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ID PMID Title PublicationDate abstract
12180723 Amelioration of accelerated collagen induced arthritis by a novel calcineurin inhibitor, I 2002 Aug OBJECTIVE: To examine the efficacy and toxicity of ISA(TX)247, a novel calcineurin inhibitor, in comparison to cyclosporine (cyclosporin A, CSA) and placebo in established collagen induced arthritis. ISA(TX)247 has up to 3-fold greater potency than CSA in an in vitro whole blood calcineurin inhibition assay and in in vivo solid organ and cell transplantation models. Phase I clinical trials show no discernible nephrotoxicity. METHODS: Type II collagen immunized DBA/Lac J mice with established arthritis were randomized to treatment with ISA(TX)247 (125/250/500 microg/mouse), CSA (250/500 microg/mouse), or drug vehicle, by daily intraperitoneal injection for 10 days from the onset of clinical arthritis. RESULTS: A significant dose dependent reduction in clinical severity was observed in ISA(TX)247 treated but not in CSA treated animals 10 days after the onset of established arthritis, and when examined by area under the curve analysis during the treatment period. Significant improvement in paw swelling (p < 0.001), synovial histology (p < 0.001), and articular cartilage damage scores (p = 0.002) was also noted in ISA(TX)247 treated animals, even in the 125 pg dose group (p = 0.03 for paw swelling and synovial histology). By comparison, CSA had no significant effect on either synovial inflammation or articular cartilage damage. ISA(TX)247 (500 microg dose group) was the only treatment to significantly decrease the development of proximal interphalangeal joint erosions (p < 0.05). A significant reduction in Type II collagen antibody titer was noted in ISA(TX)247 animals in both 250 microg (p = 0.02) and 500 microg (p = 0.004) dosage groups, but only in the 500 microg group for CSA (p = 0.004). Treatment was well tolerated, with no significant toxicity in ISA(TX)247 groups. CONCLUSION: ISA(TX)247 demonstrates efficacy and safety in the treatment of established collagen induced arthritis. Together with its improved potency and nephrotoxicity profile in comparison to CSA, this agent warrants further clinical investigation in autoimmune disease. Phase II studies in rheumatoid arthritis have been initiated.
24387719 Occipitocervicothoracic fixation using a hook and rod system for patients with rheumatoid 2004 Dec Abstract We retrospectively examined the outcomes of occipitocervicothoracic fixation using a hook and rod system for rheumatoid patients with cervical myelopathy in which decompression of the spinal cord and spinal fusion were performed simultaneously at multiple levels. There were 10 female patients with rheumatoid arthritis (ages 51-77 years, average 62.8 years; follow-up period 6 months to 3 years and 9 months, average 2 years and 8 months). Atlantoaxial subluxation was found in 5 patients, vertical subluxation in 4 patients, and subaxial subluxation in 8 patients. The progression of the disorder was assessed as class 4 stage 4 in 3 patients and class 3 stage 4 in 7 patients. The average time taken for surgery was 4 h 41 min, and the average volume of blood loss was 729 ml. There were no complications during surgery. One patient died of malignant lymphoma 1 month after surgery, and one patient died of heart failure 2 years and 3 months after surgery. The average Japanese Orthopaedic Association (JOA) score improved from 7.0 preoperatively to 9.5 postoperatively. Preoperative nuchal pain in 3 patients and difficulty in breathing on flexion of the cervical spine in 2 patients were improved after surgery. Good bony union was obtained in 9 patients. The exception being one patient who died of a disease unrelated to the surgery 1 month postoperatively. Occipitocervicothoracic fixation using a hook and rod system is an easy and safe procedure, and can facilitate not only good bony union, but also adequate decompression of the spinal cord with simultaneous laminoplasty because of the secure long fixation extending to the upper thoracic level and bilateral grafting of a considerable volume of bone.
14513120 [Semeiology of "early arthritis"]. 2003 The main problems related to "early arthritis" are making an accurate diagnosis and predicting the outcome. Clinical evidence strongly suggest that structural damage occur early and that early DMARD treatment improves the long term outcome of disease. Clinical criteria would facilitate early referral of the patients to establish the risk of persistent disease. From the "early arthritis clinics" (E.A.C.) experience has been developed a set of diagnostic criteria characterized by an excellent ability to discriminate, at the first visit, between self-limiting, persistent non-erosive and persistent erosive arthritis. The proposed set consists of 7 criteria: symptom duration (6 weeks - 6 months), morning stiffness of at least 1 hour, arthritis in >/= 3 joints, bilateral compression pain in the metatarsophalangeal joints, IgM-rheumatoid factor positivity, anti-cyclic-citrullinated-peptide antibody positivity and erosions on radiographs of the hands or feet. This approach requests an easy organization to simplify the access to sanitary services and represents an hard challenge both for rheumatologist and health administration.
