Blood monocyte heterogeneity and markers of endothelial activation in ankylosing spondylitis.
OBJECTIVE
Ankylosing spondylitis (AS) is associated with excessive cardiovascular (CV) morbidity. Interactions between activated endothelium and monocytes precede atherosclerotic plaques. Our aim was to quantify blood monocyte subsets in relation to endothelial activation and inflammatory activity in subjects with AS who were free of clinical atherosclerotic CV disease.


METHODS
Markers of inflammation and endothelial activation were measured in 47 patients with AS receiving no disease-modifying antirheumatic drugs, and 22 healthy controls. Exclusion criteria included atherosclerotic CV disease and traditional risk factors. Flow cytometry was used to identify monocyte subsets: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+), and nonclassical CD14(+)CD16(++) monocytes and to evaluate their expression of CD11b and CD11c.


RESULTS
Traditional risk factors were comparable among the groups, except for lower high-density lipoprotein cholesterol in AS (p = 0.007). Relative to controls, in subjects with AS counts of classical monocytes were higher (84.3 ± 5.4 vs 78.9 ± 5.3% of blood monocytes, p < 0.001) and nonclassical monocytes lower (2.9 ± 2.2 vs 5.5 ± 2.3%, p < 0.001). In AS we observed increased soluble intercellular adhesion molecule-1 [251 (224-293) vs 202 (187-230) ng/ml, p = 0.002], an endothelial ligand for monocytic β2-integrin CD11b/CD18. CD11b expression on all 3 monocyte subsets was elevated in 21 AS subjects with a Bath Ankylosing Spondylitis Disease Activity Index score ≥ 4 versus the remaining patients (p = 0.005-0.03). C-reactive protein, interleukin 6 (IL-6), and pentraxin-3 were increased in AS, in contrast to tumor necrosis factor-α and IL-18. IL-6 correlated with classical monocytes numbers in AS (r = 0.56, p < 0.0001) but not in the controls (r = 0.10, p = 0.65).


CONCLUSIONS
Our findings suggest a contribution of immune dysregulation to enhanced monocyte-endothelial interactions in AS, especially in patients with active disease, which possibly can accelerate atherogenesis on a longterm basis.
From the Second Department of Cardiology, the Department of Rheumatology and Balneology, the Division of Rheumatology, Department of Internal Medicine and Gerontology, and the Department of Internal and Agricultural Medicine, Jagiellonian University Medical College and University Hospital; and J. Dietl Hospital, Krakow, Poland.
Andrzej
A
Surdacki
Joanna
J
Sulicka
Mariusz
M
Korkosz
Tomasz
T
Mikolajczyk
Dorota
D
Telesinska-Jasiówka
Ewa
E
Klimek
Izabella
I
Kierzkowska
Tomasz
T
Guzik
Tomasz K
TK
Grodzicki
D000328:Adult; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification / Q000378:metabolism*; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000473:pathology; D055815:Young Adult
D015415:Biomarkers
ANKYLOSING SPONDYLITIS; ENDOTHELIUM; MONOCYTES