Immune Tolerance Network

This common statement of the American Academy of Allergy, Asthma and Immunology (AAAAI) and The European Academy of Allergy and Clinical Immunology (EAACI) provides an update of the 2012 published guidelines on food challenges. The guidelines equally address food challenges in the research and the clinical settings. They first address the diagnostic tests which can guide the decision to conduct a challenge. Safety of food challenges is prime, and the various procedures and safety issues as well as medications potentially involved in challenges are extensively discussed. Challenges are suggested to be conducted with semi-logarithmic incremental doses based on the protein content, typically for IgE-mediated food allergy with intervals of 20-30 min between doses. Specific protocols for other types of reactions such atopic dermatitis or gastrointestinal food allergy are detailed separately. Proper stopping criteria are essential in order to reduce the risk of false-positive diagnoses, but also severe reactions. The guidelines recommend criteria based on "go on," "stop," or "observation." These revised guidelines will clearly provide much needed guidance for food challenges in the research and clinical settings. They will continue to evolve with new diagnostic tests or new needs in the field of food allergy.

Human type 1 diabetes (T1D) is caused by autoimmune attack on the insulin-producing pancreatic beta cells by islet antigen-reactive T cells. How human islet antigen-reactive (IAR) CD4+ memory T cells from peripheral blood affect T1D progression in the pancreas is poorly understood. Here, we aim to determine if IAR T cells in blood could be detected in pancreas. We identify paired αβ (TRA/TRB) T cell receptors (TCRs) in IAR T cells from the blood of healthy, at-risk, new-onset, and established T1D donors, and measured sequence overlap with TCRs in pancreata from healthy, at risk and T1D organ donors. We report extensive TRA junction sharing between IAR T cells and pancreas-infiltrating T cells (PIT), with perfect-match or single-mismatch TRA junction amino acid sequences comprising ~29% total unique IAR TRA junctions (942/3,264). PIT-matched TRA junctions were largely public and enriched for TRAV41 usage, showing significant nucleotide sequence convergence, increased use of germline-encoded versus non-templated residues in epitope engagement, and a potential for cross-reactivity. Our findings thus link T cells with distinctive germline-like TRA chains in the peripheral blood with T cells in the pancreas.

ObjectivesWe investigated whether soluble immune checkpoints (sICPs) predict treatment resistance, relapse and infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).MethodsPlasma sICP concentrations from available samples obtained during conduct of the RAVE trial were measured by immunoabsorbent assays from patients with either proteinase 3 (PR3) or myeloperoxidase (MPO)-ANCA vasculitis and were correlated with clinical outcomes, a set of biomarkers and available flow cytometry analyses focusing on T cell subsets. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J.ResultsAnalysis of 189 plasma samples at baseline revealed higher concentrations of sTim-3, sCD27, sLag-3, sPD-1 and sPD-L2 in patients with MPO-ANCA vasculitis (n=62) as compared with PR3-ANCA vasculitis (n=127). Among patients receiving rituximab induction therapy (n=95), the combination of lower soluble (s)Lag-3 (<90 pg/mL) and higher sCD27 (>3000 pg/mL) predicted therapy failure. Twenty-four out of 73 patients (32.9%) in the rituximab arm reaching remission at 6 months relapsed during follow-up. In this subgroup, high baseline values of sTim-3 (>1200 pg/mL), sCD27 (>1250 pg/mL) and sBTLA (>1000 pg/mL) were associated with both sustained remission and infectious complications. These findings could not be replicated in 94 patients randomised to receive cyclophosphamide/azathioprine.ConclusionsPatients with AAV treated with rituximab achieved remission less frequently when concentrations of sLag-3 were low and concentrations of sCD27 were high. Higher concentrations of sTim-3, sCD27 and sBTLA at baseline predicted relapse in patients treated with rituximab. These results require confirmation but may contribute to a personalised treatment approach of AAV.

Povzetek. V članku raziskujemo odnos večinskega prebivalstva tretjega največjega slovenskega mesta Celje do albanske priseljenske skupnosti, ki se je v zadnjem obdobju številčno okrepila in med večinskim prebivalstvom generira odklonilni odnos in etnično distanco. Na podlagi teoretskih predpostavk v polju sociologije in migracijskih študij je bil oblikovan raziskovalni načrt z integracijo metod. Analiza rezultatov je pokazala, da ima večinsko prebivalstvo prevladujoče negativen odnos, opazili smo delna ujemanja s predpostavljenimi teoretičnimi izhodišči, pri čemer se je pokazalo, da imajo posameznice z višjo izobrazbo in višjimi dohodki nekoliko bolj naklonjen odnos do priseljencev kot moški respondenti z nižjo izobrazbo in nižjimi prihodki. Ključni pojmi: priseljenci albanske narodnosti, odnos večinskega prebivalstva, albanofobija, Mestna občina Celje

The goal of personalized medicine is to match the right drugs to the right patients at the right time. Personalized medicine has been most successful in cases where there is a clear genetic linkage between a disease and a therapy. This is not the case with type 1 diabetes (T1D), a genetically complex immune-mediated disease of β-cell destruction. Researchers over decades have traced the natural history of disease sufficiently to use autoantibodies as predictive biomarkers for disease risk and to conduct successful clinical trials of disease-modifying therapy. Recent studies, however, have highlighted heterogeneity associated with progression, with nonuniform rate of insulin loss and distinct features of the peri-diagnostic period. Likewise, there is heterogeneity in immune profiles and outcomes in response to therapy. Unexpectedly, from these studies demonstrating perplexing complexity in progression and response to therapy, new biomarker-based principles are emerging for how to achieve personalized therapies for T1D. These include therapy timed to periods of disease activity, use of patient stratification biomarkers to align therapeutic target with disease endotype, pharmacodynamic biomarkers to achieve personalized dosing and appropriate combination therapies, and efficacy biomarkers for “treat-to-target” strategies. These principles provide a template for application of personalized medicine to complex diseases.

Oral Tolerance Induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.(1, 2) OTI to peanut is highly effective in a high-risk population with an 81% relative risk ration (RRR) to peanut allergy .(3) OTI also reduced egg allergy in the general population in a per protocol analysis.(1) These published RCT findings have changed practice and many governmental and allergy societies now recommend introducing peanut in infancy; some suggest that other foods, such as well-cooked egg, are also introduced. Only National Institute of Allergy and Infectious Diseases (NIAID) stratify their recommendations according to food allergy (FA) risk level.