11966757 The in vivo effects of tumour necrosis factor blockade on the early cell mediated immune e 2002 Mar Anti-TNF therapy is effective in rheumatoid arthritis (RA); however, its mechanisms of action are incompletely understood. T cell-driven mechanisms are thought to play an important role in RA and the effects of TNF blockade on these mechanisms are unclear. Adjuvant arthritis (AA) is a T cell dependent model of inflammatory arthritis. The aims of this study were to investigate the effects of TNF blockade on in vivo T cell cytokine expression and to clarify the role of TNF in the inguinal lymph nodes (ILN) in early arthritis. AA was induced in male DA rats. Rats received either 3 mg/kg or 10 mg/kg PEG sTNF-RI at days 0, 2 and 4 postinduction or 10 mg/kg anti-TNF antibody on day of arthritis induction. Control rats received either saline or normal sheep serum. Paw volume was assessed every 3-4 days. Rats were sacrificed on days 0, 6, 13 and 21 postinduction. Ankles were removed for quantitative radiology and histology. Synovium and ILN were removed for cell culture and to determine mRNA expression of cytokines using semiquantitative RT-PCR. TNF and IFN-gamma protein production was measured using a bioassay and an ELISA. TNF blockade did not suppress mRNA expression of T cell cytokines in the ILN of rats in the early phase of AA, suggesting ongoing T cell activity. TNF protein production by ILN cells in culture was reduced in PEG sTNF-RI treated rats, although mRNA expression was increased in the ILN prior to culture. Early administration of PEG sTNF-RI did not attenuate AA, in contrast to an anti-TNF antibody, which suppressed disease. A shorter half-life for the PEG sTNF-RI compared with the anti-TNF antibody or the development of anti-PEG sTNF-RI antibodies may account for these results.
12508398 Sporadic enteric reactive arthritis and undifferentiated spondyloarthropathy: evidence for 2003 Jan OBJECTIVE: To define the candidate bacterial trigger and cytokine profile of synovial fluid mononuclear cells (SFMC) in patients with sporadic enteric reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA). METHODS: The study group comprised 10 patients with ReA and 23 with uSpA who fulfilled European Spondylarthropathy Study Group criteria. Ten patients with rheumatoid arthritis (RA) served as disease controls. IgG, IgA, and IgM antibodies to Shigella flexneri, Salmonella typhimurium, and Yersinia enterocolitica were measured in sera and SF by ELISA. Peripheral blood mononuclear cell (PBMC) and SFMC proliferation assays were done in the presence or absence of crude bacterial lysates. Bacterial antigens and DNA in synovial cells were detected by indirect immunofluorescence and polymerase chain reaction, respectively. Interferon-g (IFN-g), interleukin 10 (IL-10), and IL-4 were measured in 18 h SFMC culture supernatants in presence of bacterial lysate. RESULTS: Antibodies to S. typhimurium were significantly elevated in the sera of 8 of 25 patients compared to controls (0/22; p < 0.05). The ratio of SF:serum anti-salmonella IgA was significantly higher in patients compared to controls (p < 0.0002). The ratio of SF:serum IgA antibodies to S. typhimurium was higher than that for S. flexneri (p < 0.007) and Y. enterocolitica (p < 0.05). Out of 25 patients, 8, 2, and none had elevated antigen-specific SFMC proliferation response to S. typhimurium, S. flexneri, and Y. enterocolitica, respectively, whereas no control had elevated response. Salmonella antigens were detected in the synovial cells of 4 out of 14 patients. There was significantly higher IFN-g production from SFMC of patients who had increased proliferative response to Salmonella (LTT+) in the presence of Salmonella antigens compared to antigen control. The mean +/- SD of the ratio of IFN-g:IL-10 in the LTT+ patients was significantly lower compared to controls. Conclusion. S. typhimurium is probably one of the triggers for enteric ReA and uSpA in our cohort of patients, and the immune response is characterized by increased production of both IL-10 and IFN-g.
