Anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis.

The objectives were to determine the prevalence and clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with juvenile idiopathic arthritis (JIA). Anti-CCP antibodies were checked by ELISA in 68 children with JIA, 38 males and 30 females with mean age of 10.6 (+/-4.02) years and disease duration of 3.7 (+/-1.8) years. Thirty-eight (56%) patients had polyarticular disease, 20 (29%) patients had oligoarticular disease and 10 (15%) patients had systemic onset disease. All patients had their antinuclear antibodies (ANA), rheumatoid factor (RF) and ESR checked and x-rays performed to look for erosions. Results were compared to those of 20 healthy children, 14 children with juvenile systemic lupus erythematosus (JSLE) and 30 adults with rheumatoid arthritis (RA). Anti-CCP antibodies were positive in 14/68 (20.6%) patients with JIA, all had polyarticular-onset disease. All patients with positive anti-CCP antibodies had RF-positive polyarthritis. Anti-CCP antibodies were negative in all patients with oligoarticular-onset and systemic-onset disease including 2 patients with extended oligoarthritis. Anti-CCP antibodies were negative in healthy and JSLE controls but were positive in 20/30 (66.5%) adults with RA. Anti-CCP antibodies correlated significantly with joint erosions in patients with JIA (p = 0.004) but no significant relation was found between anti-CCP antibodies and ANA positivity or raised ESR. These data confirm that anti-CCP antibodies are less prevalent in JIA than adult RA but are detectable in a significant proportion of RF-positive patients with polyarticular-onset JIA. The current study showed significant relation between anti-CCP positivity and erosive joint disease in JIA.

Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis.

OBJECTIVES: Dose-dependant gastrointestinal and cardiovascular side-effects limit the use of NSAIDs in the management of RA. The n-3 essential fatty acids (EFAs) have previously demonstrated some anti-inflammatory and NSAID-sparing properties. The objective of this study was to determine whether cod liver oil supplementation helps reduce daily NSAID requirement of patients with RA. METHODS: Dual-centre, double-blind placebo-controlled randomized study of 9 months' duration. Ninety-seven patients with RA were randomized to take either 10 g of cod liver oil containing 2.2 g of n-3 EFAs or air-filled identical placebo capsules. Documentation of NSAID daily requirement, clinical and laboratory parameters of RA disease activity and safety checks were done at 0, 4, 12, 24 and 36 weeks. At 12 weeks, patients were instructed to gradually reduce, and if possible, stop their NSAID intake. Relative reduction of daily NSAID requirement by >30% after 9 months was the primary outcome measure. RESULTS: Fifty-eight patients (60%) completed the study. Out of 49 patients 19 (39%) in the cod liver oil group and out of 48 patients 5 (10%) in the placebo group were able to reduce their daily NSAID requirement by >30% (P = 0.002, chi-squared test). No differences between the groups were observed in the clinical parameters of RA disease activity or in the side-effects observed. CONCLUSIONS: This study suggests that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA patients.

Transforming growth factor beta 1 in children with systemic lupus erythematosus: a possible relation with clinical presentation of lupus nephritis.

Plasma and urinary (latent and active) TGF-beta1 levels were assessed in 32 children with active lupus and compared to 15 healthy controls of matched age and sex. Plasma latent and active TGF-beta1 levels in children with active disease were significantly lower than controls (P = 0.004 and P < 0.001 respectively). Plasma active TGF-beta1 correlated negatively with Systemic Lupus Erythematosus Disease Activity Index (r = -0.38, P = 0.03). On the contrary, urinary latent and active TGF-beta1 levels in children with active disease were significantly higher than controls (P < 0.001 and P = 0.003 respectively). Urinary active TGF-beta1 levels correlated positively with Anti-ds DNA titre (r = 0.42, P = 0.015) and negatively with serum C3 levels (r = -0.48, P = 0.005). Patients with symptomatic nephritis had significantly elevated urinary active TGF-beta1 levels in comparison to those with silent nephritis (P = 0.008). From this data we conclude that lowered plasma TGF-beta1 levels may be a feature of systemic immune dysfunction in children with active lupus while increased renal production of active TGF-beta1 seems to have a role in the clinical presentation of lupus nephritis.

Effect of sperm viability, plasmalemma integrity, and capacitation on patterns of expression of mannose-binding sites on human sperm.

The objective of this study was to characterize patterns of surface expression of mannose-binding sites (MBS) on human spermatozoa while evaluating the influence of sperm viability, plasma membrane integrity, and capacitation, D-Mannose binding sites were visualized by fluorescence microscopy using fluoresceinated mannose-enriched bovine serum albumin (FITC-DMA). To verify the probe specificity, 200 mM D-mannose and D-mannosylated albumin 200 micrograms/mL (DMA) were used as competitive inhibitors. Fluoresceinated bovine serum albumin (FITC-BSA) was used as control. Sperm membrane integrity was checked with a hypoosmotic swelling test (HOST) and sperm viability with Hoechst 33,258 at 1 microgram/mL. Viable spermatozoa with intact plasma membrane presented two main patterns: light bar (weak labeling of the equatorial segment) and slot (labeling of the pre- and postequatorial areas with a negative band in between). These patterns were significantly inhibited when unlabeled D-mannose or DMA were included in the medium. The percentages of spermatozoa displaying these two patterns increases significantly during capacitation. Nonviable spermatozoa with altered plasma membrane integrity presented multiple fluorescent patterns, all of which were present when FITC-BSA was used as the marker. None of them could be suppressed by unlabeled D-mannose or DMA. Viable spermatozoa displayed two main patterns which increased their incidence with capacitation and may be the only specific patterns for surface MBS. Other patterns detected in spermatozoa bearing altered plasma membranes may be due to nonspecific BSA binding or intracellular MBS recognition.

Mannose-binding sites on human spermatozoa and sperm morphology.

OBJECTIVE: To verify a possible association between the expression of sperm head mannose-binding sites and sperm morphology. DESIGN: Prospective in vitro study. SETTING: University-based sperm biology and andrology laboratories. PARTICIPANTS: Twenty-seven fertile donors and 45 patients consulting for infertility. INTERVENTIONS: D-mannose-binding sites were identified using a fluoresceinated mannose-enriched bovine serum albumin. Hoechst 33258 was included to confirm sperm viability and hypo-osmotic swelling test to assess plasma membrane integrity. Sperm morphology was judged by strict criteria and semen samples were classified into three groups: normal (group N, > 10% morphologically normal sperm, n = 27), good prognosis (group G, 5% to 10%, n = 23), or poor prognosis (group P, < or = 4%, n = 22). RESULTS: Only viable (Hoechst 33258 negative) spermatozoa with intact plasma membrane (hypo-osmotic swelling test positive)were considered in the evaluation of mannose-binding sites. The incidence of spermatozoa showing surface mannose-binding sites was higher in the N group (48.1% +/- 1.9%; mean +/- SEM) then in the G (17.6% +/- 4.4%) or P (7.6% +/- 2.3%) groups. Total mannose-binding site expression and percentage of morphologically normal sperm showed a high positive correlation (r = 0.80). CONCLUSION: Altered expression of mannose-binding sites, putative zona receptors, may be one of the molecular defects causing decreased fertility in morphologically abnormal human sperm.