ABSTRACT
Spondyloarthritis (SpA) is a common rheumatic disorder of the young, marred by delay in diagnosis, and paucity of biomarkers of disease activity. The present study aimed to explore the potential of serum metabolic profiling of patients with SpA to identify biomarker for the diagnosis and assessment of disease activity. The serum metabolic profiles of 81 patients with SpA were compared with that of 86 healthy controls (HCs) using nuclear magnetic resonance (NMR)-based metabolomics approach. Seventeen patients were followed up after 3 months of standard treatment, and paired sera were analyzed for effects of therapy. Comparisons were done using the multivariate partial least squares discriminant analysis (PLS-DA), and the discriminatory metabolic entities were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (p value < 0.05). We found that the serum metabolic profiles differed significantly in SpA as compared with HCs. Compared with HC, the SpA patients were characterized by increased serum levels of amino acids, acetate, choline, N-acetyl glycoproteins, Nα-acetyl lysine, creatine/creatinine, and so forth and decreased levels of low-/very low-density lipoproteins and polyunsaturated lipids. PLS-DA analysis also revealed metabolic differences between axial and peripheral SpA patients. Further metabolite profiles were found to differ with disease activity and treatment in responding patients. The results presented in this study demonstrate the potential of serum metabolic profiling of axial SpA as a useful tool for diagnosis, prediction of peripheral disease, assessment of disease activity, and treatment response.
Subject(s)
Arthritis, Reactive/diagnosis , Biomarkers/blood , Adult , Arthritis, Reactive/blood , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Diagnosis, Differential , Discriminant Analysis , Female , Humans , Least-Squares Analysis , Male , Metabolome , Metabolomics/statistics & numerical data , Middle Aged , Nuclear Magnetic Resonance, Biomolecular , Principal Component Analysis , Young AdultABSTRACT
BACKGROUND The aim of this study was to explore the correlation between HLA-B27 and the intracellular elimination, replication, and trafficking of Salmonella enteritidis (S. enteritidis) collected from patients with reactive arthritis. MATERIAL AND METHODS Confocal microscopy, flow cytometry, and sandwich enzyme-linked immunosorbent assay (ELISA) were employed in this study to evaluate the localization of proteins of interest, to assess the intracellular trafficking of S. enteritidis, and to measure the production of cytokines of interest. RESULTS HLA-B27 was negatively associated with intracellular S. enteritidis elimination in healthy human monocytes/macrophages. In S. enteritidis infected monocytes/macrophages, HLA-27B was also negatively correlated with bacteria elimination but positively related to bacteria replication. S. enteritidis did not co-localize with NRAMP1 and LAMP1/2 in HLA-B27 cells. S. enteritidis did not co-exist with transferrin or dextran within HLA-B27 and A2 cells. CONCLUSIONS HLA-B27 is closely associated with the intracellular elimination and replication of S. enteritidis. Replicated bacteria in HLA-B27 monocytic cells were located within unique vacuoles rather than disturbing host endocytosis.
Subject(s)
Arthritis, Reactive/microbiology , HLA-B27 Antigen/analysis , Adult , Arthritis/microbiology , Arthritis, Reactive/blood , Biomarkers/blood , Cell Line , Cytokines/metabolism , Female , HLA-B27 Antigen/blood , Humans , Macrophages/immunology , Macrophages/microbiology , Male , Middle Aged , Monocytes/immunology , Monocytes/microbiology , Salmonella enteritidis/metabolism , Salmonella enteritidis/pathogenicity , U937 CellsABSTRACT
Reactive arthritis has been classically defined as an aseptic arthritis induced by a bacterial infection in another organ. If the classical form of reactive arthritis is in fact a spondyloarthritis triggered by a urogenital or intestinal bacterial infection, it is not necessarily sterile, and in some cases it may be worthwhile to treat a chronic infection with long-term antibiotherapy. In a broader definition, the concept of reactive arthritis is widened to other post-infectious rheumatism, such as post-streptococcal arthritis or post-viral arthritis.