11824946 Gelatinase expression and activity in the synovium and skin of patients with erosive psori 2002 Jan OBJECTIVE: Matrix metalloproteinases (MMP), especially the gelatinases (MMP2, MMP9), have been implicated in several features of inflammatory arthritis including angiogenesis and bone erosions. We examined the expression and activity of the gelatinases and their regulators in psoriatic skin and synovium using tissue immunohistochemistry and a sensitive tissue based zymographic technique. METHODS: Lesional and perilesional skin biopsies and synovial samples obtained by closed needle biopsy from 15 patients with erosive psoriatic arthritis (PsA) were analyzed by immunohistochemistry for the expression of the gelatinases and their regulators, tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, TIMP-2) and membrane type metalloproteinases (MTI-MMP. MT2-MMP), using immunohistochemistry. Synovial tissue from 8 patients with erosive rheumatoid arthritis (RA) was used as a comparison. MMP tissue expression was quantified by 2 blinded independent observers. Immunohistochemical data are reported as the mean percentage positive cells per total nucleated cells in 10 high power fields +/- SD. Functional activity of the gelatinases was measured using a sensitive tissue based zymography technique and corrected for protein content. Zymography data are presented as ng/mg +/- SE. RESULTS: MMP expression was greater in the synovial lining layer (LL) than in the synovial sublining layer (SL) in both PsA and RA tissue for most MMP except collagenase I (MMPI), which was equally distributed between the LL and SL. Expression of MMP or their regulators did not differ between PsA synovial membrane (SM) and RA SM in LL. Moreover, although latent gelatinase A (MMP2) staining in PsA SM was equivalent to RA SM, increased gelatinase A activity was found in PsA SM over RA SM using zymography L82.4 (SD 62.8) vs 10.1 (SD 1.7); p = 0.02]. Compared to PsA SM, lesional skin had lower levels of MT1-MMP (MMP14) (1.4 +/- 1.7 vs 15.7 +/- 8.4; p = 0.009) and MT2-MMP (MMP15) (12.1 +/- 8.7 vs 21.6 +/- 9.9; p = 0.001). CONCLUSION: We characterized the expression and activity of gelatinases in PsA and demonstrate that gelatinase activity in SM of PsA patients with erosive disease is comparable to if not greater than that in RA synovium.
15295000 Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tis 2004 Aug 15 Dendritic cells (DCs) are thought to play a key role in driving the immunopathogenic response underlying chronic inflammatory arthritis. In this study, we have examined the presence and phenotype of plasmacytoid DCs (pDCs) in the synovial fluids (SF) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PA), and osteoarthritis (OA) and determined the chemotactic properties of SF from these patients toward pDCs. Flow cytometry analysis showed that the percentage of pDCs, identified as a population of Lin(-)CD123(++) cells, is 4- to 5-fold higher in RA SF and PA SF than in OA SF. The morphological and immunophenotypic characterization of pDCs isolated from PA and RA SF indicates that they are in an immature state, most likely due to inhibitory factors present in RA SF, but are still able to undergo maturation when exposed ex vivo to viral agent or unmethylated DNA. CD123(+) and BDCA2(+) pDCs were detected by immunohistochemistry in RA synovial tissue in which expression of the IFN-alpha-inducible protein MxA was also found, suggesting production of type I IFN by maturing pDCs. We also show that CXCR3 and CXCR4 are expressed by both blood-derived pDCs and pDCs isolated from RA and PA SF and that CXCL-10, CXCL-11, and CXCL-12 present in RA and PA SF stimulate chemotaxis of blood-derived pDCs. Altogether, these findings suggest that chemokine-driven recruitment of pDCs from the blood to the inflamed synovium could be important in the regulation of the immune response in chronic inflammatory arthritis.
15112095 [Evidence-based use of methotrexate in children with rheumatic disorders. Consensus statem 2004 Apr Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with nonsteroidal antiinflammatory drugs (NSAR) and physiotherapy. Still, in a significant number of cases the disease is resistant to this therapy and treatment with "second line" disease modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as "first choice second line agent" for the treatment of JIA. However, there are considerable differences among pediatric rheumatologists on how and when to use MTX. To increase drug safety, the Working Group for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and the Working Group Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words "Methotrexate" and "juvenile arthritis" limited to age 0-18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin), experience with MTX in adults with rheumatoid arthritis (RA) and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.
