Natalizumab modulates the humoral response against HERV-Wenv73-88 in a follow-up study of Multiple Sclerosis patients

Multiple Sclerosis (MS) is a heterogeneous disorder of the central nervous system (CNS) that begins as an inflammatory autoimmune disorder mediated by auto-reactive lymphocyte followed by microglial activation and chronic degeneration. The etiology of Multiple Sclerosis (MS) is unknown but several data support the hypothesis of possible infectious agents which may act as a trigger for the pathogenic cascade. Human endogenous retrovirus (HERV-W/MSRV), Epstein Barr Virus (EBV) and Mycobacterium avium ss. paratuberculosis (MAP) have been associated to Multiple Sclerosis. In this study, we evaluated the humoral response against different peptides: the human endogenous retrovirus HERV-Wenv73-88, MAP106c121-132 from MAP, EBNA1 400-413 from EBV and the homologous human peptide MBP85-98 in a cohort of MS patients treated with natalizumab. Results showed a statistically significant difference in the response against the HERV-W peptide in MS patients after two years of natalizumab treatment

REAC regenerative treatment efficacy in experimental chondral lesions: a pilot study on ovine animal model

Eraldo Sanna Passino,1,2 Stefano Rocca,1 Sabrina Caggiu,1 Nicolò Columbano,1,2 Alessandro Castagna,3 Vania Fontani,3–5 Salvatore Rinaldi3–51Department of Veterinary Medicine, University of Sassari, Sassari, Italy; 2Comparative Surgery Research Laboratory, University of Sassari, Sassari, Italy; 3Department of Regenerative Medicine, Rinaldi Fontani Institute, Florence, Italy; 4Research Department, Rinaldi Fontani Foundation, Florence, Italy; 5Research Department, IRF Shanghai Biomedical Sciences, Shanghai, People’s Republic of China Abstract: Radioelectric asymmetric conveyor (REAC) technology is a platform designed to optimize cell polarity. Cell polarity is a universal biological phenomenon that is implicated in cell differentiation, proliferation, morphogenesis, aging, and rejuvenation. In this work, we investigate a timing and administration protocol for tissue optimization regenerative treatment type C, in order to treat aging-related chondral damage or injuries and gain insights into regenerative processes of articular cartilage in humans. The chondral lesion produced in this study in an animal model (6 knee joints of 4 adult sheep) was 6 mm in diameter and about 2 mm deep. These lesions, which did not involve subchondral bone, tend to increase in size and depth and are not completely repaired with normal hyaline articular cartilage since adult articular cartilage is avascular and has a very slow turnover at the cellular and molecular level. Moreover, the hydration of articular cartilage is reduced with aging and with decreased mitotic activity, synthesis, and population size of chondrocytes. Six months posttreatment, lesions appeared filled, though not completely, with newly generated tissue of the light opalescent color of healthy articular cartilage, which otherwise covered the underlying subchondral bone. The newly formed tissue surface appeared to be quite regular. Nearly complete regeneration of subchondral bone occurred, with little vascularization and ossification nuclei almost absent. The results of this study confirm previous data obtained in vitro on the regenerative effects of REAC technology on human normal and osteoarthritic chondrocytes exposed to IL-1β. The present findings indicate that REAC tissue optimization-regenerative treatment type C is a promising therapeutic tool among the other REAC regenerative treatment protocols for the treatment of cartilage lesions. Keywords: aging, senescence, articular cartilage, regenerative medicine, regenerative physical treatments, radio electric asymmetric conveye

Risk factors of gastrointestinal parasites lungworms ticks and lice in donkeys in the Asinara national park (Sardinia, Italy)

From June to November 2015 a total of 113 Asinara donkeys (41 albino, 72 coloured) were sampled (91 fecal samples from 36 albino and 55 grey donkeys). All donkeys were surveyed for ticks and lice. Sedimentation, Baermann and modified McMaster methods were performed for endoparasites. The EPG/OPG were calculated. Larval cultures were performed and L3 were recovered by a Baermann technique. Ectoparasites were morp olo lly nt f T nf t on\u2018s t ks l v l w r r or f n n 3 t or s: no infestation, low (1-10 ticks) and high infestation (>10 ticks). Three land cover types were defined to estimate the risk: sparse vegetation; mediterranean shrubland; grassland. Statistical analysis were performed through GLM with a ordinal logistic regression (SPSS 20.0, Chicago, IL). Ninety out of ninety-one donkeys were infected by intestinal strongyles (98.9%), Strongyloides (6.6%), Parascaris equorum (15.4%), Oxyuris equi (2.2%) and Eimeria leukarti (2.2%). No eggs of cestodes and trematodes were found. Dictyocaulus arnfieldi L1 were found in 46.1% of samples. Fecal pools were positive for Cyathostominae (61%), large strongyles (30%) and Trichostrongylus axei (9%) L3. Strongyles showed the highest egg excretion (mean abundance=1176.4 EPG; min-max=0-4575 EPG). Significant risk factors associated to strongyle infection (EPG) were: season;geographical distribution of herds and the land cover types. Egg shedding was 10.887 times higher in autumn than in summer and 2.865 times higher in donkeys from the North than those in the rest of the island. Donkeys from spare vegetation areas shed more eggs than other animals (OR=2.507). Albino and young donkeys were more at risk for P. equorum than coloured and old donkeys (OR=4.289 and OR=0.978 respectively). D. arnfieldi larvae shedding was higher in autumn than in summer (OR=5.577). Haemaphysalis punctata (46.2%), Hyalomma marginatum (10.7%) and Rhipicephalus bursa (43.1%) were found. A total of 58.4% (66/113) of donkeys were infested by ticks (28.3% albino; 30.1% coloured). The prevalence was 78% (32/41) and 47% (34/72) respectively in albino and coloured donkeys. Albino donkeys group had the highest percentage with high infestation (39% vs 15%; OR=2.865; P=0.021). The highest p r nt of onk ys w t no t ks 57 77% w r from l n w t \u2015sp rs v t t on\u2016 and had a low number of ticks (OR=0.185; P=0,001) than donkeys from other areas. Haematopinus asini were found on nine donkeys (8%), 8 albino and 1 coloured (OR=17.212, 95% CI 2.067-143,321, P= 0.009). Significant risks to tick infestation were associated to the colour of coat and the types of land cover. Albino donkeys show a 3.120 times higher risk than coloured donkeys to be infected by ticks. Donkeys from areas with sparse vegetation cover showed a lower risk to be infected by ticks (OR=0.227). 1. Garippa G, Sanna E, 1990. Ixodidi di frequente riscontro nei mammiferi dell'Asinara. Parassitol 32 (suppl. 1), 7-8 2. Pinna W, Vacca GM, Cubeddu G, Pintori G, Garippa G, 1994. Salvaguardia degli asinelli bianchi dell'Asinara: ri sultati di unintervento di controllo delle parassitosi. Ric. Biol. Selv. 24: 105-11

Identification of a HERV-K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross-sectional case–control study

Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19–37, env-su109–126, env-su164–186, env-su209–226) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann–Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19–37) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19–37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases

BACKGROUND AND PURPOSE: Human endogenous retroviruses-K/W seem play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) of ALS, multiple sclerosis (MS) and Alzheimer's disease (AD) patients, and in healthy controls (HCs). METHODS: Four antigenic peptides derived respectively from HERV-K and HERV-W env surface proteins were studied in twenty-one definite or probable ALS, twenty-six possible or definite relapsing-remitting (RR) MS, eighteen patients with AD and thirty-nine HCs. An indirect ELISA was set up to detect specific antibodies (Abs) against env surface peptides. RESULTS: Among the measured levels of Abs against the four different HERV-K peptide fragments, HERV-K env-su 19-37 only was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, among the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su 93-108 and HERV-W env-su 248-262 were significantly elevated, in serum and CSF of MS, compared to other groups. In ALS patients, the HERV-K env-su 19-37 antibodies levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. CONCLUSIONS: Increased circulating levels of Abs directed against the HERV-W env-su 93-108 and HERV-W env-su 248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su19-37 peptide fragment could serve as possible early novel biomarker in patients with ALS. This article is protected by copyright. All rights reserved