A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.
Adult ; Arthritis, Rheumatoid ; diagnosis ; metabolism ; Female ; HLA-B27 Antigen ; metabolism ; HLA-DR4 Antigen ; metabolism ; Humans ; Spondylitis, Ankylosing ; diagnosis ; metabolism

IL-32 acts as a pro-inflammatory cytokine by inducing the synthesis of inflammatory molecules as well as promoting the morphological changes involved in the transformation of monocytes into osteoclasts (OCs). Evaluation of the functions of IL-32 has mainly focused on its inflammatory properties, such as involvement in the pathogenesis of various autoimmune diseases. Recently, IL-32 was shown to be involved in bone metabolism, in which it promotes the differentiation and activation of OCs and plays a key role in bone resorption in inflammatory conditions. IL-32γ also regulates bone formation in conditions such as ankylosing spondylitis and osteoporosis. In this review, we summarize the results of recent studies on the role of IL-32γ in bone metabolism in inflammatory arthritis.
Arthritis* ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Bone Resorption ; Inflammation ; Metabolism* ; Monocytes ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteoporosis ; Spondylitis, Ankylosing

BACKGROUNDOsteoporosis and vertebral factures are well recognized features in patients with ankylosing spondylitis (AS). The aim of this study was to investigate the prevalence and risk factors of osteoporosis and vertebral fractures in patients with AS.

METHODSFifty-nine AS patients and 40 healthy controls were enrolled. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA) at posterior-anterior (PA) lumbar, lateral lumbar and hip regions. Thoracic and lumbar X-rays were obtained for morphometric measurements. Clinical, biological and radiological statuses were evaluated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiology Index-total (BASRI-t), erythrocyte sedimentation rate (ESR) and the C-reactive protein levels.

RESULTSOsteoporosis was present in 32% of patients and 5% of controls according to lateral vertebral BMD measurements. Fracture was present in 31% of patients. The effect of some clinical and laboratory parameters on BMD status and vertebral fractures was analyzed in the patient group. Osteoporosis in lateral lumbar DEXA was associated with higher BASMI, BASFI, BASRI-t scores and ESR level. Low hip BMD was associated with low BMI and high BASFI and BASRI-t scores. Vertebral fractures were associated with advanced age, longer disease duration, longer duration since diagnosis, higher BASMI and BASRI-t scores, higher ESR level, reduced femoral and lateral lumbar BMD. Logistic regression analysis revealed that only BASRI-t score was significantly associated with low lateral spinal BMD and BMI and BASFI score were independently associated with low hip BMD. The presence of compression fractures was independently associated with BASRI-t score and low lateral lumbar BMD.

CONCLUSIONSOsteoporosis and vertebral fractures in AS seem to be related to the extent of radiological involvement. A low lateral lumbar BMD is an important risk factor for vertebral fractures.

Absorptiometry, Photon ; Adult ; Blood Sedimentation ; Bone Density ; physiology ; C-Reactive Protein ; metabolism ; Female ; Humans ; Male ; Osteoporosis ; epidemiology ; metabolism ; Spinal Fractures ; epidemiology ; metabolism ; Spondylitis, Ankylosing ; epidemiology ; metabolism ; physiopathology

Chemokine-like factor 1 (CKLF1) is a newly cloned chemotactic cytokine with CCR4 being its functional receptor. Recent evidence demonstrates a role of CKLF1 in arthritis. The aim of this study was to quantify the expression of CKLF1 as well as assess the correlation between CKLF1 and plasma acute-phase markers. Synovium was obtained from 16 osteoarthritis (OA), 15 rheumatoid arthritis (RA) and 10 ankylosing spondylitis (AS) patients undergoing total joint arthroplasty, with other 11 patients treated for meniscal tears during sport accidents serving as normal controls. Levels of CKLF1 and CCR4 mRNA were detected by qRT-PCR, and the expression of CKLF1 was investigated by immunohistochemistry staining, subsequently analyzed with semiquantitative scores. Plasma acute-phase markers of inflammation were determined by ELISA. CKLF1 was found with a particularly up-regulated expression in synovim from AS and RA patients, and CCR4 mRNA levels increased in RA patients, not in OA or AS patients. Elevated levels of plasma markers of inflammation including CRP, ESR and D-dimer were observed in RA. Further, significantly positive correlations between relative expression levels of CKLF1 and CRP/ESR in RA patients and a positive correlation between CKLF1 and ESR in AS patients were found. There was no detectable correlation between CKLF1 and plasma D-dimer. This study confirms an increased but different level of CKLF1 in RA, OA and AS patients, all significantly higher than that in controls. Additionally, the significant positive correlations between CKLF1 levels and CRP/ESR in RA and between CKLF1 and ESR suggest that CKLF1 might contribute to the inflammation state and clinical symptoms in these rheumatic diseases. Further studies are required to investigate the utility of targeting specific CKLF1 for symptom control or disease modification in RA and AS.
Adult ; Arthritis, Rheumatoid ; metabolism ; Biomarkers ; metabolism ; Case-Control Studies ; Chemokines ; genetics ; metabolism ; Female ; Humans ; MARVEL Domain-Containing Proteins ; genetics ; metabolism ; Male ; Middle Aged ; Osteoarthritis ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Receptors, CCR4 ; genetics ; metabolism ; Spondylitis, Ankylosing ; metabolism ; Synovial Fluid ; metabolism