12800464 Etoricoxib in the treatment of chronic pain. 2003 May For the many patients who suffer chronic pain, we seek the most effective anti-inflammatory drug with the least side-effect profile and the greatest long-term safety. Etoricoxib, a selective COX2 inhibitor, has been shown to be as effective as non-selective non-steroidal anti-inflammatory drugs in the management of chronic pain in rheumatoid arthritis and osteoarthritis, for periods of up to one year. Data on etoricoxib efficacy in chronic low back pain is beginning to emerge. The side-effect profile of etoricoxib suggests it is well tolerated with similar adverse effects to non-selective NSAIDs. Larger studies are awaited, to see whether superior gastrointestinal tolerability can be proven. Further work will be required to show that etoricoxib is safe in patients with pre-existing cardiovascular or gastrointestinal comorbidity, and the potentially confounding role of aspirin still needs to be elucidated. However, etoricoxib shows promise as a new and effective COX2 inhibitor in clinical practice.
12202127 Chondrocyte apoptosis following intraarticular fracture in humans. 2002 Sep OBJECTIVE: The primary objective of the present study was to establish the degree to which chondrocyte apoptosis occurs in vivo following intraarticular fractures in humans. DESIGN: Fracture cartilage specimens were obtained from patients undergoing surgical intervention for fractures of the articular surface of the proximal tibia. Normal proximal tibia cartilage specimens served as controls. Apoptotic chondrocytes were identified and quantified using TUNEL analysis. RESULTS: The percentage of TUNEL positive chondrocytes in the fractured articular cartilage specimens (mean 18.5%, range 1-44%) was found to be an order of magnitude higher than the percentage observed in control specimens (mean 1.9%, range 0-4%). CONCLUSIONS: The percentage of TUNEL positive chondrocytes following intraarticular fracture is much higher than that reported for chronic degenerative conditions such as osteoarthritis and rheumatoid arthritis. These data provide strong evidence that chondrocyte apoptosis is a consequence of intraarticular fracture and suggest that chondrocyte apoptosis may play a particularly significant role in the subsequent development of post-traumatic arthritis.
11892756 The association of hearing impairment and chronic diseases with psychosocial health status 2002 Feb OBJECTIVES: This study examines the association of hearing impairment and chronic diseases (diabetes mellitus, lung disease, cardiac disease, stroke, cancer, peripheral artery disease, osteoarthritis, rheumatoid arthritis) with psychosocial status (depression, self-efficacy, mastery, loneliness, social network size) in older persons. METHODS: The sample consists of 3,107 persons (55 to 85 years) participating in the Longitudinal Aging Study Amsterdam. MANOVA, adjusted for covariates, was used to test the effect of hearing impairment on the combined outcomes. The association of hearing impairment and chronic diseases with psychosocial status was studied using multivariate regression analyses. RESULTS: Hearing impaired elderly report significantly more depressive symptoms, lower self-efficacy and mastery, more feelings of loneliness, and a smaller social network than normally hearing peers. Whereas chronic diseases show significant associations with some outcomes, hearing impairment is significantly associated with all psychosocial variables. DISCUSSION: The findings emphasize the negative effect of hearing impairment on quality of life.
14985064 Nuclear factor kappaB: a potential therapeutic target in atherosclerosis and thrombosis. 2004 Mar 1 Cardiovascular diseases are the leading cause of morbidity and mortality in Western countries. Atherosclerosis, the background for many cardiovascular diseases, is characterized by the accumulation of lipid and fibrotic entities in large arteries and bears many similarities with chronic inflammatory diseases such as rheumatoid arthritis. Common features include extravasation of blood-derived leukocytes, as well as production of cytokines, chemokines and matrix-degrading enzymes. There are also many shared signaling pathways, including activation of the nuclear factor kappaB (NFkappaB) cascade. In the context of atherosclerosis, there are a range of candidate stimuli which can activate NFkappaB, including traditional risk factors, infectious agents, cytokines and cell-cell contact. Many inflammatory genes relevant to the pathogenesis of atherosclerosis are regulated by NFkappaB, the activated form of which is present in atherosclerotic plaques. Thus, it is essential to understand the role of this important signaling cascade in atherosclerosis, in a quest for more specific therapeutic targets.
