ALTO: From Autoimmunity to Lymphoma: To unravel lymphomagenesis in primary Sjögren disease


Sjögren disease (Sjo) is a prototypic systemic autoimmune disease (AID) characterized by lymphoid infiltration of lachrymal and salivary glands leading to xerophtalmia and xerostomia, as well as polyclonal B-cell activation and systemic complications. Sjo is the AID with the highest risk of lymphoma with an increased risk of 10 to 15 fold compared to the general population. Progression from autoimmunity towards B cell lymphoma in Sjo is a multistep process. Our hypothesis is that the occurrence of lymphoma in Sjo results from hyperactivation of B cells, notably of auto-reactive rheumatoid factor (RF) B cells, and from defective immunosurveillance.

Facts and Figures

Project Lead
MD, PhD Gaetane Nocturne
Paris-Saclay University – INSERM U1184
FOREUM research grant: € 200.000

Meet the Team

Project Lead

MD, PhD Gaetane Nocturne
Paris-Saclay University – INSERM U1184


The objective of this project is to better understand how autoimmune B cell become lymphomatous by focusing on:

  • The role of genetic abnormalities: we will assess if accumulation of germline variants could promote NF-kB activation and thus escape of autoimmune RF B cells continuously stimulated by immune complexes.
  • The role of BCR stimulation: we will focus on BCR bearing RF activity and we will track RF clonotypes in Sjo patients with lymphoma.
  • The role of immunosurveillance: we will describe actors of immunosurveillance within salivary glands in Sjo patients with and without lymphoma.


  • Milestone 1: To assess NF-kB activation (canonical and non-canonical pathways) depending on the WES signature.
  • Milestone 2: To synthetize mutated and unmated RF and to test their binding affinity to IC
  • Milestone 3: To obtain the first atlas at molecular scale and spatially resolved of microenvironment before and at the time of lymphoma in Sjo patients.

Patient Voice

The occurrence of lymphoma is a dreaded complication of Sjo. It is essential to progress in the understanding of the mechanisms at the origin of its emergence in order to identify early the patients at risk and to adapt their management. Since the beginning of our research work, our results have been shared with patients via patient associations. We are working with Sjogren Europe, a patients association born with the support of EULAR, to disseminate the results and their potential implication in clinical practice by writing lay articles in the association's newsletters and interventions at their general meetings. We will continue this close collaboration with the Sjogren Europe association represented by Mrs Coralie Bouillot and Mrs Joyce Koelewijn-Tukker in order to work on the dissemination of the results obtained through this project so that all patients can benefit from them.

Project Map