Chronic Synovitis Research Articles

HIF-1-Dependent IL-6 Activation in Articular Chondrocytes Initiating Synovitis in Femoral Head Ischemic Osteonecrosis.

Ischemic osteonecrosis of the femoral head in children is associated with chronic hip synovitis and increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the synovial fluid due to unknown mechanisms. The purpose of this study was to investigate hypoxia-inducible factor-1 (HIF-1) activation as a molecular mechanism linking the induction of ischemic osteonecrosis to IL-6 production and the initiation of hip synovitis. Ischemic osteonecrosis was surgically induced in the right femoral head of 6 piglets. A histologic score, synovial fluid volume, and IL-6 level were used to assess hip synovitis. IL-6 immunostaining of articular cartilage and synovial tissue was performed as well. To study the role of HIF-1 in IL-6 activation, in vitro experiments using an HIF-1α activator (deferoxamine) and inhibitor (HIF-1 small interfering-RNA [siRNA]) were carried out. Synovial cell responses to hypoxic chondrocyte-conditioned media with and without an IL-6 receptor blocker (tocilizumab) were assessed on the basis of IL-1β and tumor necrosis factor-alpha (TNF-α) gene expressions and with a synovial cell-proliferation assay. Induction of ischemic osteonecrosis produced hip synovitis and increased IL-6 levels in the synovial fluid. Immunostaining and protein analysis demonstrated articular chondrocytes as a source of increased IL-6 production. When articular chondrocytes were cultured under hypoxic conditions, significantly increased HIF-1α and IL-6 expressions were observed. Under hypoxic culture conditions, IL-6 gene expression was significantly increased by HIF-1α activation using deferoxamine and inhibited by HIF-1α inhibition using HIF-1 siRNA. Synovial cells exposed to hypoxic chondrocyte-conditioned medium showed significant increases in IL-1β and TNF-α gene expressions and cell proliferation, which were inhibited by the IL-6 receptor blocker tocilizumab. Induction of ischemic osteonecrosis results in IL-6 production in the articular cartilage through an HIF-1-dependent pathway. IL-6 produced by hypoxic articular chondrocytes stimulates inflammatory cytokine responses in synovial cells, which were significantly decreased by tocilizumab. This study provides new insight into the inherent relationship between the induction of ischemia and the initiation of hip synovitis following ischemic osteonecrosis and suggests a potential therapeutic target in the treatment of the synovitis.

Parasitoses intestinais: efeito protetor na artrite reumatoide?

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, with a progressive course, characterized by chronic synovitis that may evolve with deformities and functional disability, and whose early treatment minimizes joint damage. Its etiopathogenesis is not fully elucidated but comprises immunologic responses mediated by T helper cells (Th1). An apparent minor severity of RA in patients from regions with lower income could be associated with a higher prevalence of gut parasites, especially helminths. Strictly, a shift in the immune response towards the predominance of T helper cells (Th2), due to the chronic exposure to helminths, could modulate negatively the inflammation in RA patients, resulting in lower severity/joint injury. The interaction between the immunological responses of parasitic helminths in rheumatoid arthritis patients is the purpose of this paper.

TREATMENT OF ASEPTIC DISEASES OF LIMB DISTAL PART JOINTS IN UZBEK SPORT HORSES

In this study a treatment was prescribed for the horses with the diagnosis of chronic aseptic synovitis and periarticular fibrosis. For all experimental groups (n=3) there was used the traditional method of treatment with only one difference, that for animals of the 1st group additionally auto–blood therapy processed with laser was used. For the animals of the second group there was injection auto–blood intramuscularly 0.5 ml.kg-1 of body mass of an animal and the preparation “Hondralon” in the doze of 2 ml intra-joint which strengthens the regeneration of cartilage tissue. And animals of the 3rd experimental group were treated only with traditional method. On the base of clinical observations, morphological, biochemical and immunological indexes of blood the most effective method of treatment of joint diseases of horse limb distal part was proved- application of parenteral injection of auto-blood and specific preparation “Hondralon” together with traditional methods of treatment and the period of treatment was reduced to 5 days in average.

