Background/Purpose: IL-23 may play a key role in the pathogenesis of ankylosing spondylitis (AS).  Some studies describe indeed increased serum levels of IL-23 in AS patients compared to healthy controls [1-3]. Recent evidence also shows enhanced IL-23 production in the gut of AS patients. This upregulation of IL-23 expression in the gut seems to be the result of activation of autophagy rather than of an activated unfolded protein response [4].  We investigated IL-23 expression and the role of autophagy ex vivo in the synovium and peripheral blood mononuclear cells (PBMCs) of HLA-B27 positive AS patients.

Methods: Synovial tissues were obtained by needle arthroscopy from actively inflamed knees from patients with AS (HLA-B27 positive; n=11), other forms of spondyloarthritis (SpA) (HLA-B27 positive; n=9 or HLA-B27 negative; n=10), rheumatoid arthritis (RA) (HLA-B27 positive or negative; n=10) or other inflammatory joint diseases (‘non SpA/RA inflammatory joint disease’) (HLA-B27 positive or negative; n=10)) and from multiple organ donors as non-inflammatory controls (HLA-B27 negative; n=10). PBMCs were isolated from whole blood samples taken from patients with AS (HLA-B27 positive; n=17), RA (HLA-B27 negative; n=19) and healthy controls (HLA-B27 negative; n=12). None of the patients was treated with TNF inhibitors. Expression of IL-23 and autophagy genes in all samples was analyzed using quantitative RT-PCR (SYBR green) with primers for IL23p19 and autophagy genes (ATG16L1, IRGM, MAP1LC3A, ATG5, HSPA8 and HSP90AA1).

Results:  In the synovial tissues, IL-23p19 expression was consistently increased in the inflammatory samples compared to the non-inflammatory samples. There was no difference in IL-23p19 expression in AS patients as compared to non-AS SpA and other inflammatory diseases. In PBMCs, surprisingly, the expression of IL-23p19 was significantly lower in AS patients than in healthy controls with expression levels in RA patients extending over the whole range between AS patients and controls. No difference in expression of autophagy associated genes was found in the synovial tissues between the groups. In the PBMCs, there was a lower expression of ATG16L1, IRGM and HSP90AA1 in AS patients compared to healthy controls. The expression of MAP1LC3A, ATG5 and HSPA8was not statistically different between the three groups.

Conclusion: Notwithstanding the recent evidence in gut samples of AS patients, our data do not support evidence for higher IL-23 expression and activation of autophagy in synovium or PBMCs of HLA-B27 positive AS patients.  The production of IL-23, possibly driven by autophagy, in AS patients seems to be a tissue specific phenomenon with an important role reserved for the gut.

References:

1. Mei Y et al. Clin Rheumatol. 2011; 30: 269–273.
2. Wang X, Lin Z, Wei Q, Jiang Y & Gu J.  Rheumatol Int. 2009; 29: 1343–1347.
3. Andersen T et al. Rheumatol Int. 2012; 32: 387-393.
4. Ciccia F et al. Ann Rheum Dis. 2013 Jun 5. [Epub ahead of print]

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-23-expression-and-activation-of-autophagy-in-synovium-and-pbmcs-of-hla-b27-positive-patients-with-ankylosing-spondylitis/