Disease evolution in systemic juvenile idiopathic arthritis: an international, observational cohort study through JIRcohort.

BACKGROUND: Systemic juvenile idiopathic arthritis (systemic JIA) is a severe disease with both systemic and joint inflammation. This study aims to identify predictors of disease evolution within the systemic JIA population enrolled in the Juvenile Inflammatory Rheumatism cohort (JIRcohort). METHODS: Observational patient cohort study with 201 recruited children from 4 countries (3 European, 1 North Africa) from 2005 until 2019, using retrospectively (2005-2015) and prospectively (2015-2019) routine care collected data. RESULTS: Sixty-five patients with complete follow-up data for 24 months after first diagnosis were classified as monophasic (n = 23), polyphasic (n = 6) or persistent group (n = 36) corresponding to their evolution (unique flare, recurrent flares, or persistent disease activity respectively). The patients of the persistent group were more likely to have an earlier disease onset, before the age of 6 (OR 2.57, 95%-CI 0.70-9.46), persistence of arthritis at 12-months post-diagnosis (OR 4.45, 95%-CI 0.58-34.20) and higher use of synthetic DMARD (sDMARD, OR 5.28, 95%-CI 1.39-20.01). Other variables like global assessment by physician and by patient and C Reactive Protein levels at 12-months post-diagnosis were assessed but without any predictive value after adjusting for confounding factors. CONCLUSIONS: Our results suggest that the earlier disease onset, the persistence of arthritis throughout the first year of disease evolution and the need of sDMARD might predict a persistent disease course.

Hyperzincemia and hypercalprotectinemia: unsuccessful treatment with tacrolimus.

UNLABELLED: We report on a 5-year-old boy with hyperzincemia and hypercalprotectinemia. Treatment began with Tacrolimus at the age of 4 years and 6 months. Despite an initial correction of clinical and biological symptoms, zincemia and calprotectinemia progressively worsened with secondary reappearance of symptoms. CONCLUSION: Tacrolimus seems to have a transient effect in the treatment of Hyperzincemia and hyperprolactinemia.

[Ecchymotic angioedema revealing childhood systemic lupus erythematosus with anti-C1q antibodies]. / Angioedèmes à évolution ecchymotique révélant un lupus érythémateux systémique de l'enfant avec anticorps anti-C1q.

BACKGROUND: Hypocomplement urticarial vasculitis syndrome may be the presenting sign of systemic lupus erythematosus. Hypocomplement urticarial vasculitis presents as atypical urticaria associated in 50% of cases with angioedema. On laboratory investigation, hypocomplementaemia is the characteristic feature, with reduced C3, C4 and C1q. This disease is very rare in children. PATIENTS AND METHODS: An eight-year-old girl was hospitalised for relapsing urticaria with ecchymotic angioedema present for one year, in a setting of impaired general health and fever. Screening for native anti-DNA and antinuclear antibodies was positive. Analysis of complement revealed activation of the classical pathway with reduced CH50, C4 and C3. These anomalies persisted outside active episodes. The C1q fraction was completely depressed and screening for anti-C1q was positive. There was no quantitative or qualitative deficit in C1-esterase inhibitor. Direct immunofluorescence of skin lesions demonstrated deposits of immunoglobulin and complement. These episodes of angioedema persisted despite long-term systemic corticosteroid therapy (1mg/kg per day). DISCUSSION: This is the first reported case of hypocomplement urticarial vasculitis syndrome arising from systemic lupus erythematosus in a child exhibiting anti-C1q antibodies. Furthermore, this case is original because of the highly ecchymotic nature of the lesions. In the presence of angioedema with ecchymotic progression associated with atypical chronic urticaria, a diagnosis of hypocomplement urticarial vasculitis syndrome should be considered.

Interactions between biliary lipid micelles and intestinal brush border membranes investigated by 1H and 31P nuclear magnetic resonance.

The effect of taurocholate and lecithin-cholesterol-taurocholate mixed micelles on the structure of isolated intestinal brush border membranes was investigated by nuclear magnetic resonance (NMR). Rabbit brush border membranes isolated by a Mg2+ precipitation step were chosen for this study because of their stability and integrity as revealed by 31P NMR. Incubation of taurocholate with the brush border membranes does not induce significant solubilization of these membranes even when the taurocholate/phospholipid ratio reaches 3.0. 1H NMR studies indicate that taurocholate is included in the membrane bilayer at low concentration (3 mM). However this biliary salt produces a size diminution of the vesicles when its concentration increases. Incorporation of lecithin or lecithin-cholesterol in micelles of taurocholate and subsequent incubation with brush border membranes lead simultaneously to a decrease in the 31P NMR isotropic/bilayer line ratio, and to an increase in delta sigma. These results indicate a protective effect of these compounds against lytic damage of taurocholate. Furthermore the equilibrium distribution of lecithin between mixed micelles and the membrane bilayer is strongly in favour of complete integration of micellar components in the bilayer. These data suggest that uptake of lipids from the micellar phase by isolated brush border membranes involves an interaction of the micelles with membranes followed by a fusion process.

Molecular order, dynamics, and ionization state of phosphatidylethanolamine bilayers as studied by 15N NMR.

