Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis

OBJECTIVE: To measure gut immunity directly in jejunal fluid in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). METHODS: Antibodies against three different Enterobacterias were measured in jejunal perfusion fluids (collected by a double balloon perfusion device) of 19 patients with AS, 14 patients with RA, and 22 healthy controls using enzyme linked immunosorbent assay. RESULTS: The AS patients had significantly increased jejunal fluid concentrations of IgM, IgG, and IgA class antibodies against Klebsiella pneumoniae, and IgM and IgA class antibodies against Escherichia coli and Proteus mirabilis compared with healthy controls. When compared with the patients with RA, the AS patients had higher concentrations of IgA and IgG class antibodies only against K pneumoniae. The RA patients had higher IgM class antibody concentrations against all three studied Enterobacterias, when compared with the healthy controls, suggesting an enhanced mucosal immune response in these patients. A three month treatment with sulphasalazine did not decrease enterobacterial antibody concentrations in the 10 patients with AS. CONCLUSION: There is strong direct evidence for an abnormal mucosal humoral immune response particularly to K pneumoniae in patients with AS.     

Rheumatoid arthritis and ankylosing spondylitis

Povidone-iodine is the cleansing agent most commonly used before accessing implanted venous devices. This agent has peak bacteriocidal action when allowed to air-dry for 20 min postscrub. However, the drying time increases the length of the procedure and the risk for accidental contamination of the site. In this study, the effectiveness of air drying versus blot drying povidone-iodine-prepared skin sites was compared by examining the number of bacterial colonies present on skin cultures obtained after each drying method. No significant differences in the number of bacterial colonies between the two drying methods were found.     

Collagen-specific cytotoxic T lymphocyte responses in patients with ankylosing spondylitis and reactive arthritis

Both ankylosing spondylitis (AS) and reactive arthritis (ReA) are strongly associated with HLA-B27 although the mechanism for this association is still unknown. Here we examine the hypothesis that B27-restricted, joint antigen-specific cytotoxic T lymphocytes (CTL) may be the driving force of AS and ReA. Type II and type XI procollagens (CII and CXI, respectively), expressed almost exclusively in the articular cartilage of the joints, were chosen as the possible targets of autoimmune CTL. Type I procollagen (CI), expressed in many different tissues, was also included as control. Nineteen nonamer peptides bearing appropriate HLA-B27 binding motifs from human CI, CII and CXI were identified and synthesized. When analyzed for binding affinity to HLA-B27 in assembly assays, four (two from CII, two from CXI) were found capable of binding to HLA-B27 with high affinity. These B27-binding collagen peptides were then used to stimulate peripheral blood lymphocytes from eight B27-positive AS and three ReA patients for identification of possible B27-restricted autoimmune CTL. HLA-B27-restricted CTL specific for one of the CII peptides, P109 were found in one of the ReA patients, but in none of the others.     

Etiopathogenesis of ankylosing spondylitis and reactive arthritis

In ankylosing spondylitis and reactive arthritis, an interplay of microbe and major histocompatibility complex initiates a sequence of events resulting in chronic inflammation. With the use of molecular probes as direct evidence and immune response patterns as indirect evidence, a strong case has been made for a central role of local microbial antigen in reactive arthritis. Cofactors such as gender, persistent gut inflammation, and antibiotic treatment may contribute to this process. Studies of transgenic rats and of familial spondylitis implicate B27 itself as the critical host variable. The results of recent studies point to intimate B27-bacteria interrelationships. HLA-B27 and proteins from enteric bacteria are structurally related, in a manner that may affect T cell response to enteric pathogens. B27 also may directly affect host-microbe interactions by modulating the invasive potential of these bacteria into target cells. Studies are in progress to apply the predictions of these in vitro systems to the in vivo situations of these diseases. The insights of research in the spondyloarthropathies may find broad applications in the rheumatic diseases.     