12137441 Clinical and biochemical outcome of renal amyloidosis. 2002 Jun AA amyloidosis is a relatively rare disease which complicates chronic inflammatory diseases, chronic infections, familial Mediterranean fever (FMF) and malignant diseases. Although amyloid deposition may be found in many organs, renal involvement dominates the clinical picture. We reviewed 63 patients with AA amyloidosis who presented to our nephrology department between 1995 and 2000. Prognostic markers, detailed history, physical examination and laboratory tests were evaluated. The causes of AA amyloidosis were as follows: FMF 42 (66.6%), pulmonary tuberculosis 9 (14.2%), chronic osteomyelitis 4 (6.3%), bronchiectasia 4 (6.3%), rheumatoid arthritis 1 (1.5%), juvenile idiopathic arthritis 1 (1.5%), inflammatory abdominal aortic aneurysm 1 (1.5 %), unknown aetiology 1 (1.5%). The diagnosis was made on renal biopsies in 63.4% of the patients, while the remaining 36.6% were diagnosed as a result of rectal biopsies. Sixteen patients died. A low serum albumin, high creatinine and high 24-hour urine albumin excretion were associated with high mortality.
12015995 Monitoring the effects of drug treatment in rat models of disease by serum protein analysi 2002 May 5 In this review we list from literature investigations on rat serum proteins using electrophoretic techniques in connection with drug testing. From our own research work, we provide annotated two-dimensional maps of rat serum proteins under control and experimental conditions. Emphasis is on species-specific components and on the effects of acute and chronic inflammation. We discuss our project of structural proteomics on rat serum as a minimally invasive approach to pharmacological investigation, and we outline a typical experimental plan for drug testing according to the above guidelines. We then report in detail on the results of our trials of anti-inflammatory drugs on adjuvant arthritis, an animal model of disease resembling in many aspects human rheumatoid arthritis. We demonstrate a correlation between biochemical parameters and therapeutic findings and outline the advantages of the chosen methodological approach, which proved also sensitive in revealing "side effects" of the test drugs. In an appendix we describe our experimental protocol when performing two-dimensional electrophoresis of rat serum.
11888989 Severe upper airway obstruction from cricoarytenoiditis as the sole presenting manifestati 2002 Mar Upper airway obstruction due to laryngeal involvement is a known complication of systemic lupus erythematosus (SLE). Laryngeal involvement typically accompanies inflammatory activity involving other sites and varies from mild mucosal inflammation to bilateral vocal cord immobility. Cricoarytenoid arthropathy is a rare cause of severe airway obstruction in patients with SLE and almost always occurs in the presence of other associated symptoms. Furthermore, in contrast to patients with rheumatoid arthritis, in whom chronic involvement of cricoarytenoid joints occurs more commonly and often requires surgical intervention, patients with SLE typically present with acute arthritis of cricoarytenoid joints and respond to corticosteroid therapy alone. We describe a patient with known SLE who presented with severe acute upper airway obstruction as the sole manifestation of active SLE after several years of quiescence. The laryngeal involvement progressed from mucosal inflammation to acute cricoarytenoiditis, despite the administration of high-dose corticosteroid therapy, necessitating emergent intubation and tracheostomy. This case illustrates the importance of considering SLE in the differential diagnosis of patients presenting with acute upper airway obstruction.
15156202 Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bon 2004 Jun Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis and periodontitis. Inflammation-induced bone loss of this sort results from elevated numbers of bone-resorbing osteoclasts. Gene targeting studies have shown that the transcription factor nuclear factor-kappa B (NF-kappa B) has a crucial role in osteoclast differentiation, and blocking NF-kappa B is a potential strategy for preventing inflammatory bone resorption. We tested this approach using a cell-permeable peptide inhibitor of the I kappa B-kinase complex, a crucial component of signal transduction pathways to NF-kappa B. The peptide inhibited RANKL-stimulated NF-kappa B activation and osteoclastogenesis both in vitro and in vivo. In addition, this peptide significantly reduced the severity of collagen-induced arthritis in mice by reducing levels of tumor necrosis factor-alpha and interleukin-1 beta, abrogating joint swelling and reducing destruction of bone and cartilage. Therefore, selective inhibition of NF-kappa B activation offers an effective therapeutic approach for inhibiting chronic inflammatory diseases involving bone resorption.