Subject(s)
Arthritis, Reactive/diagnosis , Arthritis, Reactive/etiology , Bacterial Infections/complications , Virus Diseases/complications , Arthritis, Reactive/blood , Arthritis, Reactive/classification , Arthritis, Reactive/drug therapy , Humans , Serologic Tests , Time FactorsABSTRACT
A 48-year-old male with history of chronic arthritis and uveitis presented with 1 year of progressively reduced exercise capacity and nonexertional chest pain. Physical examination was consistent with severe aortic insufficiency. An electrocardiogram demonstrated sinus rhythm with first degree atrioventricular block. Transthoracic and transesophageal echocardiography demonstrated severe lone central aortic insufficiency of a trileaflet valve due to leaflet thickening, retraction of leaflet margins and mild aortic root dilation in the setting of left ventricular dilatation. In addition, computed tomographic angiography revealed a small focal aneurysm of the distal transverse arch. He was found to be positive for the immunogenetic marker HLA-B27. The patient subsequently underwent uncomplicated mechanical aortic valve replacement. The diagnosis of HLA-B27 associated cardiac disease should be entertained in any individual with lone aortic insufficiency, especially if accompanied by conduction disease.
Subject(s)
Aortic Valve Insufficiency/complications , Aortic Valve Insufficiency/diagnostic imaging , Arthritis, Reactive/complications , Arthritis, Reactive/diagnosis , Atrioventricular Block/complications , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Insufficiency/surgery , Arthritis, Reactive/blood , Atrioventricular Block/diagnosis , Biomarkers/blood , Echocardiography, Transesophageal/methods , Electrocardiography/methods , HLA-B27 Antigen/blood , Heart Valve Prosthesis , Humans , Male , Middle AgedABSTRACT
INTRODUCTION: Campylobacterjejuni is has been found to be the leading cause of bacterial gastroenteritis worldwide. Clinical manifestation on enterocolitis caused by C. jejuni are diarrhea, fever, abdominal pain and in some patients, fecal blood. After C. jejuni infection, squeals may occur such as reactive arthritis. The aim of the study was to investigate the frequency of antibodies to the recombinant protein P39 sticks C. jejuni in patients with gastrointestinal disorders and reactive arthritis in Poland. MATERIAL AND METHODS: Serum samples collected from 46 patients with bacteriology confir- med infection caused by Campylobacter jejuni, 472 sera from patients with gastrointestinal disorders, 97 serum samples obtained from patients with reactive arthritis and 84 sera from healthy adults and children. Sera were screened for anti-P39 C. jejuni recombinant protein IgA, IgG andIgM antibodies by using the home-made ELISA. Protein P39 C. jejuni was expressing in E. coli BL21 (DE3) using the pET-30 Ek/LIC expression vector. Purification was accomplished by immobilized metal (Ni2+) affinity column chromatography (His Bind Resign, Novagen). RESULTS: SDS-PAGE and Coomassie brilliant blue staining confirmed a high purity of the recombinant P39 protein preparation with an expected molecular mass of 39 kDa. The results of ELISA with the P39 recombinant protein revealed that IgA antibodies in diagnostically significant level (x + 2SD) were found in 18.8%, IgM in 14.8% and IgG in 7.8% of sera obtained from patients with of gastrointestinal disorders. On the other hand, antibodies to recombinant P39 protein in sera obtained from patients with reactive arthritis were found in more than twice the percentage than in patients with gastrointestinal disorders (IgA in 34.0%, IgG in 26.8% and IgM in 19.6%). CONCLUSIONS: In conclusion, based on the data obtained, C. jejuni may be important factor in triggering the gastrointestinal disorder and reactive arthritis in humans in Poland.
