Early detection of extranodal marginal zone lymphoma in Sjögren's syndrome patients through immunogenetics

ABSTRACT: Activated B cells play a key role in the pathogenesis of Sjögren’s syndrome (SjS) through the production of autoantibodies and the development of ectopic germinal centers in the salivary glands and other affected sites. Around 5-10% of SjS patients develop B-cell lymphoma, usually extranodal marginal zone lymphomas (eMZL) of the mucosa-associated lymphoid tissue (MALT). The aim of the current study is to screen for the eMZL clonotype in prediagnostic blood and tissue biopsies of SjS patients. We studied prediagnostic tissue biopsies of 3 SjS patients diagnosed with eMZL through immunoglobulin (IG) gene repertoire sequencing. In all 3 cases, we observed the eMZL clonotype in prediagnostic tissue biopsies. To evaluate if skewing in the IGH repertoire may also be detected in the peripheral blood, we sequenced a peripheral blood mononuclear cell (PBMC) sample drawn at eMZL diagnosis and 2 years prior to eMZL relapse in two SjS patients. The eMZL clonotype was detected in the peripheral blood prior to diagnosis for both cases. Next, we selected 3 SjS patients who developed eMZL lymphoma and 3 additional SjS patients who remained cancer-free. We sequenced the IG heavy chain (IGH) gene repertoire in PBMC samples taken a median of 3 years before eMZL diagnosis. In 2 out of 3 eMZL patients, the dominant clonotype in the prediagnostic PBMC samples matched the eMZL clonotype in the diagnostic biopsy. The eMZL clonotypes observed utilized stereotypic IGHV gene combinations (IGHV1-69/IGHJ4 and IGHV4-59/IGHJ5) associated with rheumatoid factor activity, a previously reported feature of eMZL in SjS. Notably, no significant abnormalities were observed in the IGH gene repertoire of the controls. In conclusion, our results indicate that immunogenetic sequencing of the IGH gene repertoire may be an effective method of early detection of eMZL in SjS patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221412 | GEO | 2023/04/12

REPOSITORIES: GEO