Objective: Patients with primary Sjögren Disease (pSD) are prone to develop non-Hodgkin's lymphoma (NHL-pSD) but relevant biomarkers are lacking. We aimed to determine new biomarkers predictive of NHL in patients with pSD.
Methods: 206 pSD patients fulfilling ACR/EULAR 2016 criteria were included and divided into three groups: pSD, lymphoproliferative pSD (Arl-pSD), and NHL-pSD. Deep flow cytometry immunophenotyping of B and T cell compartments as well as serum IFNα quantification were coupled to clinical, biological and histopathological data analysis.
Results: We identified CD11c+FcRL5+ tissue-like memory B cells and IFNγ+TNFα+ conventional T cells as significantly associated with NHL in pSD. These clusters showed progressive enrichment in Arl-pSD and NHL-pSD as compared to pSD. The combination of these two populations abundances discriminates NHL-pSD patients with a sensitivity of 78.9% and a specificity of 76.8%, thus overcoming alone the performance of the sum of conventional clinical and biological markers such as cryoglobulinemia vasculitis, parotid enlargement, adapted clinESSDAI, RF antibodies, low C4 and elevated serum IFNα (68.4% and 78.0% respectively). CD11c+ FcRL5+ tissue-like memory B cells were associated with occurrence of mucosa-associated lymphoid tissue marginal-zone lymphoma (MALT NHL), while IFNγ+TNFα+ conventional T cells were more indicative of non-MALT B-cell NHLs.
Conclusion: We unveil novel biomarkers of NHL in pSD based on an integrative analysis coupling deep immunophenotyping and clinical, biological and histopathological data. Furthermore, these markers allow distinguishing B-cell NHL subtypes in pSD.
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