Clinical comparison of patients with ankylosing spondylitis, Reiter's syndrome and psoriatic arthritis

Between 1976 and 1989, 160 cases of seronegative spondyloarthropathy (SNSA) were admitted to the Department of Medicine at Chulalongkorn Hospital. The prevalence of idiopathic ankylosing spondylitis (IdAS) was 52 cases (32.5%), Reiter's syndrome (RS) 68 cases (42.5%), psoriatic arthritis (PsA) 28 cases (17.5%), reactive arthritis eight cases (5.0%) and Behcet's disease four cases (2.5%). Clinical comparison of the patients with IdAS, RS and PsA showed a male predominance in IdAS (90.2%), RS (97.1%) and PsA (71.4%). There was a significant difference (p < 0.01) between IdAS and PsA, and RS and PsA. The initial articular manifestation usually occurred in the younger age group (IdAS, 22.15; RS, 22.91; and PsA, 30.86 years); however, there was a significant difference (p < 0.05) between IdAS and PsA, and RS and PsA. Initial peripheral arthritis was found in IdAS (51.9%), RS (91.2%) and PsA (92.6%); there was a significant difference (p < 0.001) between IdAS and RS, and IdAS and PsA. The symptom of back pain was found in IdAS (78.8%), RS (38.2%) and PsA (21.4%); there was a significant difference (p < 0.001) between IdAS and RS, and IdAS and PsA. During physical examination, peripheral arthritis was evident in the IdAS (42.2%), RS (88.2%) and PsA (92.2%) patients; likewise sacroiliitis was found in the IdAS (100%) RS (54.4%), and PsA (57.2%) patients. Evidence of ankylosing spondylitis was found in the IdAS (100%), RS (22.1%) and PsA (46.4%) patients. These findings show a significant difference (p < 0.001) between patients with IdAS and RS, IdAS and PsA. Other associated symptoms were similar, particularly evidence of enthesopathy (tendonitis, heel pain, plantar fasciitis), the polyarticular pattern was more common than the mono-articular pattern. Hip joint was significantly (p < 0.05) more commonly involved in patients with IdAS than in those with RS and PsA. Associated symptoms, particularly genital lesion or skin lesion, are specific symptoms for RS and PsA, respectively.     

Antibodies to Klebsiella pneumoniae lipopolysaccharide in patients with ankylosing spondylitis

The role of microbial lipopolysaccharides (LPS) in the aetiopathogenesis of ankylosing spondylitis (AS) is a matter of continuing debate. In this study, class-specific IgG, IgA and IgM antibodies against Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Salmonella enteritidis LPS were measured by enzyme-linked immunosorbent assay (ELISA) in 100 AS patients, 50 rheumatoid arthritis (RA) patients and 50 healthy control subjects. The AS patients had significantly elevated levels of IgG and IgA antibodies against K. pneumoniae LPS (P < 0.001) and IgA antibodies against E. coli LPS (P < 0.05) compared to healthy controls. There were no significant elevations of antibody levels against S. typhimurium and S. enteritidis in the three study groups. In addition, there was a correlation between IgG and IgA anti-K. pneumoniae LPS antibody levels and the acute-phase reactant C-reactive protein (P < 0.001).     

Quality of life in patients with ankylosing spondylitis

Quality of life encompasses the net effects that a patient perceives an illness to have on his or her life. Quality of life commonly includes symptoms, physical functioning, work ability, social interaction, psychological functioning, treatment side effects, and financial costs. In ankylosing spondylitis, although symptoms of pain, stiffness, and fatigue are common and moderately severe, few patients develop severe functional disability and most remain employed. The limited information available suggests that most patients with ankylosing spondylitis have few problems with social interactions, although depression is not uncommon. Direct medical costs of ankylosing spondylitis are low, compared with those of other rheumatic diseases.     

