AT-001 / Theriva Bio - LARVOL DELTA

Autoimmune reactive synovium CD4+HLADR+ T effectors with regulatory resistance and inflammatory potential in human arthritis (EULAR 2025) - "Additionally, autoimmune reactivity of CD4 + HLADR + T cells towards the dnaJP1 peptide was demonstrated in adult rheumatic disease individuals, indicating their disease relevance in adult populations... CD4 + HLADR + T effectors were expanded and highly inflammatory within the synovium compartment. Notably, CD4 + HLADR + Tregs demonstrated strong transcriptomic convergence and TCR clonatype sharing with their analogous HLADR + effectors, indicating a common disease origin. While CD4 + HLADR + Tregs were lineage stable and capable of suppression, CD4 + HLADR + effectors could circumvent regulatory control and elicit an independent inflammatory response to disease relevant antigens."

Idiopathic Arthritis • Immunology • Rheumatology • CD4 • FOXP3 • HSPD1 • IFNG • IL21

Circulating Pathogenic Like Lymphocytes Are Mechanistic Targets for the Induction of Immune Tolerance in Rheumatoid Arthritis (FOCIS 2024) - "In summary, our data identifies in dnaJP1-specific CPL a mechanistic target of clinical relevant immune toleration. It also identifies CPL as an easily accessible pool of pathogenic-like cells, which may be used to advance our understanding of aberrant self-recognition, as well as to design targeted diagnostic and therapeutic tools."

Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD4 • IFNG • IL17A • TNFA

CIRCULATING PATHOGENIC LIKE LYMPHOCYTES ARE MECHANISTIC TARGETS FOR THE TOLEROGENIC RE-EDUCATION IN RHEUMATOID ARTHRITIC PATIENTS (EULAR 2024) - "Separately, we have demonstrated that mucosal tolerance re-education with the heat shock protein derived peptide, dnaJP1, has shown promising synergistic potentiation with hydroxycholorquine (P = 0.009 in ACR20 score) in a phase 2 trial with rheumatoid arthritic (RA) patients[2]. Overall, through the application of the high parametric technological platform, CyToF, we have demonstrated the enriched memory presence of a systemic population of inflammatory pathogenic T cells, CPLs. More importantly, CPLs elicited antigenic memory response in the presence of dnaJP1, unveiling a new mechanism through which aberrant self recognition could occur. This study identifies, CPLs, as an accessible pool of pathogenic-like T cells that could be used to advance our understanding of autoimmunity, and aid in designing diagnostic and therapeutic tools for RA."

Clinical • Immunology • Rheumatoid Arthritis • CD4 • CD69 • IFNG • IL17A • TNFA

DYNAMIC INTERPLAY OF FUNCTIONALLY DISCORDANT CD4+HLA-DR+ SUBSETS WITH A COMMON PATHOLOGICAL ONTOGENIC ORIGIN IN HUMAN ARTHRITIS (EULAR 2023) - "Importantly, CPLs/iaTregs from RA patients demonstrated reactivity to the dnaJP1 peptide, which is a pro-inflammatory epitope in RA patients, thus underscoring disease relevance...Conclusion Our study highlights the disease relevance of CPLs/iaTregs in human arthritis, whilst revealing evidence of a common pathological ontogeny for CPLs/iaTregs, that is antigenically driven by the inflammatory synovium environment. The dynamic interplay between CPLs/iaTregs, could be titled towards suppression evasion through IFNg, allowing for continual synovium inflammation."

Discordant • Idiopathic Arthritis • Immunology • Inflammation • Pediatrics • Rheumatology • CD4 • FOXP3 • IFNG