Spread of clonal T-cell expansions in rheumatoid arthritis patients

Despite a large number of studies identifying expanded T-cell clones among infiltrating lymphocytes, little is known about their distribution in patients suffering from rheumatoid arthritis. To evaluate the clonality of alpha/beta T-cell populations in arthritic locations and PBL, we determined the CDR3 size lengths of TCR beta-chain transcripts using BV (Vbeta), BC (Cbeta), BJ (Jbeta), and clonotype-specific primers. Transcripts from PBL of healthy donors show gaussian profiles of approximately eight CDR3 size peaks in most BV subfamilies. Dominant peaks standing out above the normal background identify expansions of one or several T-cell clones within a given BV subfamily. The analysis of six patients suffering from rheumatoid arthritis showed clonal expansions in all samples including PBL. Synovial tissue infiltrates revealed less complex repertoires with a greater number of expanded clones than PBL. Expanded clones varied from one patient to another; no recurrences were observed. Most interestingly, identical clones were identified bilaterally in arthritic knee joints and PBL from the same patient. Our data show that given T-cell clones are not only locally expanded but can also be found in the periphery, and strongly suggest that many similar clones spread throughout the bodies of patients.