Abstract
Objectives Approximately 15% of patients with T-cell large granular lymphocytic leukemia (T-LGLL) have rheumatoid arthritis (RA). RA-associated T-LGLL with low large granular lymphocyte counts (aleukemic presentation) and Felty's syndrome (FS) have indistinguishable clinical presentations. These disorders are distinguished by T-cell clonality which is observed in T-LGLL but not in FS. Activating somatic mutations in the signal transducer and activator of transcription 3 (STAT3) and 5 (STAT5b) genes are involved in T-LGLL pathogenesis; however, the prevalence of these mutations in FS is unknown.Methods Based on the rearrangements of T-cell receptor (TCR) gamma and beta genes according to the BIOMED-2 protocol, we examined T-cell clonality in 81 patients with RA and unexplained neutropenia. We stratified these patients by the presence or absence of T-cell clonality, respectively, into 2 groups: RA-associated T-LGLL (56 patients) and FS (25 patients). Allele-specific TaqMan Real-Time polymerase chain reaction assay was employed to detect point somatic mutations in STAT3 and STAT5b genes in each group.Results Mutations of the STAT3 gene were detected in none of the 24 cases of FS and in 22 of 56 cases of RA-associated T-LGLL (39%) (p < 0.001). No mutation of the STAT5b gene was detected in any of the patients in each group.Conclusions Although further data are needed, our results suggest that activating somatic mutations in STAT3 and STAT5b genes are not involved in the pathogenesis of FS.
Case report: response in proteinuria due to AA amyloidosis but not Felty's syndrome in a patient with rheumatoid arthritis treated with TNF- blockade