Dipalmitoylphosphatidylethanolamine (DPPE) and dipalmitoylphosphatidylcholine (DPPC), 15N-labeled in the polar head group, were synthesized. The proton-decoupled 15N spectra of DPPC and DPPE in aqueous dispersion have exactly the form anticipated for powder line shapes governed by an axially symmetric shielding tensor. The chemical shift anisotropy (delta sigma) of DPPC is lower than 0.4 ppm at 30 degrees C and vanished when the temperature or the half-height line width is increased; DPPE always exhibits an asymmetric line shape, and 15N NMR spectra of DPPE are obtained at various temperatures and simulated to measure exactly the chemical shift anisotropy. At each temperature, the order parameter of the C-N bond segment is derivated from delta sigma and reveals that the average orientation of the C-N bond around the axis of rotation is near the "magic angle" (54.7 degrees). Isotropic correlation times are derived from T1, which are higher than values obtained for phosphatidylcholine by other nuclei. Arrhenius plots of T1 and T2 allowed us to calculate the activation energy for the motion of the DPPE and the DPPC C-N bond. The value of this activation energy for the DPPE (53 kJ/mol) is higher than the one found for the DPPC C-N bond (32 kJ/mol). These differences agree with the capacity of the ethanolamine head groups to bind noncovalently to their neighbors in the plane of the membrane surface. A direct titration curve of the amino group is achieved by the variation of the chemical shift with the bulk pH, and the interfacial pKa is calculated to be 11.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of micellar lipids on rabbit intestinal brush-border membrane phospholipid bilayer integrity studied by 31P NMR.

The effect of biliary salts and fatty acids on the bilayer structure of rabbit intestinal brush-border membranes was studied using the nonperturbing probe 31P NMR. The broad, asymmetric lineshape of the 31P NMR spectrum of isolated brush-border vesicles demonstrates that their component phospholipids are organized in extended bilayers. These membranes are not significantly perturbed by incubation with physiological concentrations of biliary salts (3, 9, 18 mM), demonstrating that the vesicles are highly stable, corresponding to their biological function. However, the emergence of a narrow peak superimposed on the broad lineshape indicates that a small proportion of the membrane phospholipids has reached isotropic motion, which may correspond to external or internal micellar structures. Incubation with mixed micelles of fatty acids and taurochlorate show that long-chain fatty acids enhance the membrane-perturbing effect of taurocholate while short-chain, water-soluble fatty acids do not, suggesting a difference in the absorption mechanisms.

Cell surface modifications with trifluoromethyl dinitrophenyl-soluble protein conjugates: immunogenic role of noncovalently bound hapten.

Bovine serum albumin (BSA) was derivatized, under mild conditions, with trifluoromethyl-dinitrophenyl (CF3-DNP), a haptenic group cross-reacting with trinitrophenyl (TNP). High-field nuclear magnetic resonance of fluorine (19F-NMR) permitted to calculate the number of covalently and noncovalently bound haptenic groups per BSA molecule. Further dialysis against paratoluene sulfonic acid permitted to obtain CF3-DNP-BSA conjugates from which noncovalently bound hapten had been removed. Soluble conjugates containing 4 covalently bound plus 1 noncovalently bound hapten groups, or only 4 covalently bound groups, were added to splenocytes in culture. These splenocytes, after such treatments, were added to effector lymphocytes in a 5-day culture aimed at the generation of cytotoxic T lymphocytes (CTL) against the CF3-DNP-induced cell surface modification antigens. It was found that only the BSA conjugates that contained noncovalently bound haptens were able to generate CTL against target cells whose surface had been directly modified with CF3-DNP, whereas BSA bearing only covalently bound hapten groups were not. Replacing BSA by human serum albumin, or CF3-DNP by TNP, gave comparable results. Thus, under the conditions used, haptenic groups covalently bound to their soluble carrier protein did not generate hapten-dependent CTL, but noncovalently bound or free haptenic groups at very low concentration were able to do so.

[Visualization of different types of hapten-cell membrane interaction by fluorine high-field nuclear magnetic resonance]. / Visualisation, par résonance magnétique nucléaíre du fluor a haut-champ, de différents types d'interaction haptène-membrane cellulaire.

Using a high field spectrometer (5.9 Tesla) 19F-NMR spectrum of soluble material from 4 trifluoromethyl 2,6 dinitrobenzene sulphonate (CF3-DNBS) treated murine lymphocytes was recorded. CF3-DNBS is a fluorinated analog of 2,4,6 trinitrobenzene sulphonate (TNBS), and these compounds have been found to create cross-reacting antigenic modifications of cell surface. At least 4 distinguishable signals have been detected, and we think that 19F-NMR could be used to study, at a molecular level, some immunochemical problems concerning modification with TNBS.

Stored blood microfiltration. Evaluation of micro-aggregate filter composed of polyurethane foam and nylon wool.

Aggregates of amorphous material which develop during storage of banked blood have been implicated as a cause of pulmonary micro-embolism in man following massive transfusion. Such pulmonary micro-embolism may be a causal factor in the development of post traumatic pulmonary insufficiency. At present several microaggregate filters for use in massive transfusion are commercially available, and on of these is the Fenwal filter. It is composed of a screen filter which removes microclots of 250 microns and higher, a layer of polyurethane foam and a layer of nylon wool. The resistance of this device is very acceptable and the filter may be used for several blood units, but its efficiency seems less than that of Dacron wool filter.