TY - JOUR
T1 - Increased galectin-3 may serve as a serologic signature of pre-rheumatoid arthritis while markers of synovitis and cartilage do not differ between early undifferentiated arthritis subsets
AU - Issa, Saida Farah
AU - Duer-Jensen, Anne
AU - Østergaard, Mikkel
AU - Hørslev-Petersen, Kim
AU - Hetland, Merete L.
AU - Hansen, Michael Sejer
AU - Junker, Kirsten
AU - Lindegaard, Hanne M.
AU - Møller, Jakob M
AU - Junker, Peter
PY - 2017/4/26
Y1 - 2017/4/26
N2 - Background: Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. Methods: One hundred and eleven UA patients were followed-up for at least 12months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets. Results: Galectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6μg/l, interquartile range (IQR) 3.8-5.5) versus non-RA (4.0μg/l, IQR 3.1-4.9; p=0.03) and controls (3.8μg/l, IQR 3.0-4.8; p=0.009). PIIANP was equally depressed in either subset (p<0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53-0.76) while AUC for galectin-3+anti-CCP increased to 0.71 (95% CI 0.59-0.83). Conclusions: Galectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA. Trial registration: KF 11 315829. Registered 25 July 2006.
AB - Background: Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. Methods: One hundred and eleven UA patients were followed-up for at least 12months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets. Results: Galectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6μg/l, interquartile range (IQR) 3.8-5.5) versus non-RA (4.0μg/l, IQR 3.1-4.9; p=0.03) and controls (3.8μg/l, IQR 3.0-4.8; p=0.009). PIIANP was equally depressed in either subset (p<0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53-0.76) while AUC for galectin-3+anti-CCP increased to 0.71 (95% CI 0.59-0.83). Conclusions: Galectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA. Trial registration: KF 11 315829. Registered 25 July 2006.
KW - Cartilage degradation
KW - Collagen II
KW - Galectin-3
KW - Hyaluronan
KW - Undifferentiated arthritis
KW - Cartilage/diagnostic imaging
KW - Galectin 3/blood
KW - Prospective Studies
KW - Follow-Up Studies
KW - Synovitis/blood
KW - Humans
KW - Middle Aged
KW - Male
KW - Young Adult
KW - Adult
KW - Biomarkers/blood
KW - Female
KW - Aged
KW - Arthritis, Rheumatoid/blood
U2 - 10.1186/s13075-017-1282-4
DO - 10.1186/s13075-017-1282-4
M3 - Journal article
C2 - 28446218
AN - SCOPUS:85018355773
SN - 1478-6362
VL - 19
JO - Arthritis Research & Therapy
JF - Arthritis Research & Therapy
M1 - 80
ER -