Antinuclear antibodies positivity is not rare during multiple sclerosis and is associated with relapsing status and IgG oligoclonal bands positivity.

INTRODUCTION: As an immune-mediated disease of the central nervous system, multifaceted aspects of a humoral immune response are widely described during multiple sclerosis (MS). However, the prevalence of different auto-antibodies, such as antinuclear antibodies (ANA), during MS is very variable and their clinical relevance remains controversial. Our aim was to evaluate the prevalence and clinical correlations of ANA positivity in South Tunisian MS patients. MATERIAL AND METHODS: We performed ANA screening using indirect immunofluorescence (IIF) on HEp-2 cells (Biosystems®) in 82 MS patients. For ANA positive samples (titer ≥1/160), anti-ds-DNA detection (IIF on Crithidia luciliae (Biosystems®)) and extractable nuclear antigen typing (immunodot (Euroimmun®)) were performed. RESULTS: ANA were positive in 35/82 MS patients (42.7%). The titer was ≥1/320 in 16/35 patients. The antigenic specificity of ANA was identified in 7/35 patients. None of the patients had extra-neurological manifestations. No correlation was found between ANA and age, gender, MS course, disease duration, disability, annual relapse rate nor IgG index. ANA positivity was more frequent in patients with IgG oligoclonal bands (OCB) (47.1%) than in patients without IgG OCB (16,6%) (p=0.049). Regarding disease activity, ANA positivity was significantly more frequent in patients with relapse (52.6%) than in patients in remission (25.9%) (p=0.031). CONCLUSION: Our results showed that ANA positivity in MS disease is not rare. This positivity was not associated with clinical expression of any connective tissue disease. ANA occurrence in MS was associated with IgG OCB+ profile and relapsing status, probably reflecting an ongoing immune dysregulation.

Plasma oxysterol profiling in children reveals 24-hydroxycholesterol as a potential marker for Autism Spectrum Disorders.

Cholesterol and its oxygenated metabolites, such as oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorder. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, X-linked adrenoleukodystrophy, and Smith-Lemli-Opitz Syndrome. Recent studies have shown that Autism Spectrum Disorders are associated with disruption of cholesterol metabolism. The present study aimed at investigating the profile of oxysterols in plasma and their association with clinical parameters in patients with Autism Spectrum Disorders. Thirty-six children with Autism Spectrum Disorders and thirty-eight healthy children, from Sfax (a southern area of Tunisia) matched for age and sex, were included in the study. The severity of Autism Spectrum Disorders was evaluated using the childhood autism rating scale. Standard lipid profile (total cholesterol, triglycerides, and high-density lipoprotein-cholesterol), serum glucose, high-sensitive C-reactive protein and orosomucoid levels were measured utilizing standard techniques. Oxysterol levels were measured by isotope-dilution gas chromatography/mass spectrometry. Standard lipid profile, serum glucose, high-sensitive C-reactive protein and orosomucoid levels were similar between the two studied populations. Compared to the control group, children with Autism Spectrum Disorders showed a significant higher plasma level of 24-hydroxycholesterol, while borderline significance was observed for 7α-hydroxycholesterol, and 25-hydroxycholersterol. In patients, 24-hydroxycholesterol was inversely correlated with age. Multivariate analysis showed that high plasma levels of 24-hydroxycholesterol are independent risk factors for Autism Spectrum Disorders. On the other hand, an analysis of the receiver's operating characteristics proved that the measured parameters recorded satisfactory levels of specificity and sensitivity. The present study provides evidence that Autism Spectrum Disorders are associated with altered levels in circulating oxysterols. The finding that 24-hydroxycholesterol is an independent risk factor for the disease and suggests the use of this oxysterol as a diagnostic tool in Autism Spectrum Disorders.

[TAFRO syndrome and monoclonal gammapathy: Uncommon association!]. / Syndrome de TAFRO et gammapathie monoclonale : association inhabituelle !

Castleman's disease is a lymphoproliferative disorder characterized by angiofollicular lymph node hyperplasia. Recently, a new variant of multicentric Castleman's disease has been identified in Japan called TAFRO syndrome. It is characterized by a constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction and organomegaly (TAFRO). It is usually associated with polyclonal hyperimmunoglobulinemia. Here, we report the first and unique case of TAFRO syndrome with monoclonal gammapathy.

Relationship between biomarkers of muscle damage and redox status in response to a weightlifting training session: effect of time-of-day.

The aims of the present study were to: (1) investigate the effect of a weightlifting training session and time-of-day (TOD) upon biological parameters (i.e., oral temperature, hematological, C-reactive protein (CRP), and oxidative stress) and (2) assess their possible link with muscle damage responses. Nine weightlifters (21 ± 0.5 years) performed, in a randomized order, three Olympic-Weightlifting sessions (i.e., at 08:00, 14:00, and 18:00). Blood samples were collected at rest, 3 min and 48 h after each training session. Between pre- and post-training session, ANOVA showed significant increases in oxidative stress markers at the three TODs (p < 0.01) and significant increases for creatine kinase (CK) and lactate dehydrogenase (LDH) only at 08:00 and 18:00 (p < 0.05). At rest, the results showed a significant diurnal variation for the majority of the selected parameters except for malondialdehyde (MDA), total bilirubin, and CRP with higher values observed at 18:00 (p < 0.05). After the training session, given the higher rate of increase during the morning session, these diurnal variations persisted for temperature and WBC (p < 0.01) and were suppressed for CK, LDH, uric acid (UA), catalase, and glutathione peroxidase. The main significant correlations (p < 0.001) were observed between: (1) CK and MDA (r = 0.6) and CK and UA (r = 0.66 and r = 0.82) during the morning and evening training sessions; (2) CK and CRP only during the morning session (r = 0.5); and (3) CRP and WBC during the three training sessions (r = 0.8). In conclusion, the present findings: (1) confirm that the muscle damage responses could be induced by a high level of oxidative stress and (2) suggest to avoid scheduling training sessions in the morning given the higher muscle damage, inflammatory, and oxidative responses at this TOD.

