Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Neutralizing antibodies (NAbs) against Interferon beta (IFNβ) are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS) patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNβ treatment.</p> <p>Methods</p> <p>We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNβ during the treatment period. Patients were classified as: group A, developing ≥ 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNβ formulations for at least one year. NAbs positivity was defined as NAbs titre ≥ 20 TRU.</p> <p>Results</p> <p>Seventeen patients (12.1%) were NAbs positive. NAbs positivity correlated with poorer clinical response (<it>p </it>< 0.04). As expected, the prevalence of NAbs was significantly lower in Group C (2.1%) than in Group A (17.0%) and Group B (17.0%). However, in the groups of patients with a poor clinical response (A, B), NAbs positivity was found only in a small proportion of patients.</p> <p>Conclusion</p> <p>The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNβ.</p

Isoprostanes in clinically isolated syndrome and early multiple sclerosis as biomarkers of tissue damage and predictors of clinical course

Background. Among several pathogenic mechanisms of axonal damage in Multiple Sclerosis (MS), oxidative stress (OS) plays a substantial role. Oxygen free radicals lead to lipid peroxidation and subsequent formation of Isoprostanes (IsoP), which can be quantified in the cerebrospinal fluids (CSF) as a reliable index of intrathecal OS. F2-IsoP were shown to be higher in MS patients as compared to controls, and they were proposed as index of neural damage. Although axonal damage is present in patients soon after the first clinical episode suggestive of MS, so far no study evaluated IsoP levels in patients at this stage. Objective: a) to compare F2-IsoP in CSF of MS patients at the disease-onset with those of healthy controls; b) to correlate F2-IsoP levels with Magnetic Resonance Imaging (MRI) measures of brain damage, such as T2-lesions, Gadolinium-enhancing lesions, spectroscopic values and brain atrophy; c) to assess the F2-IsoP role in detecting patients at higher risk of developing relapses. Methods: Thirty-nine patients with a first clinical attack suggestive of MS underwent neurological examination, lumbar puncture and conventional/spectroscopic MRI. Patients were followed-up for 2 years. Results. CSF F2-IsoP levels were higher in patients than in 22 controls (mean[SD] 123.4[185.8] vs 4.5[2.9]pg/ml; p<0.0001). IsoP were inversely related to normalised brain volume (NBV) (p=0.04) and to NAA/Cho (p=0.01). Over 2 years, clinical relapses occurred more frequently in patients with higher baseline IsoP levels than in those with lower IsoP (61% vs 27%; p=0.04). Conclusions. CSF F2-IsoP might be a potential biomarker of tissue damage in MS

Pronounced focal and diffuse brain damage predicts short-term disease evolution in patients with clinically isolated syndrome suggestive of multiple sclerosis

BACKGROUND: In clinically isolated syndrome (CIS), the role of quantitative magnetic resonance imaging (MRI) in detecting prognostic markers is still debated. OBJECTIVE: To evaluate measures of diffuse brain damage (such as brain atrophy and the ratio of N-acetylaspartate to creatine (NAA/Cr)) in patients with CIS, in addition to focal lesions, as predictors of 1-year disease evolution. METHODS: 49 patients with CIS underwent MRI scans to quantify T2-lesions (T2-L) and gadolinium-enhanced lesion (GEL) number at baseline and after 1 year. Along with 25 healthy volunteers, they also underwent combined MRI/magnetic resonance spectroscopy examination to measure normalized brain volumes (NBVs) and NAA/Cr. Occurrence of relapses and new T2-L was recorded over 1 year to assess disease evolution. RESULTS: Occurrence of relapses and/or new T2-L over 1 year divided patients with CIS into 'active' and 'stable' groups. Active patients had lower baseline NAA/Cr and NBV. Baseline T2-L number, GEL, NAA/Cr and NBV predicted subsequent disease activity. Multivariable logistic regression models showed that both 'focal damage' (based on T2-L number and GEL) and 'diffuse damage' (based on NBV and NAA/Cr) models predicted disease activity at 1 year with great sensitivity, specificity and accuracy. This was best when the four MRI measures were combined (80% sensitivity, 89% specificity, 83% accuracy). CONCLUSIONS: Quantitative MRI measures of diffuse tissue damage such as brain atrophy and NAA/Cr, in addition to measures of focal demyelinating lesions, may predict short-term disease evolution in patients with CIS, particularly when used in combination. If confirmed in larger studies, these findings may have important clinical and therapeutic implications

I tumori della mammella. Linee guida sulla diagnosi il trattamento e la riabilitazione

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal