Parkinson’s disease (PD) etiology is heterogeneous, genetic, and multi-factorial, resulting in a varied disease from a mild slow progression to a more severe rapid progression. Prognostic information on the nature of the patient’s disease at diagnosis aids the physician in counseling patients on treatment options and life planning. In a cohort of PD patients from the PPMI study, the relative gene expression levels of SKP1A, UBE2K, ALDH1A1, PSMC4, HSPA8 and LAMB2 were measured in baseline blood samples by real-time quantitative PCR. At baseline PD patients were up to 2 years from diagnosis, H&Y scale ≤ 2 and PD treatment naïve. PD-Prediction algorithm comprised of ALDH1A1, LAMB2, UBE2K, SKP1A and age was created by logistic regression for predicting progression to ≤ 70% Modified Schwab and England Activities of Daily Living (S&E-ADL). In relation to patients negative for PD-Prediction (n = 180), patients positive (n = 30) for Cutoff-1 (at 82% specificity, 80.0% sensitivity) had positive hazard ratio (HR+) of 10.6 (95% CI, 2.2–50.1), and positive (n = 23) for Cutoff-2 (at 93% specificity, 47% sensitivity) had HR+ of 17.1 (95% CI, 3.2–89.9) to progress to ≤ 70% S&E-ADL within 3 years (P value < 0.0001). Likewise, patients positive for PD-Prediction Cutoff-1 (n = 49) had HR+ 4.3 (95% CI, 1.6–11.6) for faster time to H&Y 3 in relation to patients negative (n = 170) for PD-Prediction (P value = 0.0002). Our findings show an algorithm that seems to predict fast PD progression and may potentially be used as a tool to assist the physician in choosing an optimal treatment plan, improving the patient’s quality of life and overall health outcome.

Introduction: Our previous findings showed that the microRNA (miR) expression profile of miR-151, miR-1290 and miR-451 measured in bone marrow (BM) aspirations taken at diagnosis can predict risk of relapse in pediatric acute lymphoblastic leukemia (ALL) patients treated according to BFM and DCOG protocols (Avigad et al., Genes, Chromosomes & Cancer; 55:328-339, 2016). The development of a minimally invasive blood test for predicting relapse in pediatric B-ALL patients can greatly benefit patients. Therefore, the aim of this current retrospective exploratory study was to investigate the predictive ability of miR-151-5p, miR-1290 and miR-451 measured in peripheral blood lymphocytes (PBL) at diagnosis.

Background: Anti-glycan antibodies can be found in autoimmune diseases. IgM against glycan P63 was identified in clinically isolated syndromes (CIS) and included in gMS-Classifier2, an algorithm designed with the aim of identifying patients at risk of a second demyelinating attack.Objective: To determine the value of gMS-Classifier2 as an early and independent predictor of conversion to clinically definite multiple sclerosis (CDMS).Methods: Data were prospectively acquired from a CIS cohort. gMS-Classifier2 was determined in patients first seen between 1995 and 2007 with >= two 200 mu L serum aliquots (N = 249). The primary endpoint was time to conversion to CDMS at two years, the factor tested was gMS-Classifier2 status (positive/negative) or units; other exploratory time points were 5 years and total time of follow-up.Results: Seventy-five patients (30.1%) were gMS-Classifier2 positive. Conversion to CDMS occurred in 31/75 (41.3%) of positive and 45/174 (25.9%) of negative patients (p = 0.017) at two years. Median time to CDMS was 37.8 months (95% CI 10.4-65.3) for positive and 83.9 months (95% CI 57.5-110.5) for negative patients. gMS-Classifier2 status predicted conversion to CDMS within two years of follow-up (HR = 1.8, 95% CI 1.1-2.8; p = 0.014). gMS-Classifier2 units were also independent predictors when tested with either Barkhof criteria and OCB (HR = 1.2, CI 1.0-1.5, p = 0.020) or with T2 lesions and OCB (HR = 1.3, CI 1.1-1.5, p = 0.008). Similar results were obtained at 5 years of follow-up. Discrimination measures showed a significant change in the area under the curve (Delta AUC) when adding gMS-Classifier2 to a model with either Barkhof criteria (Delta AUC 0.0415, p = 0.012) or number of T2 lesions (Delta AUC 0.0467, p = 0.009), but not when OCB were added to these models.Conclusions: gMS-Classifier2 is an independent predictor of early conversion to CDMS and could be of clinical relevance, particularly in cases in which OCB are not available.