Differential Diagnosis of Large Joints Chronical Synovitis

To determine the genesis of large joint chronical synovitis the morphologic picture (facia) of synovial exudate was studied in 23 patients using the method of cuneate dehydration of biological liquid. Cytologic investigation showed leukocytosis with prevalence of neutrophils in all patients. All patients were divided into two groups. First group included 8 patients in whom septic pattern of inflammation was confirmed by the results of synovial fluid culture inoculation, second group - 15 patients with negative bacteriologic study results. The obtained data enabled to describe two types of synovial fluid facia that allowed differentiating septic pattern of inflammation from the reactive one.

Differential Diagnosis of Large Joints Chronical Synovitis

To determine the genesis of large joint chronical synovitis the morphologic picture (facia) of synovial exudate was studied in 23 patients using the method of cuneate dehydration of biological liquid. Cytologic investigation showed leukocytosis with prevalence of neutrophils in all patients. All patients were divided into two groups. First group included 8 patients in whom septic pattern of inflammation was confirmed by the results of synovial fluid culture inoculation, second group - 15 patients with negative bacteriologic study results. The obtained data enabled to describe two types of synovial fluid facia that allowed differentiating septic pattern of inflammation from the reactive one.

Gout management: an update

Gout is the most frequent arthritis worldwide. Despite progress in therapeutic options the majority of gout patients are still insufficiently treated. International guidelines (ACR, EULAR, 3e initiative) clearly specify treatment targets: keep the patient flare-free and maintain a low urate serum level (< 360 µmol/l). The treat to target strategy includes therapy of flares, urate lowering treatment (ULT) and prophylaxis of flares. Evolution of gout guidelines over several years shows a broader indication for ULT, mandatory prophylaxis of flares during the initiation of ULT over several months and an earlier start of ULT in patients with flares as soon as symptoms have diminished. Colchicine is the preferred specific flare treatment, Caution has to be taken especially in patients with kidney disease, patients with hepatic dysfunction or in patients with interacting comedication. Low dose oral colchicine is nowadays the standard flare treatment. NSAIDs and prednisone are valuable alternatives. Interleukin-1 blockers offer a quick resolution of flares and may be an option in patients with chronic gout and severe kidney disease. Xanthinoxidase inhibitors (XOI) are the mainstay of ULT, with allopurinol still being the preferred XOI. The recently approved XOI febuxostat is eliminated mostly by the liver and can induce a faster lowering of urate. Uricosuric drugs such as probenecid are recommended in patients with sufficient renal function in whom the treatment goals cannot be reached with XOI. In Switzerland, only the two gout-lowering drugs allopurinol and probenecid are available, which reduces the therapeutic possibilities. Treatment success is often hampered by malcompliance. Recent guidelines stress the importance of patient education to ameliorate compliance. Comorbidities such as metabolic syndrome, cardiovascular and kidney disease are often found in gout patients. Patients with severe kidney disease are the most difficult to treat: the choice of antiinflammatory treatment is narrowed, ULT has to be uptitrated very carefully and patients often suffer from repeated flares. Another factor associated with treatment failure is the low physician’s adherence towards the guidelines. Therapeutic failure can lead to chronic and refractory gout (polyarticular gout, uncontrolled flare activity, chronic synovitis, destructive tophi) which makes the further management very difficult. Most gout patients are treated in primary care settings. Patients with chronic gout or at high risk for development of chronic gout (in particular patients with severe kidney disease or patients transplanted) should be additionally treated by a rheumatologist.

