Gluten-free diet induces rapid changes in phenotype and survival properties of gluten-specific T cells in celiac disease.
Demonstrates that gluten-specific CD4+ T cells in blood rapidly change phenotype and decrease in number when celiac disease patients with active disease starts with a gluten-free diet. Along with the drop in IgA TG2 antibodies these changes can be used to monitor the effect of drugs in patients with untreated celiac disease who continue to be exposed to gluten.
Biopsy proteome scoring to determine mucosal remodeling in celiac disease.
Describes development of computational tools to transform mass-spectrometry based proteomics data into a numerical score that reflect gluten-induced mucosal inflammation. Such a tool will be of high value as novel effect measure for clinical drug trials.
Autoantibody binding and unique enzyme-substrate intermediate conformation of human transglutaminase 3.
Describes how autoantibody binding can favor/modulate enzyme catalysis that together provide mechanistic insight into selection and formation of autoantibodies towards enzymes.
Identification of gluten T cell epitopes driving celiac disease.
Proof-of-concept study that describes how flow-cytometry sorting of inflammatory T-cells based on phenotype can allow for identification of disease driving CD4+ T-cell epitopes.
The Immunobiology and Pathogenesis of Celiac Disease.
Updated review that provides a state-of-the art overview of coeliac disease pathogenesis.
Link to the publication in PubMed
The immuneML ecosystem for machine learning analysis of adaptive immune receptor repertoires.
Describes the development and validation of an integrated and automatic Machine Learning pipeline for benchmarking immune receptor analysis. Enables tailored and broad-scale analysis of NGS immune receptor libraries.
A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease.
Described the successful prevention of gluten-induced mucosal remodeling following oral administration of a small molecule drug that inhibits Transglutaminase 2 enzyme activity. Proof-of-concept of mechanism of treatment concept described by the Sollid group more than 25 years ago.
Longevity, clonal relationship, and transcriptional program of celiac disease-specific plasma cells.
Describes shared and unique characteristics of plasma cells specific either for exogenous antigen (deamidated gluten) or autoantigen (Transglutaminase 2) that help us understand their life cycle and and developmental trajectory as well as mechanism of formation.
A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease.
Describes the structural basis for how and why two highly homologous HLA-DQ2 molecules (HLA DQ2.2. and HAL DQ2.5) confer different disease risk. The difference results from differential ability to bind and present gluten peptides which ultimately shapes and drive different T cells responses.
B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2.
Hallmark paper that through the use of a transgenic mouse model expressing a celiac patient derived prototypic anti-Transglutaminase 2 specific B-cell receptor, demonstrates that B-cell tolerance to Transglutaminase 2 is regulated on the level of T-cell help. This paper also casts doubt about the true in vivo distribution and availability of TG2 as B-cell autoantigen, and as gluten-converting enzyme and drug target.
Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions.
By use of HLA-DQ2:gluten tetramers, mass cytometry RNA Seq analysis, the phenotype of gluten-specific CD4+ T cells is characterized. The deep phenotyping reveals a surprisingly narrow phenotype which indicate a function of the cells to provide T-cell help to B cells.