OBJECTIVE: To study the performance of gMSDx for diagnosis of multiple sclerosis (MS), in a prospective cohort of neurological patients, undergoing “real-life” diagnostics workup. BACKGROUND: Blood IgM anti -Glc(α-1,4)Glc(α) (anti -GAGA4) levels studied by a new test (gMSDx) seem to differentiate clinically isolated syndrome (CIS) / or relapsing remitting multiple sclerosis (RRMS) from other neurological diseases (OND). DESIGN/METHODS: 281 neurological patients were recruited and followed for at least 12 months. Clinical data and sera were collected at the beginning of the study. MS Diagnosis was defined by McDonald 2010 criteria. Frozen sera were analyzed for gMSDx (Glycominds, US). Patients were characterized using a previously defined cutoffs, as positive if >55, or high positive if >80 EU/(Total IgM mg/mL) 0.5. RESULTS: 136 patients (69% females) were diagnosed as MS, 9 remained as CIS or radiological isolated syndrome, 136 (55% females) were diagnosed as other neurological disease (OND). MS patients had significantly higher levels of IgM anti-GAGA4 normalized to total IgM than OND patients (p=0.004). 47/136 MS patients were positive vs. 26/136 OND (p= 0.009). Sensitivity, specificity, positive and negative likelihood ratios at cutoff>55EU/(Total IgM mg/mL) 0.5 were: 35%, 81%, 1.8 and 0.8; at cutoff>80EU/(Total IgM mg/mL) 0.5 were: 12.5%, 94%, 2.1 and 0.9. In the OND group, only 7/136 were high positive (95% specificity). CONCLUSIONS: This first prospective analysis of a “real life” consecutive cohort validates that gMSDx blood test discerns a subgroup of CIS/RRMS from OND. Supported by: Glycominds, Ltd. Disclosure: Dr. Villar has received personal compensation from Biogen Idec, Bayer Schering, and Merck Serono. Dr. Garcia-Caldentey has nothing to disclose. Dr. Costa-Frossard has received personal compensation for activities with Biogen Idec, Novartis, and Bayer Pharmaceuticals Corporation. Dr. Dotan has received personal compensation for activities with Glycominds Ltd. as an employee. Dr. Dotan holds stock and/or stock options in Glycominds Ltd., which sponsored research in which Dr. Dotan was involved as an investigator. Dr. Dukler has received personal compensation for activities with Glycominds as an employee. Dr. Dukler has received compensation for serving on the board of Glycominds. Dr. Dukler holds stock and/or stock options in Glycominds. Dr. Alvarez-Cermeno has nothing to disclose.

Objectives: We evaluated the presence of anti-glycan antibodies (aGA) in patients with antiphospholipid syndrome (APS), and associations between aGA and clinical features of the disease.Methods: Sera from APS patients and healthy controls were analyzed for aGA levels by ELISA. Analysis of the association of specific aGA with clinical manifestations of APS was performed. Selected aGA were affinity-purified and injected intravenously into naive mice which were tested for fetal loss. Matrigel invasion assay was performed for detection of choriocarcinoma cells (JAR) invasion and proliferation in the presence of selected aGA. Culture fluid of JAR invasion assays was analyzed for the presence of MMP2 and MMP9.Results: High levels of several aGA were found in APS sera, of which anti-GalNAc-beta was significantly associated with recurrent pregnancy loss. Naive mice infused intravenously with anti-GalNAc-beta developed increased fetal loss. Anti-GalNAc-beta significantly inhibited the in-vitro percentage of JAR invasiveness and the secretion of MMP2 and MMP9 by human JAR cells.Conclusions: APS sera contain significant levels of aGA directed against several glycans. Anti-GalNAc-beta Ab is specifically associated with recurrent pregnancy loss both in human patients and experimental mouse model. The pathogenic effects of anti-GalNAc-beta include inhibition of JAR cells invasiveness accompanied by decreased MMP2 and MMP9 secretion. (C) 2012 Elsevier Ltd. All rights reserved.