Arthroscopic synovectomy considerably reduces bleeding frequency and improves joint function in hemophilic patients with chronic synovitis

Summary Background/Introduction Hemophilic arthropathy (HA) is the most common complication in patients with hemophilia. Arthroscopic synovectomy in HA is the optimal choice of treatment because it is less invasive. Purpose/Aim To demonstrate the effectiveness of arthroscopic synovectomy for HA involving the knees, elbows, and ankles. Methods This study retrospectively analyzed 11 patients with chronic synovitis with repeated hemoarthrosis (13 joints: 5 knees, 4 elbows, and 4 ankles) between August 2011 and August 2013. The joints that did not respond well to secondary prophylactic factor replacement and physical therapy underwent arthroscopic synovectomy for further treatment. Patient profiles, joint pain scores, bleeding frequency, and joint function scores were reviewed. Results The mean visual analog scale scores for pain decreased from 77.1 mm preoperatively to 27.7 mm postoperatively ( p p p Conclusion Arthroscopic synovectomy, a less invasive procedure for HA, significantly reduced joint pain, prevented bleeding episodes, and improved joint function with few complications.

Radiosynovectomy in haemophilic synovitis of elbows and ankles: Is the effectiveness of yttrium-90 and rhenium-186 different?

BackgroundRadiosynovectomy (RS) reduces the number of haemarthroses and the synovial size in chronic haemophilic synovitis. The purpose of this study was to quantitatively compare the effectiveness of two types of RS (yttrium-90 vs. rhenium-186) in terms of the objective improvement of haemarthroses and synovial size. MethodsSeventy RSs were performed in 70 joints (44 elbows, 26 ankles) of 70 haemophiliacs diagnosed with chronic synovitis. Yttrium-90 was used in 21 joints and rhenium-186 was used in 49 joints. The mean patient age was 20.61years. ResultsRS resulted in significant improvement in the three variables studied (six months before RS vs. six months after RS), namely in the number of episodes of haemarthrosis (67.8% improvement); the size of the synovium as measured by means of a clinical scale (43.8% improvement) and imaging techniques in millimetres (26.7% improvement). We did not find significant statistical differences between yttrium-90 and rhenium-186 regarding their efficacy. No correlation was found between the results and other variables: age, joint (ankle or elbow), presence or absence of radiological involvement, type of haemophilia (A or B), grade of haemophilia (mild, moderate or severe), previous haematological treatment (on demand or prophylaxis), and the presence or absence of inhibitor ConclusionsYttrium-90 RS and rhenium-186 RS were equally effective in reducing the number of haemarthroses and the size of the synovium in ankles and elbows in the short-term (6months). No correlation was found between the results and other patients´ characteristics.

Research progress on risk factors of osteoporotic fractures in patients with rheumatoid arthritis

Rheumatoid arthritis is a autoimmune diseases characterized as joint chronic synovitis, and is accompanied with systemic damage. Osteoporotic fracture is one of the common complications of rheumatoid arthritis, which may decrease quality of life, and even increase the mortality of patients. Variety of factors may be associated with the occurrence of osteoporotic fractures in rheumatoid arthritis patients. In this article, through the literature review we discuss the risk factors of osteoporotic fracture, including vitamin D deficiency, lower limb muscle strength and balance ability in rheumatoid arthritis patients. Key words: Arthritis, rheumatoid; Osteoporotic fracture

Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning.

The molecular mechanism of citrullination involves the calcium-dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes induce a stereochemical modification of normal proteins and transform them into autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint inflammatory events followed by chronic synovitis, pannus formation, and finally, cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce autoantigens, we investigated five possible synovial protein targets of PAD enzymes. We measured PAD2, PAD4, and citrullinated proteins in 10 rheumatoid and 10 osteoarthritis synovial biopsies and then assessed the post-translational modifications of fibrinogen, cytokeratin, tubulin, IgG, and vimentin proteins using a double-fluorescence assay with specific antibodies and an affinity-purified anti-citrullinated peptide (CCP) antibody. The degree of co-localization was analyzed, and statistical significance was determined by ANOVA, Fisher's exact test, and regression analysis. The principal results of this study demonstrated that citrullinated proteins, such as fibrinogen, IgG, and other probed proteins, were targets of PAD2 and PAD4 activity in rheumatoid synovial biopsies, whereas osteoarthritis biopsies were negative for this enzyme (p<0.0001). An analysis of citrullination sites using the UniProtKB/Swiss-Prot data bank predicts that the secondary structure of the analyzed proteins displays most of the sites for citrullination; a discussion regarding its possible meaning in terms of pathogenesis is made. Our results support the conclusion that the synovial citrullination of proteins is PAD2 and PAD4 dependent. Furthermore, there is a collection of candidate proteins that can be citrullinated.

