scholarly journals A personalized network framework reveals predictive axis of anti-TNF response across diseases

2021 ◽  
Author(s):  
Shiran Gerassy-Vainberg ◽  
Elina Starosvetsky ◽  
Renaud Gaujoux ◽  
Alexandra Blatt ◽  
Naama Maimon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Response ◽  
Computational Approach ◽  
High Dimensional ◽  
Biomarker Identification ◽  
Individual Level ◽  
Medical Need ◽  
Inflammatory Bowel ◽  
Intermediate Monocytes ◽  
Blood Data

Personalized treatment of complex diseases is an unmet medical need pushing towards drug biomarker identification of one drug-disease combination at a time. Here, we used a novel computational approach for modeling cell-centered individual-level network dynamics from high-dimensional blood data to predict infliximab response and uncover individual variation of non-response. We identified and validated that the RAC1-PAK1 axis is predictive of infliximab response in inflammatory bowel disease. Intermediate monocytes, which closely correlated with inflammation state, play a key role in the RAC1-PAK1 responses, supporting their modulation as a therapeutic target. This axis also predicts response in Rheumatoid arthritis, validated in three public cohorts. Our findings support pan-disease drug response diagnostics from blood, implicating common mechanisms of drug response or failure across diseases.

Fr546 INTERVENTIONS TO INCREASE VACCINATIONS RATES WITH INFLAMMATORY BOWEL DISEASE AND RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 160 (6) ◽  
pp. S-357
Author(s):  
Jalpa Patel ◽  
Dina Fakhouri ◽  
Mohamed Noureldin ◽  
Iris Kovar-Gough ◽  
Francis A. Farraye ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Meta Analysis ◽  
Inflammatory Bowel

scholarly journals Solar Radiation and Vitamin D: Mitigating Environmental Factors in Autoimmune Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Gerry K. Schwalfenberg
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Autoimmune Disease ◽  
Solar Radiation ◽  
Inflammatory Bowel

This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune disease are discussed. An example of the utility of supplementing vitamin D in an unusual autoimmune disease, idiopathic thrombocytic purpura, is presented.

scholarly journals SAT0006 SIMULTANEOUS ANALYSIS OF ANTI-CCP, RHEUMATOID FACTOR, ANTI-PAD4 AND ANTI-CARBAMYLATED PROTEIN ANTIBODIES REVEALS INTERACTION EFFECTS WITH RESPONSE TO ANTI-TNF THERAPY IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 933.2-934
Author(s):  
A. Julià ◽  
M. Lopez Lasanta ◽  
F. Blanco ◽  
A. Gómez ◽  
I. Haro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
Clinical Response ◽  
Therapeutic Approach ◽  
Drug Response ◽  
Single Marker Analysis ◽  
Das28 Score ◽  
Positive Interaction ◽  
Single Marker ◽  
Necrosis Factor

Background:Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 2 out of 3 Rheumatoid Arthritis patients. Identifying the patients that will not respond to this therapeutic approach is a major translational goal in RA. Association of seropositivity to rheumatoid factor (RF) or anti-cyclic-citrullinated antibodies (anti-CCP) with anti-TNF response has proven inconclusive, suggesting that other yet unexplored biomarkers could be more informative for this goal.Objectives:We tested the association of two recently introduced biomarkers in RA: anti-carbamylated protein antibodies (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4).Methods:A prospective cohort of n=80 RA patients starting anti-TNF therapy was recruited and levels for all four autoantibodies -RF, anti-CCP, anti-CarP and anti-PAD4- were measured at baseline. The change in DAS28 score between baseline and week 12 of therapy was used as the clinical endpoint.Results:Single marker-analysis showed no significant association with drug response. However, when testing for interactions between autoantibodies, we found highly significant associations with drug response. Anti-CCP and RF showed a positive interaction with the response to anti-TNF therapy (P=0.00068), and anti-PAD4 and antiCarP titers showed a negative interaction with the clinical response at week 12 (P=0.0062). Using an independent retrospective sample (n=199 patients), we validated the interaction between anti-CCP and RF with the clinical response to anti-TNF agents. (P=0.044).Conclusion:The results of this study show that interactions between antibodies are important in the response to anti-TNF therapy and suggest potential pathogenic relationships.Acknowledgments :We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaborationDisclosure of Interests:Antonio Julià: None declared, Maria Lopez Lasanta: None declared, Francisco Blanco: None declared, Antonio Gómez: None declared, Isabel Haro: None declared, Antonio Juan Mas: None declared, Alba Erra: None declared, Mª Luz García Vivar: None declared, Jordi Monfort: None declared, Simon Sánchez Fernandez: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Mercedes Alperi-López: None declared, Raúl Castellanos: None declared, Antonio Fernandez-Nebro: None declared, Cesar Diaz Torne: None declared, Núria Palau: None declared, Raquel M Lastra: None declared, Jordi Lladós: None declared, Raimon Sanmarti: None declared, Sara Marsal: None declared

scholarly journals FOXP3+T Regulatory Cell Modifications in Inflammatory Bowel Disease Patients Treated with Anti-TNFαAgents

