Background/Purpose:  The IL-23 axis and Th17 type
immunity has been implicated in the pathogenesis  of Ankylosing Spondylitis (AS)
and an enrichment of gamma delta (gd) T
cells expressing IL-23R in AS patients has previously been reported (Kenna et
al Arthritis Rheum. 2012).  However, the relationship of these cells with
clinical phenotype remains to be determined.  We aimed to deepen the understanding
of the relationship between the IL-23 axis, gd
T cells and clinical phenotype in the immunopathogenesis of axial
spondyloarthritis (axSpA) by examining cellular expression of IL-23 axis
molecules on gd T cells in peripheral
blood of highly active biologic naïve AS subjects.

Methods: Thirty nine patients diagnosed with active
AS meeting ASAS criteria with sacroiliitis by imaging were recruited to a
longitudinal observational study and phenotypically characterized using disease
activity (ASDAS-CRP), radiographic vs. MRI only imaging changes, HLAB27,
extraspinal features and medication use in first 6 months. Peripheral blood was
obtained at baseline and multicolor flow cytometry performed to determine the
expression of IL-23R and the IL-23 axis molecule CCR6 on gd T cells relative to healthy volunteer (HV)
controls (n=20) .

Results: Of the 39 patients studied, 18 (46%) were
male, mean (SD) age was 41.7 (15.3), symptom duration 9.6 (8.3) yrs, 15 (38%)
were HLA-B27+, CRP (1.5 (1.4) mg/dl and ASDAS-CRP 2.7 (0.7).  11 (52%) of those
with follow-up  started TNFi therapy within 6  months. All had confirmed
sacroiliitis, 15 (38%) by radiographs (rad), 18 (46%) by MRI (non-rad) sacroiliitis,
and 6 (15%) by both. There were no significant clinical differences between
sexes or those with radiographic/MRI findings.  Similar to previously published
studies, an increase in the % gd TCR+
cells was observed in SPA subjects vs control.  Moreover, analysis of CCR6
expression on the gd subset
demonstrated that 61.5% of SpA patients showed increased levels (mean % ± 2 s.d
vs. HV) of CCR6+, gd + T cells in peripheral
blood (CCR6 Hi) while 38.5% of the subjects were similar to HV controls (CCR6 Lo). 
The percentage of IL-23R+, gd T cells
was also significantly increased in CCR6hi patients vs. CCR6lo patients (Table 1). 
Also, a correlation between the density of IL-23R and % CCR6+ gd cells in the SpA subjects was observed (r
= 0.422, p=0.0074).  Analysis of ASDAS-CRP scores showed that within the CCR6 Hi,
gd subjects, 21% of the patients
demonstrated severe disease (score >3.5) versus 6.6% in the CCR6 Lo group. 
Also, a trend towards increased CCR6 receptor expression on gd cells and severity of ASDAS-CRP was seen
in CCR6 Hi subjects (r = 0.43)

* Molecules
of Equivalent Soluble Fluorochrome 

Conclusion: These data sugg est that CCR6+, IL-23R+ gd T cells play a role in more active AS. 
Further understanding of how these cells contribute to the disease phenotype
may lead to improved strategies for patient selection and treatment approaches
for AS.