age, sex, and body mass index. Ghrelin levels in patients with JIA were significantly lower than in controls (P < .001, confidence interval [CI] = -101 to -331). Analysis according to anti-TNF treatment and disease activity showed that ghrelin levels were comparable to control values only in 3 patients with anti-TNF-induced remission. Ghrelin in non-anti-TNF-treated patients in remission was low. Multiple regression analysis showed that disease activity (P = .002, CI = -84.16 to -20.01) and anti-TNF treatment (P = .003, CI = -82.51 to -18.33) were significant independent predictors of ghrelin after adjusting for other potential confounders. Ghrelin did not correlate with nutritional status, energy balance, and appetite. Serum ghrelin is low in patients with JIA and is restored to values similar to those in controls following anti-TNF-induced remission. Our study provides evidence that TNF blockade is independently associated with serum ghrelin, which possibly contributes to anti-TNF-induced remission. These preliminary results could form the basis for future research.

Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis

The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will facilitate the non‐invasive diagnosis, follow‐up and more appropriate use of treatment. The aim of this study was to explore the role of serum high‐mobility group box 1 (HMGB1) protein, antibodies against nucleosomes (anti‐NCS), complement factor C1q (anti‐C1q) and glomerular basement membrane (anti‐GBM) in pLN. Serum samples of 42 patients with paediatric systemic lupus erythematosus (pSLE) (22 with pLN and 20 without renal involvement), 15 patients with other autoimmune nephritis (AN) and 26 healthy controls (HCs) were examined using enzyme‐linked immunosorbent assay (ELISA). The activity of both pSLE and pLN was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) tool. The levels of all four biomarkers were significantly higher in pLN compared to AN and to HCs. The anti‐NCS, anti‐GBM and HMGB1 serum levels were significantly higher in pLN than in pSLE without renal involvement. The anti‐C1q and the HMGB1 serum levels were correlated positively with pSLE activity. The HMGB1 serum levels were also correlated positively with pLN activity. These findings suggest that serum anti‐NCS, anti‐GBM and HMGB1 may serve as biomarkers specific for the presence of nephritis in pSLE. HMGB1 emerged as a useful biomarker for the assessment of pLN and pSLE activity, whereas anti‐C1q only of pSLE activity.

The use of Etanercept and Adalimumab in the management of JIA: a 5-year follow-up study

Results Safety: Common respiratory tract infections were recorded in 28% of pts (10/34 under ET and 3/14 under AD). Serious infections were recorded in 4.7% (1 ET, 1 AD). No other serious adverse effects were recorded. Efficacy: ACRped 50–70. 1 st yr: 88% of the ET and 68% of the AD group. 2 nd yr: 81% of the ET and 66.7% of the AD group. 3 yr: 83% of the ET and 100% of the AD group. During the 5-yr period, 11/46 pts (28%) switched from ET to AD or vice versa. Of all patients, 32.5% discontinued anti-TNF treatment due to remission and 52.2% had a satisfactory response (ACRped 50–70), while 8.7% had a poor response either to ET or AD. Conclusion Most of the patients with refractory to conventional treatment JIA respond satisfactorily to the long-term administration of anti-TNFs. The first 2 years are critical to predict a good and sustained response. Although serious infections are rare, a systematic vigilance is warranted in order to avoid fatal outcomes. from 15th Paediatric Rheumatology European Society (PreS) Congress London, UK. 14–17 September 2008

The portrait of Familial Mediterranean Fever in N. Greek pediatric patients: a 30-year experience

Familial Mediterranean Fever (FMF), is the second commonest autoinflammatory disease in pediatric Greek patients (pts) after PFAPA. So far, long-term follow-up case series in Greek FMF pts have not been emerged.

AB1011 Synovial Fluid Biomarkers, Prognostic for the Course of Juvenile Idiopathic Arthritis: A Decade's Follow-Up Study

Background The course and outcome of oligo-JIA is more or less unpredictable. So far, no internationally acceptable prognostic biomarkers, regarding the progression of oligo- to the extended disease type have been defined. Objectives The aim of this study was to assess the immunophenotype plus cytokine profile in synovial fluid (SF) of patients (pts) with JIA and to evaluate the findings in respect to the severity of the disease course in order to define those pts who need early aggressive treatment. Methods 73 SF samples from the knees of 57 JIA patients (F: 48, median age 11.49 yrs) were studied. 20/57 pts had oligo-persistent (O-per), 27 oligo-extended (O-ext) and 10 polyarthritis (poly). 25 age-matched children (25 SF samples) with recent traumatic knee arthritis served as controls. The SF immunophenotype and cytokine levels were assessed by flow cytometry and ELISA respectively. Results The median CD4:CD8 T cell ratio was found to be significantly lower in 19/57 pts (24/73 samples) from all 3 JIA pt groups as compared to the controls (0.75 vs 1.55, p<0.01). Also, the median CD4:CD8 ratio was significantly lower in the O-ext disease type (0.70) as compared to O-per and poly (1.54 and 1.57 respectively p<0.01). 23/24 SF samples with a low (<0.8) ratio had a polyarticular disease course (21 O-ext, 3/10 poly). Tregs were significantly lower and Th17 significantly higher in all 3 JIA pt groups as compared to the controls (p<0.001), especially in O-ext. Cytokines IL-17, IL-23 and IL-6 were significantly higher in all JIA pt groups as compared to the controls. A positive correlation between low CD4:CD8 ratio and the disease duration as well as, values of Th17 cells, IL-17 and IL-23 levels were found regardless of the JIA subtype. Conclusions A low ratio of CD4:CD8 T cells in combination with high levels of IL-17 and IL-23 in SF of JIA pts can predict a prolonged, polyarticular course of the disease and may be used as “the window of opportunity” for a more targeted treatment. References Hunter PJ, et al. Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression. Arthritis Rheum 2010;62: 896-907. Disclosure of Interest None declared

PReS-FINAL-2299: Novel biomarkers for the assessment of pediatric systemic lupus erythematosus nephritis (preliminary report)

Results The pSLE nephritis patients had significantly higher serum levels of anti-NCS [median: 48.89 (IQR: 31.4880.81) U/ml versus 12.5 (11.5-27.8) U/ml, p < 0.001], anti-C1q [22.75 (12.77-56.4) U/ml versus 12.5 (12.512.5) U/ml, p < 0.001], anti-GBM [3.88 (2.25-6.94) U/ml versus 2.2 (2.2-2.4) U/ml, p = 0.002] and HMGB1 [9.9 (5.7-32.23) ng/ml versus 2.5 (2.5-2.5) ng/ml, p < 0,001], than the patients with nephritis of other causality. Serum anti-GBM levels were significantly higher in the pSLE nephritis patients compared to the pSLE patients without nephritis [3.88 (2.25-6.94) U/ml versus 2.25 (2.2-2.83) U/ml, p = 0.014], while this was not true for the rest of the biomarkers. In the pSLE nephritis patients no correlation was found between serum antiGBM levels and pSLE nephritis disease activity. Serum anti-NCS and anti-C1q levels were positively correlated with the ECLAM score in the pSLE patients as a whole (p = 0.002, rho = 0.492 and p = 0.007, rho = 0.461, respectively). Conclusion In this pure Caucasian Northern Greek pSLE population, high serum anti-GBM levels were found to be associated with the presence of nephritis, but not with the nephritis disease activity. Serum anti-GBM, anti-NCS, anti-C1q and HMGB1 may be used to differentiate patients with pSLE nephritis from patients with nephritis of other causality. Furthermore, serum anti-NCS and anti-C1q may be useful for the estimation of pSLE disease activity.