Male hypogonadism and metabolic syndrome.

The role of androgens in cardiovascular disease is still controversial in men. In this study, we investigated metabolic disorders in Tunisian hypogonadal men compared with healthy controls. Forty hypogonadal men and 80 control subjects were enrolled. Patients with a history of pre-existing panhypopituitarism, thyroid dysfunction or inflammatory disease were excluded. Glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein (hsCRP), lipid profile, insulin, testosterone and gonadotrophins were measured. Insulin resistance was assessed by homoeostasis model assessment of insulin resistance (Homa IR). Waist circumference, body mass index and blood pressure were significantly higher in patients compared with controls. Glycemia, HbA1c, fasting serum insulin and Homa IR were significantly increased among hypogonadal men. In univariate analysis, testosterone levels were inversely correlated with body mass index, waist circumference, blood pressure, glycaemia, HbA1C, insulin, Homa IR and hsCRP. In multivariate analysis including all significant variables, initial testosterone level was the only independent risk factor for developing dyslipidaemia. With logistic regression, male hypogonadism was an independent risk factor for MS (P < 0.001). We conclude that low testosterone level plays a central role in the development of metabolic syndrome. Further prospective data are required to establish the causative link.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and variations of homocysteine concentrations in patients with Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a chronic, relapsing, multi-systemic inflammatory disorder of unknown causes. This disease is mainly characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The aim of this study is to investigate the associations between C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the plasma homocysteine (Hcy), folate, and B12 levels in a relatively large cohort of Tunisian patients with BD. METHODS: The study included 142 patients with BD and 172 healthy controls. The C677T and A1298C polymorphisms were genotyped using PCR-RFLP. Serum Hcy level was determined using a fluorescence polarization immunoassay. Serum folate and vitamin B12 levels were measured by electrochemiluminescence immunoassay. RESULTS: Genotype and allele frequencies of the two studied MTHFR polymorphisms did not show any significant differences among BD patients compared to controls. Patient carriers of the 677TT variant and the 677T allele displayed significantly higher Hcy concentration. Moreover, no significant association was found between neither A1298C polymorphism nor the C allele and Hcy, folate, and B12 levels. In multivariate analyses, we reported that 677T allele, male gender, and creatinine level were independent risk factors for hyperhomocysteinemia (HHC). CONCLUSIONS: In the present study, we report the absence of any significant differences between genotype and allele frequencies for both studied polymorphisms among BD patients compared to healthy controls. Besides, we showed that the T allele of MTHFR C677T polymorphism influenced the Hcy level which is an independent risk factor for HHC in Tunisian BD patients.

[Increased cardiovascular risk and premature atherosclerosis in rheumatoid arthritis]. / Augmentation du risque cardiovasculaire et accélération de l'athérosclérose au cours de la polyarthrite rhumatoïde.

UNLABELLED: Patients with rheumatoid arthritis (RA) are at increased risk of mortality compared with the general population. Evidence suggests that this increased mortality can largely be attributed to increased cardiovascular (CV) death. In a prospective study, 34 patients with RA were compared with age- and sex-matched controls. RESULTS: We found a lower C-HDL, apolipoprotein A1 and B in patients with RA. However, CT/C-HDL and C-LDL/C-HDL were significantly higher than control patients. The intima-media thickness was significantly higher in patients with RA (0.759 mm vs 0.558 mm; P<0.001). CONCLUSION: Increased attention to cardiovascular risk in RA will be necessary to reduce the excess CV mortality and morbidity in RA patients. It appears that the excess risk that is observed in the RA population can be explained, in part, by promotion of CV disease through increased systemic inflammation associated with RA.

[Lipid profile in maintenance haemodialysis]. / Profil lipidique dans l'insuffisance rénale chronique au stade d'hémodialyse.

INTRODUCTION: The chronic kidney failure is a source of dyslipidemia and accelerated atherosclerosis. No changes in the lipoprotein profile could be reversed by dialysis. OBJECTIVE: Our aim was to study the lipid disturbances characteristics in end stage renal disease in order to assess their theorical atherogenic potential. SUBJECTS AND METHODS: The patient population consisted of 36 patients on maintenance haemodialysis. Matched control subjects were recruited among apparently healthy normolipidemic Tunisians. Total cholesterol, triglycerides, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, apolipoprotein AI and apolipoprotein B concentrations were measured. RESULTS: The triglycerides levels were significantly higher in patient group, unlike the high-density-lipoprotein cholesterol and apolipoprotein AI levels that were significantly reduced. We saw no increase in the levels of low-density-lipoprotein cholesterol and apolipoprotein B. The low-density-lipoprotein cholesterol/high-density-lipoprotein cholesterol ratio result wasn't helpful in the evaluation of the atherogenic risk. CONCLUSION: We confirm the quantitative lipid disorders associated with maintenance haemodialysis. The assessment of cardiovascular risk on the basis of these disorders seems difficult.