IL-17A and IL-6 are highly expressed in SLE SF
First, we wanted to investigate T-cell associated cytokines in SF of SLE
patients. Thus, SF from SLE patients (n=17) were tested for cytokine
content in comparison to paired serum samples (n=14) and SF from RA
patients (n=10), matched for storage time (Supplementary Table S2). In
SLE, IL-17A was detected in SF (44.9 pg/ml (10.7 - 405.2)) and matched
serum (37.5 pg/ml (22.4 - 94.2)) (Fig. 1A), although no statistically
significant difference was shown (p=0.4 ).
IL-6 was significantly higher in SLE-SF (771 pg/ml (108.5-2135)) as
compared to corresponding serum samples (1.7 pg/ml (1.2-4.9),p=0.0006 ). Low concentrations of IL-10 could be detected in 41%
of SLE SF samples (0 pg/ml (0-3.4)) and was higher in serum (0.29 pg/ml
(0.1-0.4)). Overall, the RA SF samples displayed similar ranges of
cytokines as SLE SF, with higher median values of IL-6 (3627 pg/ml
(334.6-5000), p=0.11) and IL-10 (1.9 pg/ml (0-7.9), p=0.19) and less
IL-17A, (0 pg/ml (0-172), p=0.11) however without statistical
significance (Fig. 1A). The cytokine levels did not differ between SLE
patients with and without secondary osteoarthritis (data not shown).
Next, we explored the relationship of cytokine levels, in and between
compartments (Fig. 1B-C). In SLE SF, the levels of IL-6 correlated with
those of IL-10 (r=0.84, p=<0.0001 , CI=0.69-0.92) and,
weakly, with IL-17A (r=0.39, p=0.03 , CI=0.02-0.66) (Fig. 1B).
Also, IL-10 and IL-17A correlated weakly (r=0.43, p=0.01 ,
CI=0.07-0.69). When comparing serum and SF, levels of IL-6 correlated(r=0.7, p=0.0001) but neither IL-17A nor IL-10 (Fig. 1C).
Cytokine analyses included also IFN-γ, TNF, IL-2 and IL-4. In sera, IL-4
and IL-2 were higher compared to SF, however their concentrations were
consistently low (Supplementary Fig. 1A). Very low levels of IFN-γ could
be detected in SF of four SLE patients. TNF levels were below the
detection limit in all samples (Supplementary Fig. 2B).
Subsequently, we investigated the presence of IgA and IgM RF in serum
and SF. These did not correlate with the cytokine levels nor with other
autoantibodies (data not shown). Interestingly, the concentration of RF,
when present, was mostly higher in serum compared to SF (Fig. 1D).
For one SLE patient, SF samples from six timepoints were available, the
first obtained approximately 15 years after disease onset. This patient
presented with a recurrent polyarthritis, but no evidence of secondary
OA could be tracked in the clinical records. High IL-6 levels were
repeatedly measured over a 10 years period, while IL-17A levels
fluctuated and IL-10 concentrations were low (Fig. 2A).