Subject(s)
Antibodies, Bacterial/blood , Arthritis, Reactive/immunology , Bacterial Proteins/immunology , Campylobacter Infections/immunology , Campylobacter jejuni/immunology , Gastroenteritis/immunology , Adolescent , Adult , Antibody Formation , Arthritis, Reactive/blood , Biomarkers/blood , Campylobacter Infections/blood , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Gastroenteritis/blood , Humans , Immunoglobulin A/blood , Immunoglobulin M/blood , Infant , Male , Recombinant Proteins/blood , Young AdultABSTRACT
OBJECTIVES: The pathogenesis of reactive arthritis (ReA) is incompletely understood but may involve aberration(s) in the host's innate immune response towards infecting microbes. We therefore studied the production of interleukin (IL)-1ß, a marker of inflammasome activation, and of IL-6, IL-12, IL-23, and tumour necrosis factor (TNF)-α, promoters of T-cell differentiation, by peripheral blood mononuclear cells (PBMNs) and monocyte-derived macrophages from healthy subjects with a history of ReA. METHOD: The study included 10 human leucocyte antigen (HLA)-B27-positive healthy subjects with previous ReA triggered by Yersinia enterocolitica O:3 infection and 20 healthy reference subjects, of whom 10 were HLA-B27 positive. PBMNs and macrophages were cultured for 18 h with bacterial lipopolysaccharide (LPS), muramyl dipeptide (MDP), Yersinia, or their appropriate combinations. PBMNs were also stimulated with monosodium urate (MSU) crystals. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA) and the Luminex system. RESULTS: IL-1ß secretion was similar from cells of the ReA group and from the HLA-B27-positive and -negative reference groups. TNF-α production from macrophages upon co-stimulation of LPS and MDP increased in the order ReA group < HLA-B27-positive reference group < HLA-B27-negative reference group (p for a trend = 0.027). Similarly, Yersinia-induced TNF-α and IL-23 production increased in the same order (p for trend for TNF-α = 0.036; p for trend for IL-23 = 0.026). CONCLUSIONS: PBMNs and macrophages from healthy subjects with previous ReA show normal inflammasome activation and low TNF-α and IL-23 production. This low cytokine production may impair bacterial elimination and thereby contribute to the triggering of ReA.
Subject(s)
Arthritis, Reactive/blood , HLA-B27 Antigen/immunology , Inflammasomes/metabolism , Interleukin-23/immunology , Yersinia Infections/diagnosis , Adolescent , Adult , Arthritis, Reactive/etiology , Arthritis, Reactive/physiopathology , Biomarkers/metabolism , Child , Cohort Studies , Enzyme Activation , Enzyme-Linked Immunosorbent Assay , Female , HLA-B27 Antigen/metabolism , Humans , Inflammasomes/immunology , Interleukin-12/immunology , Interleukin-12/metabolism , Interleukin-23/metabolism , Interleukin-6/immunology , Interleukin-6/metabolism , Macrophages/immunology , Macrophages/pathology , Male , Prohibitins , Sensitivity and Specificity , Severity of Illness Index , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism , Yersinia Infections/complications , Young AdultABSTRACT
The study analyzed serum hyaluronidase and deoxyribonuclease activity in patients with early arthritis--early rheumatoid arthritis and acute reactive arthritis. The criteria of their differential diagnostics were developed on the basis of data obtained. The genuine methods were applied to analyze hyaluronidase and deoxyribonuclease activity of blood serum based on formation of clot of etacridine acetate (rivanol) with hyaluronic acid and DNA inversely proportionally to their polymerization under the impact of enzymes. The increased serum hyaluronidase and deoxyribonuclease activity was established in patients with early arthritis as compared with control group (p < 0.001). The prevalence of mentioned types of activity under early rheumatoid arthritis as compared with acute reactive arthritis was detected too. The rests for differentiate diagnostics of early rheumatoid arthritis and acute reactive arthritis were developed conformed to criteria of the most useful diagnostic tests in rheumatology.
Subject(s)
Arthritis, Reactive , Arthritis, Rheumatoid , Deoxyribonucleases/blood , Hyaluronoglucosaminidase/blood , Arthritis, Reactive/blood , Arthritis, Reactive/diagnosis , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Diagnosis, Differential , Humans , ROC CurveABSTRACT
INTRODUCTION: After exclusion of reactive, psoriatic and enteritis-associated arthritis, a group of "undifferentiated" peripheral spondyloarthritis (pSpA) remains. This group shares genetics, T-cell repertoire, and cytokines with reactive arthritis (ReA). ReA is preceded by gut or urogenital infection. Otherwise the two may be similar. We know little of the metabolic pathways driving undifferentiated pSpA or ReA. Nuclear magnetic resonance (NMR)-based metabolomics presents a hypothesis-free approach to study and compare metabolic pathways driving undifferentiated pSpA and ReA. METHODS: Serum and synovial fluid metabolomes of 19 ReA and 13 undifferentiated pSpA, and serum metabolome of 18 controls were profiled using 1 H-based NMR. Partial least square-discriminant analysis (PLS-DA) identified metabolites different in patients as compared to controls. Multivariate analysis confirmed these. Altered metabolic pathways were identified using metabolites set enrichment analysis (MSEA). The serum and synovial fluid metabolomes of ReA and undifferentiated pSpA were compared. RESULTS: Ten serum metabolites of ReA/undifferentiated pSpA were different from those of controls. Six metabolites were different between serum and synovial fluid of these patients. MSEA identified five pathways different between patients and controls, and five pathways different between serum and synovial fluid of patients. PLS-DA showed no difference between the metabolomes of serum or of synovial fluid between ReA and undifferentiated pSpA. DISCUSSION: Identified metabolic pathways may be explored further to understand the pathogenesis and to target therapeutics. The similar immuno-metabolic pathways suggest similar pathogenesis of ReA and undifferentiated pSpA. Thus, they should be studied as a single disease entity.
