B-Cell Stimulating Factors among patients with primary Sjögren's syndrome linked to lymphoma development

A new study by Pierre-Marie Duret and team showed that prior to developing cancer, primary Sjögren's syndrome (pSS) patients' peripheral blood had elevated levels of Bruton's tyrosine kinase (BTK) and a proliferation-inducing ligand (APRIL). The findings of this study were published in Arthritis and Rheumatology  and was carried out to examine the expression of B-cell genes in primary Sjögren's syndrome-related lymphoma (pSS-NHL) and to study whole blood gene expression.

From the 345 well-phenotyped pSS patients enrolled in the prospective ASSESS cohort, peripheral whole blood samples were taken. Using Clariom S Human Arrays from Affymetrix, transcriptomic analysis was carried out. Patients with incident lymphoma (i-pSS-NHL) were used as the case group in the primary analysis, while all patients without lymphoma were used as the comparison group. All-pSS-NHL, including those with a history of lymphoma (h-pSS-NHL), were used as the case group in sensitivity analyses, and patients without lymphoma were examined in relation to their risk factors for lymphoma.

The key findings of this study were:

1. In all, 21 pSS-NHL patients (8 i-pSS-NHL and 13 h-pSS-NHL) who were qualified for transcriptome analysis were compared to 324 pSS controls who did not have lymphoma, including 61 without a risk factor for lymphoma and 110 with moderate to severe disease activity.

2. Genes involved in innate and adaptive immunity, especially those associated with B cells, were shown to be enriched, according to functional clustering studies.

3. In contrast to individuals without lymphoma, patients with incident lymphoma had overexpressed Bruton's tyrosine kinase and a proliferation-inducing ligand genes prior to the development of the disease.

4. BTK was consistently increased in sensitivity analyses across all contrasts used. On multivariate analyses using 9 validated lymphoma predictors in pSS, BTK expression was linked to risk of lymphoma.

Patients with primary Sjögren's illness who later developed cancer had overexpressed Bruton's tyrosine kinase and the cytokine APRIL, according to genetic blood testing. It is necessary to confirm the relationship between BTK, APRIL, and pSS-NHL in other prospective cohorts.

Reference: 

Duret, P., Schleiss, C., Kawka, L., Meyer, N., Ye, T., Saraux, A., Devauchelle‐Pensec, V., Seror, R., Larroche, C., Perdriger, A., Sibilia, J., Vallat, L., Fornecker, L., Nocturne, G., Mariette, X., & Gottenberg, J. (2023). Bruton’s tyrosine kinase (BTK) gene overexpression is associated with risk of lymphoma in primary Sjögren’s syndrome. In Arthritis & Rheumatology. Wiley. https://doi.org/10.1002/art.42550