Rheumatoid Arthritis: Giani T

Simonini G, Giani T, Stagi S, de Martino M, Falcini F. · Department of Pediatrics-Rheumatology Unit, Via Pico della Mirandola 24, 50132 Florence, Italy. · Rheumatology (Oxford). · Pubmed #15741191 links to  free full text

Abstract: OBJECTIVE: To evaluate bone mineral status over 1 yr of etanercept treatment in juvenile idiopathic arthritis (JIA). METHODS: Twenty children (13 female, 7 male) aged 5.2-11.4 yr, with active polyarticular JIA were prospectively enrolled to receive etanercept (0.4 mg/kg, twice weekly). Responders were defined according to the American College of Rheumatology Pediatric 50 definition of improvement. Broadband ultrasound attenuation (BUA) by bone was determined at the left calcaneus to assess bone status at baseline and at 1-yr follow-up. RESULTS: After 12 months of treatment, 15 (75%) patients were considered as responders. At baseline, responders and non-responders did not differ with regard to age, disease duration, core-set variables or BUA and Z-score values (patient's value--age specific normal value/normal group's s.d.). At 6-month and 1-yr follow-up in the whole group, BUA and Z-score values were not significantly different compared with baseline. At 1-yr follow-up, but not at 6 months, all 15 responders, differently from non-responders, showed a significant increase in both BUA and Z-score values: BUA at 1 yr 55.2 +/- 3.3 vs baseline 43.5 +/- 3.2 dB/MHz, P<0.001; Z score at 1 yr -0.3 +/- 0.2 vs baseline 1.5 +/- 0.4, P<0.002. CONCLUSION: For the first time in childhood rheumatic disease this pilot prospective study, although in a small group, shows evidence that 1 yr of etanercept therapy by controlling the underlying disease activity induces a sustained benefit on JIA bone loss. Prospective studies in larger patient samples are needed to confirm these data.

Stagi S, Giani T, Simonini G, Falcini F. · Department of Paediatrics, University of Florence, Italy. · Rheumatology (Oxford). · Pubmed #15695302 links to  free full text

Abstract: OBJECTIVES: Autoimmune diseases have been associated with some organ non-specific rheumatological disorders such as rheumatoid arthritis and systemic lupus erythematosus; however, few studies have been performed in an extensive cohort of children with juvenile idiopathic arthritis (JIA). Our objective was to evaluate the thyroid function and the prevalence of antithyroid antibodies, autoimmune thyroiditis and coeliac disease in children with JIA. METHODS: One hundred and fifty-one children (120 female, 31 male, median age 8.3 yr, range 2.4-16.9 yr) with JIA were evaluated. All patients underwent thyroid function tests (u-TSH, free T(4) and free T(3)), antithyroglobulin (TgA) and antiperoxidase (TPOA) antibodies, antigliadin, anti-endomysium and antitransglutaminase antibodies. All patients with raised thyroid stimulating hormone levels, low thyroid hormone levels or positive TPOA and/or TgA values had a thyroid high-resolution sonography examination. Coeliac disease was confirmed by jejunal biopsy if the specific antibodies profile was positive. One hundred and fifty-eight age- and sex-matched Caucasian children from the same geographical area acted as controls. RESULTS: Fourteen (9.3%) patients showed subclinical hypothyroidism, 17 (11.9%) patients showed autoimmune thyroiditis with nine patients also showing a non-homogeneous thyroid parenchyma at ultrasound evaluation. Coeliac disease was demonstrated in 10 (6.6%) patients. Compared with controls, JIA patients had higher prevalence of subclinical hypothyroidism (P < 0.01), autoimmune thyroiditis (P < 0.0001) and coeliac disease (P < 0.005). CONCLUSIONS: JIA children have an increased prevalence of autoimmune thyroiditis, subclinical hypothyroidism and coeliac disease. These data seem to suggest careful monitoring of thyroid function, thyroid autoantibodies and coeliac disease in JIA children.

Masi L, Simonini G, Piscitelli E, Del Monte F, Giani T, Cimaz R, Vierucci S, Brandi ML, Falcini F. · Department of Internal Medicine, University of Florence, Florence, Italy. · J Rheumatol. · Pubmed #15124262 No free full text.

Abstract: OBJECTIVE: To evaluate serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kB-ligand (RANK-L) in patients with juvenile idiopathic arthritis (JIA); to correlate these values with disease activity variables, radiological bone damage, and bone mass; and to correlate OPG gene polymorphisms with bone mass. METHODS: Eighty-four patients (66 girls and 18 boys) with JIA and 40 sex and age-matched controls were enrolled. Serum OPG and RANK-L were measured using an enzyme-linked immunosorbent assay. OPG genotyping was performed by polymerase chain reaction. RESULTS: Patients with JIA had significantly higher levels of serum OPG than controls (p = 0.001) and lower levels of RANK-L in comparison with controls (p = 0.0003). The OPG/RANK-L ratio in patients was higher than in controls (p = 0.004). No significant correlations were found between disease duration, erythrocyte sedimentation rate, and C-reactive protein values with either OPG or RANK-L serum levels. A significant difference in serum OPG levels (but not in RANK-L) was found between patients with and without erosions (p = 0.008). No correlation was found between OPG and RANK-L levels and bone mass (DXA Z scores). A higher prevalence of OPG CC genotype was found in both patients (65.4%) and controls (82.5%) (p = 0.006). Subjects with CC genotype had a higher lumbar spine bone mineral density (LS-BMD). CONCLUSION: We evaluated for the first time levels of OPG and RANK-L in children with JIA. The higher OPG/RANK-L ratio in JIA might be the result of a compensatory production of OPG. The presence of the T allele of the OPG gene appears to be associated with low BMD.

Simonini G, Azzari C, Gelli AM, Giani T, Calabri GB, Leoncini G, Del Rosso A, Generini S, Cimaz R, Cerinic MM, Falcini F. · Rheumatology Unit, Department of Pediatrics, University of Florence, Via Pico della Mirandola 24, 50132 Florence, Italy. · Rheumatol Int. · Pubmed #14997340 No free full text.

Abstract: OBJECTIVE: Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid. METHODS: Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence. RESULTS: Circulating NEP levels were lower in JIA patients than in controls (42.0+/-16.6 vs 76.5+/-24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4+/-86.2 vs 40+/-15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6+/-5.2% vs 41.4+/-13%, P<0.001 and 18.1+/-7.5 vs 31.2+/-5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2+/-14.6% vs 9.1+/-2.4%, P<0.001 and 66.4+/-5.4 vs 22.8+/-14.7, P<0.001, respectively). CONCLUSIONS: The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzyme's role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation.

Falcini F, Vierucci S, Giani T, Cimaz R, Simonini G. · Department of Paediatrics-Rheumatology Unit, 50132 Florence, Italy. · Lancet. · Pubmed #14667747 No free full text.

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