Subject(s)
Arthritis, Reactive/blood , Metabolomics/methods , Proton Magnetic Resonance Spectroscopy , Spondylarthropathies/blood , Synovial Fluid/metabolism , Adult , Arthritis, Reactive/diagnosis , Biomarkers/blood , Case-Control Studies , Female , Humans , Male , Predictive Value of Tests , Prohibitins , Spondylarthropathies/diagnosis , Young AdultABSTRACT
We report here on four cases of patients with strongly positive anti-citrullinated cyclic peptides (anti-CCP) antibodies and clinical features of seronegative spondyloarthritis (SpA) and reactive arthritis. The four patients had various clinical presentations: one had an initial diagnosis of seropositive rheumatoid arthritis (RA) with involvement of the sacroiliac joints (similar to previous reports of the association of two diseases); one had a clinical picture of reactive arthritis following an episode of an Escherichia coli positive urinary tract infection; and two had asymmetrical sacroiliitis (SII), but no evidence of peripheral joint involvement (never reported before). In all cases, high titers of anti-CCP antibodies were found. We present a comparison of the clinical manifestations, radiographic features and treatment regimens of these cases. Our report supports previous literature data of possible overlap existing between RA and SpA, but also presents for the first time the association of high titers of anti-CCP antibodies with SII and reactive arthritis in patients with no peripheral small joint involvement.
Subject(s)
Anti-Citrullinated Protein Antibodies/blood , Arthritis, Reactive/immunology , Escherichia coli Infections/immunology , Sacroiliitis/immunology , Urinary Tract Infections/immunology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Reactive/blood , Arthritis, Reactive/diagnostic imaging , Arthritis, Reactive/microbiology , Biomarkers/blood , Escherichia coli Infections/diagnosis , Escherichia coli Infections/microbiology , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Sacroiliitis/blood , Sacroiliitis/diagnostic imaging , Sacroiliitis/microbiology , Serologic Tests , Treatment Outcome , Up-Regulation , Urinary Tract Infections/diagnosis , Urinary Tract Infections/microbiology , Young AdultABSTRACT
OBJECTIVE: To determine the causative role of human parvovirus B19 as a preceding infection in patients examined for acute reactive arthritis (ReA). METHODS: Sixty adult patients with acute arthritis were screened for evidence of triggering infections. In all patients, cultures of stool specimens and of Chlamydia trachomatis in urethra/cervix, and/or bacterial serology were studied. The timing of primary infection of human parvovirus B19 was determined by measurement in serum of VP2-IgM, VP2-IgG, epitope-type specifity of VP2-IgG, and avidity of VP1-IgG. RESULTS: Median time from onset of joint symptoms to the rheumatological consultation was five weeks (range 1-62). Of the 60 patients, 35 fulfilled the diagnostic criteria for ReA; in the remaining, the diagnosis was unspecified arthritis (UA). Thirty-six patients had antibodies for the B19 virus. Occurrence of these antibodies did not differ significantly between ReA and UA groups (P = 0.61). Of these 36 patients, 34 had a pre-existing immunity to the B19 virus. Of the two other patients, one had rash and self-limiting polyarthritis with serological evidence of B19 primary infection, and the other had arthritis of the lower extremities with serological evidence of a convalescence period after the B19 primary infection. The latter patient also had antibodies to Yersinia, with a clinical picture typical for ReA. CONCLUSION: In patients examined for acute ReA, the frequency of recent B19 virus infection was 3.3% (2 out of 60). The diagnostic utility of the presented methodology, by using a single serum sample, was evident.