Effects of intraarticular (32)P colloid in the treatment of hemophilic synovitis of the knee: A short term clinical study.

Background:Chronic synovitis is a consequence of recurrent intraarticular hemorrhage in patients with hemophilia. Eventually, synovitis leads to degeneration of the articular cartilage, with serious consequences that impact the quality-of-life in hemophiliacs. The aim of our study was to investigate the short term clinical effects of intraarticular injection of the radionuclide preparation32P colloid (32P-labelled colloidal chromic phosphate suspension) on recurrent intraarticular hemorrhages in patients with hemophilic synovitis of the knee.Materials and Methods:Patients who met the inclusion criteria (n = 22) were enrolled in an open-label study between October 2011 and September 2012.32P colloid was injected into the knee joint and patients were followed up over 6 months after treatment. Hemorrhage frequency, visual analog scale pain score, hospital for special surgery knee score, knee circumference, upper knee circumference, knee diameter, and knee range of motion (ROM) were compared before and after treatment with intraarticular32P colloid injection.Results:In 24 knees evaluated in 22 participating patients, there was a significant reduction in the number of hemorrhages after32P colloid treatment, along with significant pain relief. However, there were no statistically significant changes in the degree of joint swelling, degree of muscle atrophy and knee ROM between the pre and post treatment evaluations.Conclusion:The frequency of joint hemorrhage in patients with hemophilic knee synovitis can be significantly reduced and local symptoms can be improved in the short term by intraarticular injection of32P colloid.

It's not what it looks like: challenges in diagnosis of synovial lesions of the knee joint.

BackgroundWith the advent of MRI (Magnetic Resonance Imaging), Synovial lesions around knee are being more and more easily detected. Synovial lesions of knee present with boggy swelling, effusion, pain, and restriction of motion. Differential diagnoses of such lesions include pigmented villonodular synovitis, synovial lipoma, synovial chondromatosis, rheumatoid arthritis, synovial hemangioma, amyloid arthropathy, xanthomata and lipoma arborescens. CT and MRI often help in diagnosis of such lesions. MRI of Lipoma Arborescens has been regarded to have characteristic diagnostic appearance – it includes a synovial mass with frond-like architecture and fat signal intensity on all pulse sequences. Sometimes Lipoma Arborescens can present in conjunction with inflammatory arthritis. Synovectomy is often curative for such conditions.FindingsWe report two cases where lesions diagnosed as Lipoma Arborescens on MRI subsequently revealed to be chronic inflammatory synovitis, characterized by absence of fat infiltration in histopathological examination – refuting the original diagnosis. There was infiltration of lymphocytes and neutrophils in the synovium, suggestive of chronic inflammatory arthritis. Both of these patients required management from rheumatologist, and had relief of symptoms after use of methotrexate and hydroxychloroquine. We also report a third case, where a loose body appearing as chondral fragment on arthroscopy was subsequently diagnosed as an organized hematoma on histopathological examination.ConclusionDiagnostic pitfalls after MRI of the knee is not uncommon. For example - normal variant of meniscomeniscal ligaments have been reported as meniscal tears; motion artifacts have been falsely reported as meniscal injuries; and meniscofemoral ligament can appear as free osteochondral fragment. In most of these cases, a routine arthroscopy is enough to clear the confusion. However, as evident in the three cases described here - in some synovial lesions of knee joint, even after MRI and arthroscopic examination, histopathological confirmation may still be prudent. In spite of availability of advanced imaging technologies and high definition arthroscopy equipment, an arthroscopy surgeon still must not forget the value of histopathological examination in establishing the true nature of synovial lesions of the knee joint.

