Rheumatology Medical News about Ankylosing spondylitis, T cell, TCR

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Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients
Autoimmunity, 08/12/09

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.

Methods

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

Results

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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