Subject(s)
Antibodies, Viral/blood , Arthritis, Reactive/immunology , Arthritis, Reactive/virology , Parvoviridae Infections/complications , Parvoviridae Infections/diagnosis , Parvovirus B19, Human/immunology , Acute Disease , Adult , Arthritis, Reactive/blood , Combinatorial Chemistry Techniques , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Incidence , Male , Middle Aged , Parvoviridae Infections/immunology , Prohibitins , Serologic Tests/methodsABSTRACT
The term 'reactive arthritis' was first used in 1969 to describe the development of sterile inflammatory arthritis as a sequel to remote infection, often in the gastrointestinal or urogenital tract. The demonstration of antigenic material (e.g. Salmonella and Yersinia lipopolysaccharide), DNA and RNA, and, in occasional cases, evidence of metabolically active Chlamydia spp. in the joints has blurred the boundary between reactive and post-infectious forms of arthritis. No validated and generally agreed diagnostic criteria exist, but the diagnosis of reactive arthritis is mainly clinical based on acute oligoarticular arthritis of larger joints that develops within 2-4 weeks of the preceding infection. In about 25% of patients, the infection can be asymptomatic. Diagnosis of the triggering infection is very helpful for the diagnosis of reactive arthritis. This is mainly achieved by isolating the triggering infection (stools, urogenital tract) by cultures (stool cultures for enteric microbes) or ligase reaction (Chlamydia trachomatis). However, after the onset of arthritis, this is less likely to be possible. Therefore, the diagnosis must rely on various serological tests to demonstrate evidence of previous infection, but, these serological tests are unfortunately not standardized. Treatment with antibiotics to cure Chlamydia infection is important, but the use of either short or prolonged courses of antibiotics in established arthritis has not been found to be effective for the cure of arthritis. The long-term outcome of reactive arthritis is usually good; however, about 25-50% of patients, depending on the triggering infections and possible new infections, subsequently develop acute arthritis. About 25% of patients proceed to chronic spondyloarthritis of varying activity.
Subject(s)
Arthritis, Reactive/diagnosis , Bacterial Infections/diagnosis , Arthritis, Reactive/blood , Arthritis, Reactive/microbiology , Bacterial Infections/blood , Bacterial Infections/microbiology , Humans , Serologic TestsABSTRACT
OBJECTIVE: Analysis of cytogenetic alterations in peripheral blood lymphocytes (PBL) of patients with acute and chronic reactive arthritis (AcReA and ChrReA) and rheumatoid arthritis (RA). METHODS: The frequencies of sister chromatid exchanges (SCE) and cell proliferative abilities were analysed in PBL from 69 patients with arthritis and 30 healthy controls. The analyses were done on metaphase chromosomes from PBL grown in cell culture for 72 hours. Cytogenetic parameters were compared among study groups and correlations with different clinical, immune and demographic characteristics were analysed. RESULTS: No significant increases in the frequencies of SCE were detected in PBL from patients with AcReA, ChrReA and RA as compared to controls. However, marked impairment of cell proliferative abilities was detected in cultured lymphocytes from patients with arthritis as compared to healthy controls. Significant associations between measures of disease activity and proliferative abilities of PBL were established. Parameters of lymphocyte proliferation were also influenced by concentration of anti-inflammatory cytokine interleukin-10 in the blood of patients. CONCLUSION: No increased risk of genetic alterations as measured by the rate of SCE was found in patients with RA and ReA. It is most likely that impaired proliferative abilities of peripheral blood lymphocytes are related to disease activity and could reflect systemic changes in cytokines production and intracellular signal transduction.
