Contactin-2 was recently identified as an autoantigen targeted by T-cells and

Contactin-2 was recently identified as an autoantigen targeted by T-cells and autoantibodies in multiple sclerosis (MS). 555 F(ab)2 fragment of goat anti rabbit IgG (H+L), “type”:”entrez-nucleotide”,”attrs”:”text”:”A21430″,”term_id”:”583533″,”term_text”:”A21430″A21430, Molecular Probes, Eugene, OR, USA) during 1 h at room temperature. Results were photographed under a fluorescence microscope using Zeiss Axiovision software (Zeiss, Thornwood, NY). The results were evaluated by 3 investigators (AB, LS, AS) blinded to the clinical data. Contactin-2-ab-positive samples were evaluated with a similar cell-based assay for the presence of antibodies against proteins associated with contactin-2: leucine-rich glioma inactivated 1 (LGI1) and contactin associated protein-like 2 (Caspr2) (Lai et al., 2010). 2.3. MG-132 Statistical analysis Chi-squared or Fisher exact test were performed to compare categorical variables. Comparisons between continuous variables were performed using t-test. KaplanCMeier analysis was used to estimate cumulative survival probabilities for time to reach an EDSS (Expanded Disability Status Scale) MG-132 endpoint of 3.0, 4.0 and 6.0. All significant results were set at two-tailed p-value < 0.05. All statistical analysis was performed by software SPSS version 18.0. 3. Results The demographics and clinical RFC37 characteristics of the patients included in the study are shown in Table 1. Contactin-2-ab were found in the serum of 4 of the 51 (7.8%) relapsingCremitting patients (Fig. 1). The rest of the samples analyzed, including the available CSF of 3 of the positive patients and the control samples, were negative. Positive samples didn’t present antibodies against Caspr2 or LGI1. The scientific and MRI features from the positive sufferers were heterogeneous however, not significantly not the same as the others of relapsingCremitting sufferers with regards to demographics, relapses, impairment and many years of follow-up (Desk 2). There have been also MG-132 no significant distinctions in the analyzed MRI features (offered by enough time of sampling in 37 harmful sufferers as well as the 4 positive sufferers) (Desk 2). A fresh serum sample from the 4 positive sufferers was examined after a median follow-up of 9 years (8C14 years), as well as the antibodies continued to be positive in every of them. Through the follow-up, 1 (25%) from the positive sufferers and 11 (23.4%) from the bad sufferers developed the extra progressive type of the condition (Desk 2). Fig. 1 Recognition of antibodies to contactin-2 utilizing a cell-based assay. Binding of antibodies from an optimistic patient to the top of HEK293 cells transfected with individual contactin-2 cDNA clone (A; green); the cells had been coincubated using a rabbit antibody against … Desk 1 Demographic and clinical characteristics from the patients contained in the scholarly research. Desk 2 Demographic, scientific and MRI characteristics of relapsingCremitting patients. 4. Discussion This study confirms the presence of an autoantibody response to surface epitopes of contactin-2 in a minority of MS patients. The presence of contactin-2-ab was not consistently associated with a particular clinical profile at the time of detection or with a different evolution at long term. Autoantibody response to contactin-2 was first identified in MS by proteomic approach (Derfuss et al., 2009). Contactin-2-ab were detected by ELISA not only in MS patients but also in patients with other neurological diseases, and healthy controls. However, when antibodies against surface epitopes of contactin-2 were tested on cell lines transfected with contactin-2 by flow cytometry, only 2 of the 25 MS samples were positive (Derfuss et al., 2009), a similar frequency to that found in the current study. Contactin-2, a cell-adhesion molecule of the immunoglobulin superfamily, exists both as a glycophosphatidylinositol-linked cell surface isoform and as a released form. At the juxtaparanodal region of myelinated axons it is expressed around the glial membrane and on the axon as a contactin-2/Caspr2 heterodimer (Poliak et al., 2003; Savvaki et al., 2008; Derfuss et al., 2010). In this localization, the intact myelin sheath probably prevents antibodies to gain access to contactin-2 in the juxtaparanodal region. In fact, MG-132 contactin-2-ab failed to cause any additional damage when injected to experimental animals with EAE induced by transfer of contactin-2-specific T-cells (Derfuss et al., 2009, 2010). Comparable results have been observed with antibodies to neurofascin, another recently identified autoantigen in MS (Mathey et al., 2007). Antibodies to surface epitopes of contactin-2 were recently detected in 5 of the 96 patients who had antibodies previously attributed to voltage-gated potassium channel (VGKC) (Irani et al., 2010). Four of the 5 positive samples also had additional antibodies..

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