Prevalence of antiphospholipid antibodies in patients with ankylosing spondylitis

OBJECTIVE: To establish the prevalence of antiphospholipid antibodies (aPL) in a group of patients with ankylosing spondylitis (AS). The relation of the antibodies with different clinical and analytical features was studied. METHODS: Eighty-four patients with AS (71 men) and 40 age and sex matched controls were studied. aPL determinations included: anticardiolipin antibodies (aCL) of the IgM, IgG, and IgA classes, the presence of lupus anticoagulant (LAC), and a false positive serologic test for syphilis. Comparisons between variables were done by Student t test, Mann-Whitney test and Chi squared test. Correlations between aPL and clinical variables were performed by Pearson coefficients. RESULTS: Twenty-four patients with AS (29%) has positive IgG aCL, compared with only 2 cases in the control group (5%) (p < 0.002). There were no differences in other aPL determinations between patients and controls. There was no correlation between the presence of aCL (IgG, IgM, or IgA) and LAC and the different aspects of the disease. Two patients fulfilled the criteria for antiphospholipid syndrome. CONCLUSION: Our results indicate the presence of IgG aCL in patients with AS higher than in the normal population but their relation with thrombosis and other systemic manifestations seems weak.     

Cardiac impairment detected by echocardiography in patients with ankylosing spondylitis

The authors subjected to complete echocardiographic examination 40 patients with ankylosing spondylitis (AS) in order to assess pathological changes of the heart (changes of the structure and function of valves, myocardial function of the left ventricle and the pericardium) and compare their incidence with clinical characteristics of the patients (age, duration, stage, form and activity of the disease) as well as with the presence of ECG changes. Based on the results and their statistical analysis they revealed that structural changes of the aorta and its valves associated with dilatation of the root of the aorta, its mild insufficiency and the possible finding of a typical bump on its posterior wall is found in half the patients with AS, being more frequent when the disease develops early, when it persists for a long time or is in an advanced stage. A similar relationship is found also in the presence of mild diastolic dysfunction of the left ventricle. The authors did not observe a more frequent incidence of other pathological changes of the heart in patients with AS. None of the detected changes were clinically severe and did not call for aimed treatment or surgery. In the conclusion the authors compare the assessed facts with data in the literature and confront data in the literature.     

Ultrastructural changes in articular cartilage in rheumatoid arthritis

Electron microscope studies of the articular cartilages removed in the course of the operation on 6 patients with rheumatoid arthritis were carried out. The processes of destruction of chondrocytes and the cartilaginous matrix in different regions of the articular cartilage were traced. In the surface areas of the drastically changed cartilage there were observed leucocytes of the synovial fluid, and in deeper areas--disintegration of chondrocytes and extracellular disposition of lysosomes and altered organellas, destroyed cartilaginous cells. In these areas destruction of collagenous fibres was particularly intensive. In areas of the tissue remote from the destuction hypertrophy of chondrocytes due to hyperplasia of various organellas and the Golgi complex in particular were noted. In the Golgi zone granules of glycogen were detected. No mitoses were observed. Apparently, the enzymatic destruction of the cartilaginous matrix in rheumatoid arthritis could proceed at the expense of the activazation of the synovial fluid lysosomes and lysosomes of chondrocytes themselves. A reparative regeneration of the disintegrating matrix was realized mainly because of hypertrophy of the functionally preserved chondrocytes.     

Serum testosterone levels are not elevated in patients with ankylosing spondylitis

OBJECTIVE: Studies in patients with ankylosing spondylitis (AS) describe slightly elevated serum testosterone levels, but these studies were not properly controlled for possible confounders. METHODS: In a case-control study serum levels of sex steroids, luteinizing hormone, and sex hormone binding globulin (SHGB) were measured in patients with AS and in age and sex matched controls. The body mass index, smoking status, use of alcohol, and fat intake were recorded. RESULTS: Testosterone levels measured in serum extracts did not differ in 50 male patients with AS compared to controls (mean +/- SD 16 +/- 4 vs 15 +/- 5 nmol/l, respectively; p = 0.54). In unextracted serum, however, male patients showed elevated testosterone (p < 0.001) and dehydroepiandrosterone sulfate levels (p = 0.003), even after controlling for confounders (p < 0.001). One of 10 female patients had an elevated testosterone level in unextracted serum. The 17 male users and one of the 2 female users of phenylbutazone had the highest testosterone levels in unextracted serum, and all showed a significant decline after extraction. Serum levels of other sex steroids, luteinizing hormone, and SHGB did not differ significantly between patients and controls. CONCLUSION: Serum testosterone levels are not elevated in male patients with AS. Spuriously elevated testosterone levels in unextracted serum might be related to the use of phenylbutazone in our patient sample.     