15225374 Strong inhibition of TNF-alpha production and inhibition of IL-8 and COX-2 mRNA expression 2004 In inflammatory processes, the p38 mitogen-activated protein kinase (MAPK) signal transduction route regulates production and expression of cytokines and other inflammatory mediators. Tumor necrosis factor alpha (TNF-alpha) is a pivotal cytokine in rheumatoid arthritis and its production in macrophages is under control of the p38 MAPK route. Inhibition of the p38 MAPK route may inhibit production not only of TNF-alpha, but also of other inflammatory mediators produced by macrophages, and indirectly of inflammatory mediators by other cells induced by TNF-alpha stimulation. Here we investigate the effects of RWJ 67657, a p38 MAPK inhibitor, on mRNA expression and protein production of TNF-alpha and other inflammatory mediators, in monocyte-derived macrophages. A strong inhibition of TNF-alpha was seen at pharmacologically relevant concentrations of RWJ 67657, but also inhibition of mRNA expression of IL-1beta, IL-8, and cyclooxygenase-2 was shown. Furthermore, it was shown that monocyte-derived macrophages have a high constitutive production of matrix metalloproteinase 9, which is not affected by p38 MAPK inhibition. The results presented here may have important implications for the treatment of rheumatoid arthritis.
11924124 [Affinity sorbents having magnetic properties in the clinical picture and diagnosis of com 2002 Affine magnetic sorbents which have no analogs in the practice of our country have been for the first time developed for the rapid diagnosis of various life-threatening diseases (plague, cholera, anthrax, glanders, meliodosis, tularemia, leptospirosis, dysentery, viral hepatitis A) and for the identification of their causative agents. The efficacy of new magnet-controlling test systems has been repeatedly confirmed by their applications in epidemiological events and emergencies: in the epidemiological surveillance of viral hepatitis A in Stavropol and in the Caucasian Mineralnye Vody towns, Stavropol Territory (1994), in the identification of cholera patients, in the detection of transmission factors, when monitoring during large epidemic out-bursts of cholera in Stavropol (1990), Daghestan (1994), as well as in the microbiological monitoring during military conflicts in the Chechen Republic (1995). The application of the sorbents has shown that their sensitivity is 4-5 times as much as that of conventional serological assays. In addition, biotechnologies for the production of polyacrylamide and composite aluminosilicate affine immunosorbents with magnetic properties have been developed. They have been used as the basis for designing immobilized granulated antigen reagents for the immunodiagnosis, differential diagnosis, evaluation of the time course and severity of a disease, the efficiency of therapy in patients with systemic scleroderma, proliferative arthritis, systemic lupus erythematosus, juvenile rheumatoid arthritis, osteochondrosis.
15146426 Association of killer cell immunoglobulin-like receptors with scleroderma. 2004 May OBJECTIVE: Scleroderma is an autoimmune disorder of unknown etiology. A genetic contribution has been demonstrated, and genes influencing activation of the immune system have been potentially identified as candidate genes in this process. The repertoire of killer cell immunoglobulin-like receptors (KIRs) that are involved in the activation of T cells and natural killer cells is highly variable. Recently, an association of KIR2DS2 with vasculitis in patients with rheumatoid arthritis has been reported. Because scleroderma is characterized by an involvement of the vascular system, we sought to determine whether KIR2DS2 is associated with scleroderma. METHODS: We typed 9 KIR genes in 102 patients with scleroderma and in 100 blood donors, using polymerase chain reaction on genomic DNA. RESULTS: Twelve patients with scleroderma, compared with only 2 blood donors, had KIR phenotypes characterized by the presence of the activating KIR2DS2 and the absence of the corresponding inactivating KIR2DL2 (P = 0.005). CONCLUSION: The genetic combination of KIR2DS2+ and KIR2DL2- is associated with scleroderma.
15599472 Juvenile Reiter's syndrome: a case report. 2004 Dec Reiter's syndrome (RS) is uncommon in children, and the classic triad manifestations of RS usually do not occur simultaneously in children. It is often clinically confused with other childhood illnesses. We report a case of RS in a 7-year-old boy with a family history of ankylosing spondylitis. He had developed intermittent arthralgia of the right knee for about 6 months and occasional bilateral eye pain for several months prior to admission. In the 5 days before admission, he developed multiple oral ulcers, weight loss from 25 to 22 kg and fever. Physical examination showed injected bilateral conjunctivae and the right knee joint with swelling, local warmth, and tenderness over the patellar ligament. Laboratory results revealed positive histocompatibility antigen-B27 (HLA-B27), negative rheumatoid factor (RF) and antinuclear antibody (ANA) and normal urinalysis. RS was diagnosed based on the findings of both arthritis and conjunctivitis. The arthritis was treated with acetaminophen and naproxen. In conclusion, juvenile RS should be considered in children with arthritis and conjunctivitis, positive HLA-B27, negative RF and ANA and a family history of related diseases.