The "Autoimmune Diseases" Laboratory (LMA) within the IDMIT Department, located on the Bicêtre Hospital Campus, focuses on the immunopathology of rheumatoid arthritis (RA), Sjögren’s disease (SjD), and neuroinflammation in children. The team also investigates the links between autoimmunity and cancer, particularly the mechanisms driving lymphoma development in patients with autoimmune diseases.
🔬 Research Areas
Rheumatoid Arthritis (RA)
The LMA team has developed a non-human primate model of RA. Research focuses on the molecular bases of immunogenicity to therapeutic monoclonal antibodies by identifying CD4+ T cell epitopes. The aim is to elucidate the mechanisms of action of methotrexate in reducing the immunogenicity of biologic treatments for RA. Using a transgenic BAFF mouse model, the team demonstrated an interaction between BAFF cytokine and methotrexate that favors the induction of regulatory B cells (Bregs) and immune tolerance. Ongoing research addresses immunogenic responses to rituximab.
Additionally, the team has shown that RA patients exhibit impaired polarization of circulating monocytes toward anti-inflammatory macrophages, associated with overexpression of microRNA-155. While inhibition of this microRNA via pegylated liposomal delivery has yielded promising results in murine models, clinical application remains challenging. The team hypothesizes that this dysregulation is linked to altered immunometabolism, as metabolic differences between pro- and anti-inflammatory macrophages influence their polarization. The objective is to characterize the metabolomic profile of RA patient monocytes/macrophages to identify novel therapeutic targets.
Sjögren’s Disease (SjD)
The LMA team is an international leader in the study of SjD immunopathology. They have demonstrated the presence of a characteristic interferon (IFN) signature in the disease. Research also investigates chronic B cell activation, highlighting the role of the IFN/BAFF axis and the lympho-epithelial crosstalk in disease progression. The team is developing immune organoids as innovative models to study SjD. A cutting-edge research direction involves epitranscriptomics, where the team has shown that dysregulation of post-transcriptional modifications contributes to the IFN signature in SjD.
New B Cell–Targeted Therapies
Sjögren’s disease is the paradigm of autoimmune diseases driven by B cell activation. The team is involved in the development of new treatments leading to total B cell depletion: anti-CD19 CAR-T cells or bispecific CD3/CD19 T-cell engagers. Thanks to a collaboration with the Gustave Roussy Institute, academic CAR-T cells may be offered to patients with refractory autoimmune diseases.
The team is also investigating, in a SjD model, the possibility of using CAR-T cells specific to autoreactive B cells to selectively eliminate them and induce significantly improved immune tolerance.
Lymphomas Associated with Autoimmune Diseases
In the context of lymphomas complicating autoimmune diseases, the team aims to identify molecular and genetic abnormalities (somatic and germline) associated with an increased risk of lymphoma in SjD patients. They have demonstrated the role of mutations in the TNFAIP3 gene, which encodes A20, a key regulator of NF-κB signaling. Ongoing work investigates the multi-step transformation of rheumatoid factor-positive autoreactive B cell clones.
Link Between Cancer and Autoimmunity
Some treatments for autoimmune diseases, such as rituximab, were initially developed in oncology. This therapeutic convergence continues today with the emerging use of CAR-T cells and bispecific antibodies targeting B lymphocytes in autoimmune diseases. Conversely, certain cancer treatments—particularly immune checkpoint inhibitors—can induce inflammatory side effects similar to autoimmune disorders. Anti-cytokine therapies (anti-IL-6, anti-TNF), originally developed in rheumatology, have proven effective in such cases.
In this context, the team is studying the effects of JAK inhibitors (JAKi), used in rheumatoid arthritis, on antitumor immune surveillance. After demonstrating that certain JAK inhibitors impair natural killer (NK) cell function, the team is now exploring their impact on macrophages, key players in the tumor microenvironment. Specifically, they are investigating how these treatments influence the polarization of monocytes into macrophages and modulate their antitumor functions.
Studying the links between cancer and autoimmune diseases is essential for improving the care of patients affected by both types of conditions. This research theme was recognized and awarded in both 2020 and 2024 by the FHU CARE 2 initiative (https://fhucare.com/fr/).
Neuroinflammation in Children
In the field of neuroimmune disorders, the team pursues three main objectives: 1- to elucidate the immunological mechanisms involved in disease onset ; 2 - to identify relevant biomarkers : 3 - to explore novel therapeutic approaches.
Regarding anti-NMDAR encephalitis, the team has established a correlation between clinical severity and levels of multiple biomarkers, including neurofilament light chain (NfL), GFAP, and Tau protein. Recent studies on MOG antibody-associated disorders (MOGAD) revealed an increase in regulatory T cells in non-relapsing patients (MOGNR), a phenomenon absent in relapsing cases (MOGR). Interestingly, baseline NfL levels were paradoxically higher in MOGNR patients compared to MOGR patients.
In collaboration with the MIRCEN Department of the François Jacob Institute of Biology, the team developed an experimental autoimmune encephalitis model in non-human primates, induced by injection of human MOG protein. This model closely replicates MOGAD features and revealed that anti-MOG antibodies persist despite effective treatment, although they are present and capable of complement activation at disease onset. Several innovative therapeutic projects are currently underway based on this promising animal model.