STUDY DESIGN: Preliminary experimental study using a rabbit spondylitis model. PURPOSE: To observe the ossification in a micro-environment containing live Mycobacterium tuberculosis transplanted with bone marrow stromal cells (BMSCs) in rabbits. OVERVIEW OF LITERATURE: BMSCs differentiate to osteoblasts and then osteocytes during ossification. Mycobacterium tuberculosis does not affect BMSC growth in vitro. METHODS: Six rabbits were divided into two groups of three rabbits. One group was positive for spondylitis tuberculosis by culture, polymerase chain reaction (PCR), and histopathologically. The other group was positive by PCR and histopathologically. Both groups were treated using BMSC transplantation and anti-tuberculosis drugs. After 6 weeks, ossification was evaluated by enumerating the number of osteoblasts, osteocytes, and lesion level of calcium. RESULTS: Mean number of osteoblasts was 207.00+/-31.00 in the first group and 220.33+/-73.46 in the second group. Mean number of intra-lesions osteocytes was in the first and second group was 18.33+/-30.04 and 31.00+/-26.87, respectively. Mean calcium level in the first group and second group was 2.94%+/-0.89% and 2.51%+/-0.13%, respectively. Total ossification score in the first and second group was 31.00 and 25.67, respectively. CONCLUSIONS: Mycobacterium tuberculosis provides support for new bone formation by stimulating intra-lesion calcium metabolism. The microscopic environment containing live Mycobacterium tuberculosis enhances ossification.
Bone Marrow* ; Calcium ; Mesenchymal Stromal Cells* ; Metabolism ; Mycobacterium tuberculosis ; Osteoblasts ; Osteocytes ; Osteogenesis* ; Polymerase Chain Reaction ; Rabbits ; Spondylitis ; Tuberculosis

OBJECTIVETo evaluate the clinical efficacy and safety of Qiangji Recipe (QR) in ad- junctive treatment of axial undifferentiated spondyloarthritis (axuSpA) through a four-week open study.

METHODSFifty-four axuSpA patients of Shen-deficiency Du-channel cold syndrome (SDDCS) in line with inclusive criteria were recruited and assigned to the treatment group and the control group according to random digit table, 27 in each group. Patients in the control group took Celecoxib Capsule (0.2 g each time, twice per day). Patients in the treatment group additionally took QR (consisting of Herba Epimedii 15 g, antler glue 15 g, Cibotium Barometz 15 g, eucommia bark 20 g, dipsacus asper 10 g, two toothed achyranthes root 15 g, drynaria 15 g, Taxillus Chinensis 20 g, ground beetle 10 g, scorpion 5 g, wild celery 10 g, notopterygium incisium 10 g, cow-fat seed 10 g, white mustard seed 6 g, and licorice root 6 g, one dose per day, twice daily). The therapeutic course for all was 4 weeks. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), total body pain and spinal pain, patient and physician global assessment on a four-point scale, the Ankylosing Spondylitis Quality of Life (ASQoL), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured before and after 4 weeks of treatment. The primary end point in this study was the proportion of patients with a 20%improvement response accord- ing to the ASAS International Working Group Criteria (ASAS 20 responders) at week 4.

RESULTSTotally 50 patients completed this trial, 26 in the treatment group and 24 in the control group. Improvement of BASDAI, BASFI, BASMI, ASQoL, ESR, and CRP was shown in both groups after treatment. Better effect was shown in the treatment group in all indices except ESR and BASMI after treatment (P < 0.05, P < 0.01). Twenty cases (accounting for 76.92%) in the treatment group achieved ASAS 20 response at week 4, while 12 cases (accounting for 50.00%) in the control group achieved ASAS 20 response at week 4 (P < 0.05). No obvious adverse reaction occurred in the two groups.