Introduction: Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon.Methods: 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course.Results: Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed.Conclusions: While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time.

BACKGROUND:We tested a panel of novel serological anti-glycan antibodies including the previously unpublished anti-laminarin IgA (Anti-L) and anti-chitin IgA (Anti-C) carbohydrate antibodies for the presence in Crohn's disease (CD) patients, diagnosis and differentiation of CD, association with complicated disease behavior, and marker stability over time. METHODS:The presence of Anti-L, Anti-C, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-mannobioside IgG (AMCA), and anti-Saccaromyces cervisiae IgG (gASCA) carbohydrate antibodies were tested in serum samples from 824 participants (363 CD, 130 ulcerative colitis [UC], 74 other gastrointestinal diseases, and 257 noninflammatory bowel/gastrointestinal disease controls) of the German IBD-network by enzyme-linked immunosorbent assay (ELISA; Glycominds, Lod, Israel) and for perinuclear antineutrophil cytoplasmic antibody (pANCA) by immunofluorescence. RESULTS:In all, 77.4% of the CD patients were positive for at least 1 of the anti-glycan antibodies. gASCA or the combination of gASCA/pANCA remained most accurate for the diagnosis of CD, but the combined use of the antibodies improved differentiation of CD from UC. Several single markers as well as an increasing antibody response were independently linked to a severe disease phenotype, as shown for the occurrence of complications, CD-related surgery, early disease onset, and ileal disease location. This was observed for both quantitative and qualitative antibody responses. The antibody status remained stable over time in most IBD patients. CONCLUSIONS:A panel of anti-glycan antibodies including the novel Anti-L and Anti-C may aid in differentiation of CD from UC, is associated with complicated CD behavior and IBD-related surgery, and is stable over time in a large patient cohort.

BACKGROUND:A high proportion of patients with Crohn's disease (CD) over time develop complications like fistulae and strictures, requiring surgery. We tested a panel of antiglycan antibodies for predicting the occurrence of complications and CD-related surgery in an adult patient cohort.METHODS:Serum samples of 149 CD patients of the German inflammatory bowel disease (IBD) network were tested for the presence of anti-laminarin IgA (Anti-L), anti-chitin IgA (Anti-C), anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-mannobioside IgG (AMCA), and anti-Saccaromyces cerevisiae IgG (gASCA) carbohydrate antibodies by enzyme-linked immunosorbent assay (ELISA) (IBDX(R) panel, Glycominds, Lod, Israel) in a blinded fashion. Clinical data were available on occurrence of complicated disease or CD-related surgery as well as disease activity, onset, and location.RESULTS:The median follow-up of the patients without any previous complication or surgery at time of sample procurement was 53.7 months. Overall, 26.3% developed a complication and 17.1% underwent CD-related surgery, respectively. Positivity for gASCA, AMCA, ACCA, and Anti-L alone or an increasing frequency of positive serum antibodies independently predicted a faster progression toward a more severe disease course. Once a complication or surgery had occurred only positivity for Anti-L or more than 3 markers out of the whole panel indicated progression to an additional surgery or complication. The antibody status of most patients remained stable over time.CONCLUSIONS:This is the first study showing the clinical value of serum antiglycan antibodies for prediction of a more complicated disease course in adult patients with CD.