Background/Purpose

Spondyloarthritis (SpA) is characterized by aseptic inflammation of the axial skeleton which may ultimately lead to irreversible deformities due to bony ankylosis. Occasionally, peripheral joints and extraskeletal sites are also involved. The etiology is unknown, but there is a well-established association with HLA-B27. Intervertebral discs and diarthrodial joints of the spine are targeted by the disease, and studies on cartilage have indicated increased turnover of several extracellular matrix components, mainly collagen, in active ankylosing spondylitis (AS). Thus, C2M, a matrix metalloproteinase derived collagen type II fragment has been found to be increased in AS. Procollagen IIA, an alternatively spliced collagen II variant, is preferentially expressed during embryogenic skeletal patterning where it is supposed to participate in the regulation of chondro- and osteogenesis. In adults PIIANP is present in damaged cartilage and osteophytes.

The aims of this investigation were to assess collagen II turnover in SpA by studying C2M and PIIANP concomitantly in patients treated with or without TNF inhibitors (TNFi).

Methods

One hundred and ten patients (age 18-63 years) with SpA according to the ASAS criteria were recruited from two secondary and one tertiary center. Demographic and clinical disease measures were recorded. Ninety six volunteer blood donors served as healthy controls. C2M and PIIANP were quantified in serum by ELISA. Mann–Whitney U test for intergroup comparisons and Spearman’s rank test for correlations were applied. The discriminative power of the serum markers between healthy and diseased was calculated by receiver-operator characteristics (ROC) and expressed by the area under the curve (AUC).

Results

The serum level of C2M was higher in SpA patients compared to healthy controls (p<0.01)(table). The PIIANP level did not differ between SpA patients and controls. There was no correlation between C2M and PIIANP. C2M correlated negatively with smoking (r=-0.22;p=0.02) and PIIANP correlated positively with sex (r=0.31;p=0.001), CRP (r=0.31;p=0.001), HLA-B27 (r=0.21;p=0.03) and negatively with treatment (r=-0.23;p=0.02). Patients were categorized according to TNFi treatment (TNFi-/TNFi+). PIIANP and C2M were increased in TNFi- patients compared to controls (p<0.05-0.001). Using ROC calculation for C2M AUC was estimated to 0.67.

 

Characteristics	SpA (n=110)	TNFi- (n=57)	TNFi+ (n=53)
Sex (% male)	72%	63%*	81%
Age	36.6 (35.3-38.0)	35.7 (33.4-37.9)	37.7(36.1-39.3)
BMI	25.5 (24.8-26.3)	25.4 (24.1-26.6)	25.7 (24.8-26.6)
Smoker	36%	32%	42%
HLA-B27 (%)	87%	84%	91%
Disease duration (y)	6.4 (5.4-7.5)	5.0 (3.7-6.3)**	8.1 (6.4-9.7)
Patient global VAS	34 (29-39)	43 (35-50)**	25.8 (19.3-32.3)
Patient pain VAS	32 (27-37)	40 (33-48)***	23.4 (17.4-29.4)
Patient fatigue VAS	40 (34-45)	48 (40-55)**	32.8 (25.7-39.9)
Physician global VAS	4 (1;16)	10 (1;24)***	1 (0;7)
BASDAI	31 (26-35)	38 (32-44)***	23.5 (17.9-27.6)
BASFI	23 (19-27)	25 (20-30)	21.2 (14.8-27.6)
BASMI	10 (0;20)	10 (0;20)	10 (0;30)
ASDAS(CRP)	2.0 (1.8-2.3)	2.5 (2.1-2.8)***	1.6 (1.3-1.8)
Swollen joint (%)	9%	11%	9%
hs-CRP (mg/l)	3 (1;7)	5.5 (1.3-9.3)***	2 (0.9;3.9)
PIIANP(ng/ml) 2142 (1742;2658)	2252 (1888;2770)	2459 (1916;2983)#	2171 (1852;2522)
ROC PIIANP (AUC)	0.56 (0.48-0.64)	0.60 (0.50-0.69)	0.52 (0.43-0.62)
C2M(ng/ml) 0.36 (0.30;0.43)	0.41 (0.34;0.50)##	0.44 (0.35;0.50)###	0.39 (0.31-0.5)
ROC C2M (AUC)	0.62 (0.54-0.69)	0.67 (0.58-0.76)	0.56 (0.46-0.66)

#Denotes SpA vs. controls *Denotes TNFi- vs. TNFi+

Conclusion

These findings indicate that active SpA is associated with enhanced cartilage turnover as reflected by increased collagen II degradation and repair. Conversely, this sero-marker profile was normal during TNFi treatment. In addition, C2M discriminates well between healthy subjects and SpA.

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