Clinical and multi-omics cross-phenotyping of patients with autoimmune and autoinflammatory diseases: the observational TRANSIMMUNOM protocol

Abstract

Introduction: Autoimmune and autoinflammatory diseases (AIDs) represent a socioeconomic burden as the second cause of chronic illness in Western countries. In this context, the TRANSIMMUNOM clinical protocol is designed to revisit the nosology of AIDs by combining basic, clinical and information sciences. Based on classical and systems biology analyses, it aims to uncover important phenotypes that cut across diagnostic groups so as to discover biomarkers and identify novel therapeutic targets.

Methods and analysis: TRANSIMMUNOM is an observational clinical protocol that aims to cross-phenotype a set of 19 AIDs, six related control diseases and healthy volunteers . We assembled a multidisciplinary cohort management team tasked with (1) selecting informative biological (routine and omics type) and clinical parameters to be captured, (2) standardising the sample collection and shipment circuit, (3) selecting omics technologies and benchmarking omics data providers, (4) designing and implementing a multidisease electronic case report form and an omics database and (5) implementing supervised and unsupervised data analyses.

Ethics and dissemination: The study was approved by the institutional review board of Pitié-Salpêtrière Hospital (ethics committee Ile-De-France 48-15) and done in accordance with the Declaration of Helsinki and good clinical practice. Written informed consent is obtained from all participants before enrolment in the study. TRANSIMMUNOM's project website provides information about the protocol (https://www.transimmunom.fr/en/) including experimental set-up and tool developments. Results will be disseminated during annual scientific committees appraising the project progresses and at national and international scientific conferences.

Discussion: Systems biology approaches are increasingly implemented in human pathophysiology research. The TRANSIMMUNOM study applies such approach to the pathophysiology of AIDs. We believe that this translational systems immunology approach has the potential to provide breakthrough discoveries for better understanding and treatment of AIDs.

Trial registration number: NCT02466217; Pre-results.

Keywords: autoimmunity; data integration; inflammation; multidisciplinarity.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

TRANSIMMUNOM overview of the study. The figure represents the implementation of the study summarised in three steps. Step 1: protocol definition, sample circuit, electronic case report form (e-CRF); Step 2: recruitment, sample collection, omics analysis and data implementation and Step 3: data cross-analysis. The three steps are shown chronologically following the timeline of the study.

Figure 2

TRANSIMMUNOM multidisciplinary cohort management team (CMT). The figure represents the staff involved in the CMT grouped by major discipline (biologists (purple), clinicians (blue), bioinformaticians/statisticians/computer scientists (green)) and their respective role in the implementation of the different aspect of the study (ellipse). Tasks are described following disciplinary colour code described above.

Figure 3

TRANSIMMUNOM participant chart. This chart describes the TRANSIMMUNOM group of participants with respect to the autoinflammatory disease (AID) continuum. The TRANSIMMUNOM group is composed of patients affected by either one of the 10 AID families displayed in the chart or a control disease or an unclassified AID, as well from healthy volunteers (HV). Colour gradient bars represent the contribution of autoimmunity (blue) and autoinflammation (red) across the continuum. Each AID family is positioned along these gradients according to current knowledge, together with its respective prevalence (in parentheses) per 100 000 individuals in European Union (*) or per 60 million individuals in France (**) and, when applicable, the associated control diseases (italic). Unclassified AIDs appear across the continuum as the autoimmune/autoinflammatory processes proportions remained to be determined. HV are part of the TRANSIMMUNOM participants. Altogether the group is composed of 19 AIDs, including familial mediterranean fever, ulcerative colitis, Crohn’s disease, spondyloarthritis, rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, polymyositis, dermatomyositis, inclusion-body myositis and antisynthetase-related myositis (grouped into myositis), Churg-Strauss disease and granulomatosis with polyangiitis (vasculitis antineutrophil cytoplasmic antibodies (ANCA) related) and Behçet’s disease, cryoglobulinaemia and Takayasu (vasculitis non-ANCA-related) (grouped into vasculitis family); six control diseases, including TRAPS/CAPS, osteoarthrosis, muscular dystrophy, type 2 diabetes and antiphospholipid antibody syndrome (APLS) (adapted from McGonagle and Mc Dermott2).