Subject(s)
Arthritis, Reactive/blood , Arthritis, Rheumatoid/blood , Cell Proliferation , Lymphocyte Activation/genetics , Lymphocytes/physiology , Sister Chromatid Exchange/genetics , Acute Disease , Adult , Case-Control Studies , Cells, Cultured , Chromosome Aberrations , Chronic Disease , Demography , Female , Humans , Interleukin-10/metabolism , Male , Middle Aged , ProhibitinsABSTRACT
BACKGROUND: Reactive arthritis (ReA) has been sporadically reported as triggered by Mycoplasma pneumoniae. This study examined the potential relationship between the acute M. pneumoniae infection and juvenile spondyloarthropathy (jSpA) in children. PATIENTS AND METHODS: Twelve patients with ReA secondary to acute M. pneumoniae were examined. M. pneumoniae-specific IgM, IgG and IgA antibodies were serologically confirmed by enzyme-linked immunosorbent assay (ELISA) tests (Savyon Diagnost., Israel). Due to the early appearance and relatively short life time of M. pneumoniae-specific IgM antibodies, their detection allowed the diagnosis of acute infection using single serum sample, confirmed by parallel serum in 7 of 12 patients. Specific IgM and IgG titers higher than 10 U/l were considered positive and those higher than 50 U/l as highly positive. Specific IgA antibodies were detected in only one patient. RESULTS: Four patients were female and eight were male. The mean age at onset was 9 years, and the mean duration of follow-up was 24.1 months (range 18-32). The mean number of involved joints was 2.8, and the knee joints were involved in 7 of 12 patients. The mean recovery time was 4.5 weeks (range 1-28) in eight reactive arthritis (ReA) cases; three patients developed enthesitis-related arthritis, and in one patient, genuine juvenile ankylosing spondylitis (jAS) was diagnosed. Two patients were HLA-B27-positive, and one patient was HLA-B7/B27-positive. Six patients had preceding respiratory symptoms, and five were treated with antibiotics. CONCLUSIONS: Our findings provide clear evidence of ReA diagnosis following an acute M. pneumoniae infection that in four patients progressed to chronic jSpA. Our results suggest that detecting M. pneumoniae-specific antibodies in serological screening of jSpA patients might be useful. It is presently unclear whether antibiotic treatment would change the disease course in those patients.
Subject(s)
Arthritis, Reactive/complications , Arthritis, Reactive/diagnosis , Mycoplasma pneumoniae/immunology , Pneumonia, Mycoplasma/complications , Spondylarthropathies/complications , Spondylarthropathies/diagnosis , Age of Onset , Arthritis, Reactive/blood , Child , Chronic Disease , Female , Follow-Up Studies , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Male , Pneumonia, Mycoplasma/blood , Prohibitins , Serologic Tests , Spondylarthropathies/bloodSubject(s)
Antitubercular Agents/therapeutic use , Arthritis, Reactive , Tuberculosis, Pulmonary , Adolescent , Arthritis, Reactive/blood , Arthritis, Reactive/diagnosis , Arthritis, Reactive/drug therapy , Arthritis, Reactive/etiology , Arthritis, Reactive/physiopathology , Female , Hand Joints/pathology , Humans , Knee Joint/pathology , Length of Stay , Serologic Tests , Treatment Outcome , Tuberculin Test , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/physiopathologyABSTRACT
Infectious agents were detected in 100% of examined children with Reiter's disease (RD). Chlamydia trachomatis were detected in 98% of cases. In children with RD lesions of joints and eyes often took acute forms with cases of sacroiliitis, early muscular atrophy and conjunctivitis. In 95% of the patients the prostatitis manifestations were detected. In children with RD a rised number of CD lymphocytes in combination with the fivefold rised IL-4 content, an essential increase in the activity of C2-C5 components of the complement and a multiple rised level of PSA were registered.
Subject(s)
Arthritis, Reactive , Chlamydia trachomatis/isolation & purification , Adolescent , Arthritis, Reactive/blood , Arthritis, Reactive/immunology , Arthritis, Reactive/microbiology , Arthritis, Reactive/pathology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , Child , Child, Preschool , Complement System Proteins/immunology , Female , Humans , Interleukin-4/blood , Male , Prostate-Specific Antigen/blood , Prostatitis/blood , Prostatitis/pathology , Sacroiliac Joint/pathologyABSTRACT
Spondyloarthritidies represent a group of conditions affecting the axial and peripheral muscoloskeletal apparatus and are often associated with psoriasis, infections, and inflammatory bowel diseases. Other diseases included in this category are psoriatic arthritis, ankylosing spondylitis, and enteropathic arthritis. Reactive arthritis is an elusive spondyloarthritis, commonly occurring 1 to 3 weeks after a digestive or a genitourinary tract infection, in which microorganisms do not infect the joint directly. Reactive arthritis is classically characterized by large-joint arthritis, urethritis in men and cervicitis in women, and eye inflammation (usually conjunctivitis or uveitis) but encompasses numerous other symptoms and signs, including manifestations of dermatologic interest such as keratoderma blenorrhagicum and circinate balanitis. The diagnosis of reactive arthritis is clinical, and the infectious agent cannot always be identified due to disease latency after the infection. Most cases are self-limiting, but reactive arthritis may become chronic in 30% of cases. Treatment options include anti-inflammatory drugs, steroids, and sulfasalazine; biologic agents, such as tumor necrosis factor α (TNF-α) blockers, have been recently used, but there are only a few randomized clinical trials on the treatment of reactive arthritis. The effectiveness of antimicrobials needs further evaluation.
