Changes of serum levels of MMP-3, sRANKL, and OPG in juvenile-onset ankylosing spondylitis patients carrying different HLA-B27 subtypes.

Ankylosing spondylitis (AS) patients whose symptom onset occurs before 16 years of age are termed juvenile-onset ankylosing spondylitis (JAS). Investigations suggested that JAS had worse functional outcome, and abnormality of bone metabolism can appear in early stage of AS. The objectives of this study are to compare changes of serum inflammatory and bone metabolic markers and to explore the relationship between these biomarkers and disease activity in JAS with different HLA-B27 subtypes. Serum matrix metallopeptidase-3 (MMP-3), soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin (OPG) were detected by ELISA in 56, 62, and 68 JAS patients, respectively, and 32 healthy individuals were as controls. Serum MMP-3 and sRANKL were significantly higher and OPG in JAS was slightly higher than those in controls. There was no significant difference in the level of MMP-3, sRANKL, and OPG among JAS patients with B27 negativity, B*2704, B*2705, and B*2715, respectively. Serum levels of MMP-3 showed positive correlation with BASDAI and BASFI (Bath Ankylosing Spondylitis Disease Activity Index and Functional Index). Serum level of sRANKL showed positive correlation with MMP-3 and negative correlation with disease duration. The significantly higher sRANKL expression suggested the enhanced osteoclast function and imbalance of RANKL/OPG system in the inflammatory process of JAS patients carrying different B27 subtypes. It should be paid attention to the abnormality of bone metabolism during the treatment of JAS.

Value of the peripheral blood B-cells subsets in patients with ankylosing spondylitis.

BACKGROUND: The role of B-cell remains an enigma in the pathogenesis of ankylosing spondylitis (AS). This study aimed to investigate the distributions of B-cells and subsets in peripheral blood of AS patients and observe their changes in etanercept-treated AS patents. METHODS: We detected the proportions of CD19(+) B-cell, naive B-cell (CD19(+)CD27-), memory B-cell (CD19(+)CD27dim) and plasmablast (CD19(+)CD27high) in peripheral blood of 66 patients with AS (39 at active stage, 27 at stable stage; 35 patients with peripheral joint involvement, 31 patients with axial involvement alone), 30 patients with rheumatoid arthritis (RA) and 30 healthy volunteers using flow cytometry. And then we observed the changes of the above indexes of 39 active AS patients treated with etanercept in a randomized, double-blind, placebo-controlled trial. RESULTS: (1) Percentages of CD19(+) B-cells in active or peripheral joint involvement AS patients increased more obviously than those in stable or axial involvement alone AS patients (both P = 0.001), and percentage of CD19(+)CD27high B-cells in AS patients with peripheral joint involvement was significantly higher than that in cases with axial involvement alone or healthy volunteers (P = 0.005 and 0.006, respectively); (2) The percentage of CD19(+) B-cells in AS patients was positively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Patient's Global Assessment (PGA) scores, total back pain scores and nocturnal back pain scores (r = 0.270, 0.255, 0.251 and 0.266, P = 0.029, 0.039, 0.042 and 0.031, respectively); (3) At week 6 and week 12, there were no statistical differences of the percentages of B-cells and subsets between etanercept group and placebo group of AS patients (P > 0.05); the percentage of CD19(+) B-cells in etanercept group was higher than that in healthy volunteers at week 12 (t = 3.320, P = 0.003). CONCLUSIONS: Misbalance is present in B-cells and some subsets in peripheral blood of active AS patients with peripheral joint involved. B-cells might play an important role in the pathogenesis of AS patients. The high percentage of CD19(+) B-cells in active AS patients cannot be down-regulated after 12-week etanercept treatment.

[Screening and verification of questionnaire indexes for epidemiological studies on spondyloarthropathy].

OBJECTIVE: To screen the parameters of questionnaire in prevalence survey of spondyloarthropathy (SpA) in China, and to evaluate the value and feasibility of questionnaire used in prevalence survey. METHODS: A questionnaire study on SpA with 12 questions involved was performed which came from a epidemiological survey on SpA in Brittany, France. RESULTS: (1) We found difference on the sensitivity and specificity of some indexes in the questionnaires between the French study and the one developed by ourselves. The sensitivity differed between the published French paper and ours in the following indexes: onset age, psoriasis and inflammatory bowel disease. The specificity of the indexes would include spinal pain, insidious onset, morning stiffness, duration more than 3 months and radiographic manifestation also showed differences. (2) Excluding the radiographic abnormality, we ran the logistic regression and concluded that the following parameters were the independent indexes which suggesting the existence of the disease: spinal pain onset before 40 years of age, having spinal stiffness in the morning having positive family history and having buttock pain and heel pain. (3) Based on the result of each question of the questionnaire, indices of distinguishing the cases and controls were identified. CONCLUSION: The questionnaire verified in our study was a new, simple, valuable and feasible one for SpA prevalence study and in screening the potential SpA patients.