Disability in ankylosing spondylitis

PURPOSE: This study was designed to examine the functional loss in ankylosing spondylitis and explore the relationship between disability and various factors such as age, disease duration, disease activity, spinal mobility, chest expansion, peripheral joint involvement, radiological changes, and psychosocial well-being. METHOD: Forty-two patients were included in this cross-sectional study. RESULTS: The results showed that 37 patients had mild to moderate disability, two patients had severe disability, and three patients did not report any functional loss. Spearman correlation analyses showed that disability was strongly correlated with spinal mobility measures, disease activity measures, and disease duration. Also, patients with peripheral joint involvement had greater disability. When the predictive effect of five independent variables was studied by multiple regression analysis, it was found that the most powerful predictors of functional loss in AS patients were cervical rotation, modified Schober's test, and pain. CONCLUSIONS: These data suggest that functional consequences of AS are constituted by multiple impairments and each needs to be managed by an integrated physiatric approach.     

Chloroquine retinopathy in patients with rheumatoid arthritis

The paper presents data on the differential fertility of schizophrenics and controls, and the fertility of their siblings. This study used several methodological procedures in the study of schizophrenia reproduction, which strengthens the validity of the findings. Firstly, both male and female rates were examined. Secondly, the method of selection of a control avoided the biases introduced by using census data or other non-matched controls. Third, a diagnostic criterion was used which minimizes the possibility of the inclusion of other psychiatric illnesses. The results obtained support prior reports of the lowered reproductive rates of schizophrenics. Further, the siblings of schizophrenics were found not to have a reproductive advantage when contrasted to control siblings. The failure to find a reproductive advantage conflicts with a hypothesis of a balanced polymorphism as the mechanism maintaining an apparent constant rate of schizophrenia.     

HLA-DM polymorphisms in patients with rheumatoid arthritis

OBJECTIVE: To investigate the contribution of HLA-DMA and DMB genes, which play a crucial role in the HLA class II restricted antigen presentation pathway, in susceptibility to rheumatoid arthritis (RA). METHODS: The distribution of DMA and DMB alleles was examined in patients with RA and in healthy subjects by oligotyping of PCR amplified genomic DNA with sequence specific oligonucleotide probes. RESULTS: There were no significant differences in the prevalence of DMA and DMB alleles in patients with RA as compared to healthy controls. In addition, no significant differences in frequencies of DMA and DMB alleles were observed in RA susceptibility epitope positive RA patients and controls. CONCLUSION: DMA and DMB genes do not appear to play a role in susceptibility to RA.     

Ankle arthrodesis in patients with rheumatoid arthritis

The results of 26 ankle arthrodeses performed for rheumatoid arthritis on 21 patients were reviewed. Tibiotalar arthrodesis was performed in 14 ankles, and tibiotalocalcaneal arthrodesis was performed in 12. External fixation was used in 20 ankles, and internal fixation was used in six. Followup was available in 24 of 26 ankles (19 patients), and averaged 5 years (range, 2-8 years). There was no pain experienced in 19 ankles; mild, occasional pain was experienced in four ankles; and moderate, daily pain was experienced in one ankle. Daily activities were limited in five patients and recreational activities were limited in 11. All patients reported some difficulty walking on uneven terrain. Nearly all patients were satisfied; two were satisfied with reservations and two were dissatisfied. Union was achieved in 25 of 26 (96%) ankles. Ankle arthrodesis is an effective operation in patients with rheumatoid arthritis. Unlike previous reports, union and complication rates in this series were comparable with rates for arthrodesis for posttraumatic and degenerative arthritis.     

Lymphocyte depletion in patients with rheumatoid arthritis

Sixteen patients with severe rheumatoid arthritis, marked inflammation of the synonvial membrane and high rheumatoid titer were cannulated by the thoracic duct for a period rangin between 82 up to 100 days. The patients being not under any medication during that time. Quantitative and qualitative analysis of the lymphocytes were performed, as well as responses to mitogens, rheumatoid factor, circulating antibodies and delayed hypersensitivity. By the 14th day nearly all the patients had a partial or almost complete remission of their disease. No complications were observed. These results will be discussed.