CONCLUSIONQR combined Celecoxib Capsule showed better effect in treating axuSpA patients than using Celecoxib Capsule alone.

Blood Sedimentation ; C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Pain ; Quality of Life ; Spondylitis, Ankylosing ; drug therapy

Scleredema is a rare cutaneous mucinosis characterized by chronic diffuse induration of the skin, and it is occasionally associated with a monoclonal gammopathy (MG). Ankylosing spondylitis (AS) is noted to be another, chronic systemic inflammatory disorder of the axial skeleton that may accompany the MG. However, patients with scleredema and AS accompanied with a MG have not been reported in the literature. We here report a 40-yr-old man with scleredema and advanced AS accompanied with a MG of IgA-kappa protein. Widespread, long-standing scleredema has been developed over 10 yrs after the initial manifestation of AS. It is uncertain whether the coexistence of scleredema and AS is more than coincidental.
Adult ; Collagen/metabolism ; Human ; Immunoglobulins, kappa-Chain/chemistry ; Inflammation ; Lumbar Vertebrae/radiography ; Male ; Mucins/metabolism ; Paraproteinemias/*complications/diagnosis ; Scleredema Adultorum/*complications/diagnosis ; Skin/pathology ; Spondylitis, Ankylosing/*complications/diagnosis

Humans ; Immunoglobulin G ; metabolism ; Materia Medica ; Medicine, Chinese Traditional ; Receptors, Tumor Necrosis Factor ; metabolism ; Spondylitis, Ankylosing ; therapy ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the pathological expression and significance of VEGF in patients with active ankylosing spondylitis.

METHODSThe expression of VEGF in the synovial tissues of cacroiliac joint of patients with active AS was detected by using in situ hybridization and the results were compared with those in the patients with pelvic fracture using image analysis system.

RESULTSThe positive expressions of VEGF in the synovial tissues of cacroiliac joint of patients with active AS were stronger than those in the control group (P<0.01).

CONCLUSIONVEGF are important factors in patients with active AS. They are tightly correlated with the process of osteoclasia and pathological new bone formation in the cacroiliac joint of patients with active AS. If we can reduce the expressions of VEGF in the patients with active AS, the process of osteoclasia and pathological new bone formation will be interrupted and this provides a new strategy for the treatment of ankylosing spondylitis.

Adult ; Case-Control Studies ; Female ; Gene Expression Regulation ; Humans ; Male ; RNA, Messenger ; genetics ; metabolism ; Spondylitis, Ankylosing ; genetics ; Synovial Fluid ; cytology ; metabolism ; Vascular Endothelial Growth Factor A ; genetics

OBJECTIVE: To investigate the changes in autophagy of mesenchymal stem cells (MSCs) from patients with ankylosing spondylitis and explore the mechanism for decreased autophagy in ASMSCs. METHODS: MSCs collected from 14 patients with AS (ASMSCs) and from 15 healthy donors (HDMSCs) were cultured in the absence or presence of 25 ng/mL TNF-α for 6 h. Autophagy of the cells was determined by immunofluorescence staining of GFP-LC3B, and the results were confirmed by detecting the protein expressions of autophagy markers LC3 II/LC3 I and P62. The mRNA expressions of the related genes were detected using qRT-PCR, and the protein expressions of the autophagy markers and signaling pathway-related molecules were determined with Western blotting. TG100713 was used to block the PI3K/AKT/mTOR signal pathway, and its effect on autophagy of ASMSCs was evaluated. RESULTS: ASMSCs showed significantly weaker GFP-LC3B puncta staining and lower protein expression levels of LC3 II/LC3 I but higher levels of P62 protein (P < 0.05), indicating a decreased autophagy capacity as compared with HDMSCs. TNF-α-induced ASMSCs showed significantly higher protein expressions of p-PI3K/ PI3K, p-AKT/AKT and p-mTOR/mTOR than HDMSCs (P < 0.05), suggesting hyperactivation of the PI3K/AKT/mTOR signaling pathway in ASMSCs. Blocking PI3K/AKT/mTOR signaling with TG100713 eliminated the difference in TNF-α-induced autophagy between HDMSCs and ASMSCs. CONCLUSION In patients with AS, hyperactivation of the PI3K/AKT/mTOR signaling pathway results in decreased autophagy of the MSCs and potentially contributes to chronic inflammation.
Autophagy ; Humans ; Mesenchymal Stem Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Spondylitis, Ankylosing ; TOR Serine-Threonine Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*