Premium
Prevalence and Characteristics of Persistent Clonal T Cell Large Granular Lymphocyte Expansions in Rheumatoid Arthritis
Author(s) -
Schwaneck Eva C.,
Renner Regina,
Junker Lara,
Einsele Hermann,
Gadeholt Ottar,
Geissinger Eva,
Kleinert Stefan,
Gernert Michael,
Tony HansPeter,
Schmalzing Marc
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40654
Subject(s) - rheumatoid arthritis , medicine , clone (java method) , immunology , lymphocyte , lymphoproliferative disorders , lymphoma , tumor necrosis factor alpha , t cell , methotrexate , gastroenterology , psoriasis , arthritis , flow cytometry , biology , immune system , dna , genetics
Objective Up to one‐third of patients with T cell large granular lymphocyte (T‐ LGL ) leukemia display symptoms of rheumatoid arthritis ( RA ). In Crohn's disease and psoriasis, treatment with tumor necrosis factor ( TNF ) inhibitors is associated with hepatosplenic γδ T cell lymphoma and with clonal expansion of γδ T cells, respectively. This study was undertaken to determine the prevalence of clonal T‐ LGL cells in patients with RA and define risk factors for this rare hematologic malignancy. Methods A total of 529 RA patients were recruited between November 2013 and August 2015. Eight‐color flow cytometry (fluorescence‐activated cell sorting [ FACS ]) was performed to screen for aberrant T cell populations of LGL s. Molecular analysis of the T cell receptor was used to confirm the diagnosis in patients with suggestive FACS findings. Electronic patient files were used to determine risk factors. Patients with clonal populations were monitored prospectively for up to 4 years. Results The median patient age was 61 years, and 74% were female. The median duration of RA was 12 years. The median Disease Activity Score in 28 joints was 2.8, and 69.9% of patients had ever been treated with biologic disease‐modifying antirheumatic drugs. We identified clonal T‐ LGL expansions in 19 patients, equaling a prevalence of 3.6%. The T‐ LGL cell clone was constant over time in most patients and was significantly associated with the duration of the exposure to TNF ‐blocking agents ( P = 0.01). No other risk factors could be detected. Conclusion RA patients with long‐term exposure to TNF ‐blocking agents were at a greater risk of developing clonal expansions of LGL s. This finding may prompt clinicians to refrain from using these substances in RA patients with known T cell aberrations.