Subject(s)
Arthritis, Reactive/complications , Skin Diseases/etiology , Spondylarthritis/complications , Antibodies/blood , Arthritis, Reactive/blood , Humans , Spondylarthritis/bloodABSTRACT
Endomorphin (EM)-1 and EM-2 are opioid tetrapeptides recently located in the central nervous system and immune tissues with high selectivity and affinity for the mu-opioid receptor. Intracerebroventricular (i.c.v.) administration of morphine stimulates the hypothalamo-pituitary-adrenal (HPA) axis. The present study investigated the effect of centrally administered EM-1 and EM-2 on HPA axis activation. Rats received a single i.c.v. injection of either EM-1 (0.1, 1.0, 10 microg), EM-2 (10 microg), morphine (10 microg), or vehicle (0.9% saline). Blood samples for plasma corticosterone determinations were taken immediately prior to i.c.v. administration and at various time points up to 4 h post-injection. Trunk blood, brains and pituitaries were collected at 4 h. Intracerebroventricular morphine increased plasma corticosterone levels within 30 min, whereas EM-1 and EM-2 were without effect. In addition, pre-treatment of i.c.v. EM-1 did not block the rise in corticosterone after morphine. Corticotrophin-releasing factor (CRF) mRNA and arginine vasopressin (AVP) mRNA in the paraventricular nucleus (PVN) and POMC mRNA in the anterior pituitary were found to be unaffected by either morphine or endomorphins. Since release of other opioids are elevated in response to acute stress, we exposed rats to a range of stressors to determine whether plasma EM-1 and EM-2 can be stimulated by HPA axis activation. Plasma corticosterone, ACTH and beta-endorphin were elevated following acute restraint stress, but concentrations of plasma EM-1-immunoreactivity (ir) and EM-2-ir did not change significantly. Corticosterone, ACTH and beta-endorphin were further elevated in adjuvant-induced arthritis (AA) rats by a single injection of lipopolysaccharide (LPS), but not by restraint stress. In conclusion, neither EM-1 or EM-2 appear to influence the regulation of the HPA axis. These data suggest that endomorphins may be acting on a different subset of the mu-opioid receptor than morphine. The failure to induce changes in plasma EM-ir in response to the chronic inflammatory stress of AA, the acute immunological stress of LPS, or the psychological stress of restraint, argues against an important role for endomorphins in mediating HPA axis activity.
Subject(s)
Hypothalamo-Hypophyseal System/drug effects , Oligopeptides/pharmacology , Pituitary-Adrenal System/drug effects , Receptors, Opioid, mu/agonists , Adrenocorticotropic Hormone/blood , Analysis of Variance , Animals , Arthritis, Reactive/blood , Chromatography, High Pressure Liquid , Corticosterone/blood , Hypothalamo-Hypophyseal System/metabolism , In Situ Hybridization/methods , Lipopolysaccharides/pharmacology , Male , Morphine , Oligopeptides/blood , Pituitary-Adrenal System/metabolism , Radioimmunoassay/methods , Rats , Rats, Sprague-Dawley , Stimulation, Chemical , Stress, Psychological , beta-Endorphin/bloodABSTRACT
OBJECTIVE: To assess the incidence of Reiter's syndrome aboard The Golden Venture, a ship carrying illegal immigrants from China to the United States. METHODS: After identification of an index case, we conducted telephone interviews with medical staff at immigrant detention centers in Pennsylvania, New York, and Virginia. When a potential case was identified at one facility, we performed a site inspection, reviewing the medical records of all detainees and performing histories and physicals on all those with joint and/or ocular complaints. RESULTS: We identified two patients, both HLA B27 positive, with Reiter's syndrome. The observed incidence (0.87%) approximated the predicted incidence but may have underestimated the actual incidence. We review the history of shipboard Reiter's syndrome, and discuss the pathogenic roles of HLA B27 and particular infectious agents. CONCLUSION: Continued transportation of illegal immigrants from China and other parts of the world is likely to result in occasional clusters of Reiter's syndrome. Physicians treating immigrant populations should remain aware of the possibility of reactive arthritis.