Histological Appearance of the Synovial Membrane after Treatment of Knee Osteoarthritis with Polyacrylamide Gel Injections: A Case Report

Knee osteoarthritis (OA) caused by cartilage damage and synovitis is a painful disease, for which the only effective treatment today is total knee replacement. Polyacrylamide hydrogel (PAAG) is a synthetic non-degradable and non-toxic tissue filler, which allows host cell integration with formation of a scaffold of fibrous tissue inside the gel. A histo-pathological pilot study using this gel for intra-articular injection in rabbit and horse joints has shown that it forms an integrated layer within the upper part of the synovial membrane, and clinical studies of horse joints and human knee joints with OA has shown promising long-term results in pain reduction. It has therefore been the hope that this type of treatment could prolong the time leading up to total knee replacement more effectively than today. The current case report from one of the patients included in the clinical study mentioned above describes, for the first time in a human, how biopsies obtained during meniscectomy after 9 months display the same type of synovial augmentation as seen in horse joints with OA, and that the filler effect from the integrated gel persists in spite of areas with chronic synovitis and microscopic fibrosis.

Orthopedic disorders of the knee in hemophilia: A current concept review.

The knee is frequently affected by severe orthopedic changes known as hemophilic arthropathy (HA) in patients with deficiency of coagulation factor VIII or IX and thus this manuscript seeks to present a current perspective of the role of the orthopedic surgeon in the management of these problems. Lifelong factor replacement therapy (FRT) is optimal to prevent HA, however adherence to this regerous treatment is challenging leading to breakthrough bleeding. In patients with chronic hemophilic synovitis, the prelude to HA, radiosynovectomy (RS) is the optimal to ameliorate bleeding. Surgery in people with hemophilia (PWH) is associated with a high risk of bleeding and infection, and must be performed with FRT. A coordinated effort including orthopedic surgeons, hematologists, physical medicine and rehabilitation physicians, physiotherapists and other team members is key to optimal outcomes. Ideally, orthopedic procedures should be performed in specialized hospitals with experienced teams. Until we are able to prevent orthopedic problems of the knee in PWH will have to continue performing orthopedic procedures (arthrocentesis, RS, arthroscopic synovectomy, hamstring release, arthroscopic debridement, alignment osteotomy, and total knee arthroplasty). By using the aforementioned procedures, the quality of life of PWH will be improved.

Radioisotope synoviorthesis in pediatric and adolescent patients with hemophilia

ObjectiveTo assess the outcome and adverse-effects of the radioisotope synoviorthesis in pediatric and adolescent patients with hemophilia. Material and methodsProspective study of historical cohort was conducted. A total of 20 consecutive hemophiliacs with a mean age of 13.1 years (range 4–17) were included with a mean follow-up of 64.9 months (range 18–109). The diagnosis of synovitis was established on the basis of clinical follow-up including radiological images (radiography and/or MRI). For evaluation, the classification proposed by Fernandez-Palazzi was used. Inclusion criteria: Patients aged less than 18 years old with hemophilia and more than one haemarthrosis in less than 3 months remaining a chronic synovitis despite prophylactic therapy intensification. Exclusion criteria: Any contraindication for radionuclide synoviorthesis. Twenty-seven radioisotope synoviorthesis with 90Y-citrate-colloid and/or 186Re-sulphide-colloid were done. The effectiveness of the procedure was assessed through pre and posttreatment clinical comparison at 6 months after radioisotope synoviorthesis. ResultsNineteen of the 27 synoviorthesis (70.3%) had a good or excellent response and 8 joints (29.7%) had partial response. It was necessary to repeat the procedure in 3 joints in 3 different patients, obtaining in all cases a good or excellent response. We appreciated inflammatory reaction after procedure in 4 cases (14.8%), which improved with analgesics and nonsteroidal anti-inflamatory drugs. None of the patients presented malignant or premalignant lesions during the follow-up. ConclusionThe radionuclide synoviorthesis is a very effective procedure in pediatric and adolescent patients with hemophilia, being a minimally invasive procedure, easy to perform, safe and with minimal side effects.

