Background/Purpose: Oligoarticular juvenile idiopathic arthritis (oligo JIA) is characterized by arthritis in a few joints (fewer than 5) with recurrent flares of inflammation, often in the same joint distribution.  The mechanisms driving site-specific inflammation in oligo JIA remain unknown.  Previous evaluations of the T cell receptor beta (TCRB) repertoire in oligo JIA patients revealed clonotypic expansion among CD4⁺ effector and regulatory T cell populations obtained from the synovial fluid (SF).  We aimed to further delineate the dynamics of the T cell repertoire in the arthritic joints of oligo JIA patients longitudinally.

Methods: SF samples were collected from 3 oligo JIA patients, defined by ILAR criteria, at 2 timepoints.  Serial samples were taken from the same affected joint in a given patient.  Peripheral blood (PB) from 7 healthy donors was also collected.  DNA was extracted from sorted regulatory (CD4⁺CD25⁺CD127^lo, Treg), effector (CD4⁺CD25^–, Teff), and CD8⁺ T cells.  The TCRB complementarity determining region 3 (CDR3) was amplified by multiplex PCR and sequenced using the Illumina HiSeq platform (Adaptive Biotechnologies).  Data was analyzed with VDJtools 1.2.1 and R 3.5.1.

Results: 3 oligo JIA patients (1 male and 2 females) with an average age of 6.4 years were studied.  SF was collected from the knee joint in all cases.  At baseline (T1), no patient was treated with immunosuppressive medications; however, at the second timepoint (T2), all were taking disease-modifying antirheumatic drugs.  The SF sample at T2 was on average 17.3 months after the sample at T1.  The SF Treg, Teff, and CD8⁺ TCRB repertoires were more clonal than those of the respective T cell population in the PB of controls.  There was no substantial variation over time in the clonality of Treg, Teff, and CD8⁺ T cell populations from serial SF samples.  In an individual patient, there was overlap in the amino acid sequences of the TCRB CDR3 at T1 and T2: on average, 18%, 19% and 8% of the clonotypes were the same at T1 and T2, respectively for Treg, Teff, and CD8⁺ T cell repertoires.  TCR clones that reoccurred over time tended to be more clonally expanded than TCR clones that occurred at only one timepoint, with frequencies of shared clones being 2-, 3-, and 5-fold larger on average, respectively in Treg, Teff and CD8+ T cells.  Sharing of clones across patients was identified more frequently in Treg and CD8⁺ T cell than Teff cells.

Conclusion: Flares of arthritis in oligo JIA were characterized by resurgence of the same TCR clones longitudinally.  There was also sharing of TCR clonotypes in Treg and CD8⁺ T cells across oligo JIA patients.  These findings suggest that pathogenic clones, potentially recognizing similar antigens, may persist in the joints of oligo JIA patients and drive disease over time.  While recurring clones may be recruited to the joint with each flare, the extent of repertoire overlap suggests a resident phenotype.  Further work is ongoing to characterize the physicochemical properties of shared and clonally expanded clones, and to determine whether they are resident in the affected joints.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identical-t-cell-clones-identified-over-time-in-the-joints-of-oligoarticular-juvenile-idiopathic-arthritis-patients/