Subject(s)
Arthritis, Reactive/epidemiology , Disease Outbreaks , Emigration and Immigration , Adult , Arthritis, Reactive/blood , Arthritis, Reactive/pathology , Crime , HLA-B27 Antigen/blood , Humans , Incidence , Male , Ships , Syndrome , Synovial Membrane/pathology , United States/epidemiologyABSTRACT
Reactive arthritis (ReA) and rheumatoid arthritis (RA) are inflammatory joint diseases which differ in several clinical and immunological aspects. In both diseases locally activated T cells are considered important for pathogenesis. Subsets of T cells are demonstrated by staining with monoclonal antibodies recognizing isotypes of the common leukocyte antigen: CD45RA, which is considered to be a marker of native T cells, and CD45RO a marker of primed T cells; a third subset was also identified according to the staining intensity of CD45RB: CD45RBbright and CD45RBdim. The expression of these and the surface markers CD3, CD4, CD8, CD14 and CD56 was studied in synovial fluid (SF) and peripheral blood (PB) of patients with ReA (n = 11), RA (n = 10) and normal controls (n = 10) by three-colour immunocytometry. Significantly more CD45RBbright were found in the PB of patients with ReA (64.1%) and RA (63.5%) than in the SF of ReA (36.8%) and RA (40.6%) patients. However, when analyzed in relation to CD45RO, the CD45RO/CD45RBbright population was not significantly different between the SF and PB of patients with ReA (32.2% vs. 26.8%) and RA (30.6% vs. 28.1%), respectively. Among the three cellular subtypes of CD4+ lymphocytes demonstrated in this study (CD45RA/RBbright, CD45RO/CD45RBbright and CD45RO/CD45RBdim) none, in contrast to previous results of other groups, showed marked differences between ReA and RA in either of the compartments examined.
Subject(s)
Arthritis, Reactive/immunology , Arthritis, Rheumatoid/immunology , CD4 Antigens/analysis , Leukocyte Common Antigens/analysis , Synovial Fluid/immunology , T-Lymphocyte Subsets/immunology , Adolescent , Adult , Aged , Arthritis, Reactive/blood , Arthritis, Rheumatoid/blood , Female , Flow Cytometry/methods , Humans , Male , Middle Aged , ProhibitinsABSTRACT
OBJECTIVE: The assay for the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) has been shown to reflect increased type I collagen degradation in patients with rheumatoid arthritis. To look for increased collagen degradation in other inflammatory rheumatic diseases, we studied plasma ICTP in patients with reactive arthritis (ReA). METHODS: ICTP was determined by radioimmunoassay from 69 ReA patients. ICTP data on 56 patients aged > or = 20 years were compared with normal ICTP values available for that age group. RESULTS: The median (range) plasma ICTP concentration of the patients > or = 20 years of age was 3.9 (2.1-9.6) micrograms/l, and in 13 (23%) of them the value was elevated if compared with the normal upper reference limit (mean + 2SD), 5.2 micrograms/l, given by the manufacturer. The mean (SD) duration of joint symptoms was 76 (61) days in patients with ReA. Modest albeit statistically significant correlations were noted between the plasma ICTP and the erythrocyte sedimentation rate, C-reactive protein and the Lansbury articular index (Spearman's r 0.39, 0.37 and 0.29, respectively). The median values for all of the above mentioned parametres were at least twice as high in the group of patients with elevated ICTP compared with those in patients with normal values (p < 0.05). No statistically significant correlation was detected between the plasma ICTP and the duration of joint symptoms. CONCLUSION: Increased type I collagen degradation can take place in ReA, and this process seems to correlate with the extent and activity of the joint disease.