Anti-RANKL antibody for the treatment of bone and cartilage destruction in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by chronic synovitis and RANKL-dependent osteoclastogenesis leading to bone damage, which causes severe physical disability. Focal and systemic bone and cartilage destruction including secondary osteoporosis contributes to the morbidity associated with RA. The biologics targeting TNF and IL-6 has revolutionized the treatment of RA, producing significant improvements in clinical and structural outcomes. Furthermore, an anti-RANKL antibody denosumab possesses a potential to inhibit joint destruction as well as systemic osteoporosis. Targeting RANKL therapy will most likely enlarge the possibilities of osteoporosis treatment and improve the prognosis in RA patients.

Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance.

The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment.

Indications and contraindications for radiosynoviorthesis

Radiosynoviorthesis (RSO) provides a simple method for the treatment of patients with chronic synovitis and has only few side effects. Evidence-based indications and contraindications for performing RSO based on the current literature are presented. Published information on the indications and contraindications for performing RSO in chronic synovitis were analyzed and summarized. According to the guideline recommendations of the German Society of Rheumatology indications for RSO are given in patients with rheumatoid arthritis, seronegative spondyloarthropathy, crystal arthropathy, villonodular synovitis and hemophilia with recurrent joint bleeding. Osteoarthritis with documented reactive synovitis is also regarded as an indication in the guidelines of the nuclear medicine societies. The European League Against Rheumatism (EULAR) and the German Society of Rheumatology (DGRh) have given no recommendations for using RSO in osteoarthritis. Given the correct indications RSO shows high success rates. The effects of RSO with the named secondary side effects last on average for 5 years. Crucial for the success of RSO are the correct indications, the correct timing and combination with other therapeutic procedures, such as surgical synovectomy.

Influence of Matrix metalloproteinase 1 and 3 genetic variations on susceptibility and severity of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease affecting children aged less than 16 years, characterized by chronic synovitis, cartilage damage, and bony erosions mediated by matrix metalloproteinases (MMPs), mainly MMP-1 and MMP-3. The purpose of this study was to investigate MMP-1 and MMP-3 gene polymorphisms in patients with JIA, the role of genes in susceptibility to JIA, and their associations with JIA activity and prognosis. Case-control study included 100 patients diagnosed with JIA, according to the criteria of the International League of Associations for Rheumatology (ILAR), and 100 healthy children, age and sex matched, as controls. The MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of MMP-1 and MMP 3 were measured by enzyme-linked immunosorbent assay. There were significant differences between patients with JIA and control groups regarding the genotype and allele frequencies distributions of both MMP-1 1G/2G and MMP-3 5A/6A polymorphisms. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in patients with JIA than in controls (OD = 2.8, P = 0.002). The prevalence of MMP-1 2G and 6A allele for MMP-3 polymorphism was found to be significantly associated with persistent oligoarticular, rheumatoid factor (RF)-positive polyarthritis, and systemic JIA groups. There were significantly increased serum levels of MMP-1 and MMP-3 associated with 2G/6A haplotype in the patient group, especially with the polyarticular RF (+ve) group than in other groups and the control group. MMP-1 and MMP-3 haplotypes could be useful genetic markers for JIA susceptibility and severity in the juvenile Egyptian population. Moreover, our data further support the use of serum MMP-3 and MMP-1 as specific markers of disease activity in JIA.