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Luisa Guidi ◽  
Carla Felice ◽  
Annabella Procoli ◽  
Giuseppina Bonanno ◽  
Enrica Martinelli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Flow Cytometry ◽  
Bowel Disease ◽  
Peripheral Blood ◽  
Disease Duration ◽  
Healthy Controls ◽  
T Regulatory Cell ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factorα(TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+(Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFαtherapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3+cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFαtherapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD). No significant differences were found in LP FOXP3+cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFαmay affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.

scholarly journals Infer disease-associated microbial biomarkers based on metagenomic and metatranscriptomic data

2021 ◽  
Author(s):  
Zhaoqian Liu ◽  
Qi Wang ◽  
Dongjun Chung ◽  
Qin Ma ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Low Rank ◽  
Connected Components ◽  
Biomarker Identification ◽  
Gene Expression Matrix ◽  
Large Size ◽  
Microbial Biomarkers ◽  
Key Species ◽  
Novel Method ◽  
Inflammatory Bowel ◽  
Disease Subtypes

AbstractUnveiling disease-associated microbial biomarkers (e.g., key species, genes, and pathways) is an efficient strategy for the diagnosis and therapy of diseases. However, the heterogeneity and large size of microbial data bring tremendous challenges for fundamental characteristics discovery. We present IDAM, a novel method for disease-associated biomarker identification from metagenomic and metatranscriptomic data, without requiring prior metadata. It integrates gene context conservation and regulatory mechanism through a mathematical model for maximizing the number of connected components between local-low rank submatrices of a gene expression matrix and known uber-operon structures. We applied IDAM to 813 inflammatory bowel disease-associated datasets and showed IDAM outperformed existing methods in microbial biomarker identification. In addition, the identified biomarkers successfully distinguished disease subtypes and showcased their power in discovering novel disease subtypes/states. IDAM is freely available at https://github.com/OSU-BMBL/IDAM.

Pre-rheumatoid arthritis

2020 ◽  
pp. 121-132
Author(s):  
Karim Raza ◽  
Catherine McGrath ◽  
Laurette van Boheemen ◽  
Dirkjan van Schaardenburg
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
At Risk ◽  
Genetic Risk ◽  
Inflammatory Arthritis ◽  
Primary Site ◽  
Individual Level ◽  
Mucosal Surfaces ◽  
Risk Patients ◽  
The Individual

The typical evolution of rheumatoid arthritis (RA) is that a person, with genetic risk factors, develops autoantibodies and subclinical inflammation under relevant environmental influences. There are indications that the primary site of the pathology is at mucosal surfaces (e.g. in the gums, lungs, and/or the gut), after which the disease translocates to the joints. Preclinical RA can be defined at the phase during which no clinically apparent features are present (i.e. no symptoms of inflammatory arthritis or clinically apparent joint swelling) but during which RA related biologic derangements such as the presence of autoantibodies are present. This chapter presents an overview of the risk factors, stages, and events occurring during the pre-RA phase. A better understanding of the factors involved will enable more accurate prediction of RA at the individual level and selection of high-risk individuals for inclusion in preventive studies. Several pharmacologic and non-pharmacologic studies aiming to prevent or delay the onset of RA in at-risk individuals are currently underway. It is hoped that such interventions in the pre-RA and indeed in the preclinical-RA phases will allow us to reduce the risk of RA and prevent RA developing in at least a proportion of at-risk patients.

scholarly journals P664 SB5 and reference adalimumab show cross-immunogenicity in patients with inflammatory bowel disease or rheumatoid arthritis

2019 ◽  
Vol 13 (Supplement_1) ◽  
pp. S451-S452
Author(s):  
J Gonçalves ◽  
G Myung ◽  
E Hong ◽  
M Park ◽  
D Jeong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals Epigenetics of Inflammatory Bowel Disease: Unraveling Pathogenic Events

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Beatriz Mateos ◽  
Cora Palanca-Ballester ◽  
Esteban Saez-Gonzalez ◽  
Inés Moret ◽  
Adrian Lopez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Inflammatory Bowel Diseases ◽  
Drug Response ◽  
Current Knowledge ◽  
Epigenetic Biomarkers ◽  
Bowel Diseases ◽  
Potential Applicability ◽  
Inflammatory Bowel ◽  
New Biomarkers

Abstract Epigenetics has emerged as a new and promising field in recent years. Because there exists a need to find new biomarkers and improve diagnosis, prognosis, and drug response for inflammatory bowel diseases, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to the clinical practice. In this review, we present an overview of the current knowledge and its potential applicability of this emerging field in inflammatory bowel diseases.

Sign in / Sign up

Export Citation Format

Share Document