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Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients
Autoimmunity, 08/10/09

Mamedov IZ et al. – These findings indicate that either acute or chronic viral infection could trigger some of the stable T cell expansions observed in ankylosing spondylitis (AS) patients. Though participation of these T cell clones in development of the disease remains unclear, their highly differentiated status makes these clones potentially pro-inflammatory, and supposes that they could participate in autoimmune reactions.

• Study aims to understand the nature and behavior of expanded T cell clones in AS pts by monitoring their stable abundance in 1.5- and 2.5-yrs studies and their individual characterization
• Mass sequencing of TCR V beta libraries was performed to search for the expanded T cell clones for 2 AS pts

• A no. of clones comprising > 5% of the corresponding TCR V beta family were identified in both pts
• These expanded clones were stably abundant in blood samples of AS pts for the prolonged period (1.5 and 2.5 yrs)
• These clones were individually characterized for their differentiation status using FACS with CD27, CD28, and CD45RA markers
• This was followed by quantitative identification of each clone within corresponding fraction using RT-PCR analysis
• Stable clones differed in phenotype and several belonged to the proinflammatory CD27 - /CD28 – population
• Their potentially cytotoxic status was confirmed by staining with perforin-specific Abs
• Search for the TCR V beta CRD3 sequences homologous to the identified clones revealed close matches with the previously reported T cell clones from AS and reactive arthritis pts
• Thus supporting their role in the disease and proposing consensus TCR V beta CDR3 motifs for AS
• Interestingly, these motifs were also found to have homology with earlier reported virus-specific CDR3 variants, indicating that viral infections could play role in development of AS

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