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Biomedical subjects

A Ebringer

Publications and source records attributed to A Ebringer.

At least 55 records · Page 3Linked to original sources

Serum IgA anti-Klebsiella antibodies in ankylosing spondylitis patients from Catalonia.

IgA antibodies against Klebsiella pneumoniae were measured by immunofluorescence in 84 Catalan patients with ankylosing spondylitis (AS), 41 patients with non-inflammatory arthropathies (NIA) and 22 patients with rheumatoid arthritis (RA). Patients with AS showed higher levels of anti-klebsiella IgA antibodies (IgA-Kp) than NIA and RA patients (4.7 +/- 1.6 U vs 3.7 +/- 1.5 U and 3.1 +/- 1.4 U respectively, p = 0.001). In AS patients a significant correlation between IgA-Kp and levels of C-reactive protein was observed. Although no clear correlation was found between IgA anti-klebsiella and total serum IgA levels, a significant correlation between IgA anti-klebsiella and serum levels of secretory IgA was detected (r: 0.43, p = 0.003). In conclusion, some patients with AS disclosed raised levels of Klebsiella antibodies in sera and this is related to an increase of secretory IgA level. Analysis about the relationship between response to klebsiella and the presence of gut inflammation in AS patients could be of interest.

Adolescent↗

HLA and disease.

Many human diseases are associated with HLA class I, class II and class III antigens. It appears that the class III antigen disease associations can be explained by a direct defect operating at the level of either the class III gene or its gene product. The mechanism underlying class I and class II antigen disease associations is at present unknown. In this review we have considered thirty diseases which have been ranked according to their relative risk as defined by the frequency of a given HLA antigen in patient and control populations. The chronic inflammatory disorder, ankylosing spondylitis and its association with HLA B27 has been used as a model to study the HLA linked diseases. We have suggested that the disease may be caused by the Gram-negative microorganism Klebsiella which has antigenic similarity to HLA B27. It is proposed that some antibodies made against Klebsiella bind to HLA B27, thereby acting as autoantibodies leading to the pathological sequelae of chronic inflammatory arthritis. This is the crosstolerance hypothesis or molecular mimicry model and it has been compared to the receptor model. It is further suggested that the crosstolerance hypothesis can be utilised as a general theory to explain the association of other diseases with the class I and class II antigens, and offer a possible explanation for the polymorphism of HLA.

Antigen-Presenting Cells↗

Sequence similarity between HLA-DR1 and DR4 subtypes associated with rheumatoid arthritis and proteus/serratia membrane haemolysins.

Rheumatoid arthritis (RA) is found more often in subjects carrying the HLA-DR1 antigen and some subtypes of the HLA-DR4 antigen than in those without these antigens. Analysis of probes specific for HLA-DR4 has shown that amino acids encoding positions 69-74 (EQRRAA) of the beta chain indicates susceptibility to RA. A hexamer sequence of proteus haemolysin spanning residues 32-37 (ESRRAL) has been identified which resembles biochemically, and discriminates by charge, between HLA types associated with RA (DR1, Dw4, Dw14, Dw15), and those not linked with the disease (Dw10, Dw13).

Amino Acid Sequence↗

IgA antibody response to klebsiella in ankylosing spondylitis measured by immunoblotting.

IgA antibodies to Klebsiella pneumoniae var oxytoca and Proteus mirabilis were measured in 66 patients with ankylosing spondylitis (AS) and 31 with rheumatoid arthritis (RA) and in 51 healthy control subjects, using an immunoblotting technique. The number of antigenic bands to klebsiella on nitrocellulose membrane was higher in 28 patients with active AS than in 38 patients with inactive AS, 31 patients with RA, and 51 healthy control subjects; comparatively smaller increases were found against proteus. In two patients with AS the synovial fluid and the corresponding serum sample showed an identical antibody pattern. Increases in IgA antibodies to klebsiella in patients with AS confirm previous studies using other techniques.

Adult↗

Ankylosing spondylitis and HLA-B27: restriction fragment length polymorphism and sequencing of an HLA-B27 allele from a patient with ankylosing spondylitis.

Two groups of patients with ankylosing spondylitis (AS) from England and Poland were examined for restriction fragment length polymorphisms (RFLPs) associated with the disease. No preferential association was found between the 9.2 kb PvuII fragment in HLA-B27 positive patients with AS compared with HLA-B27 healthy subjects as had been previously reported. In the English group, however, a 14 kb PvuII fragment was more common in HLA-B27 positive subjects with AS than in normal controls. Also 4.6 and 3.7 kb PvuII fragments were more prevalent in subjects without AS than in the group with AS, but these results were confined to the English group. Furthermore, the sequence of an HLA-B*2705 gene isolated from a patient with AS was examined, and no significant differences were found compared with the sequence isolated from a healthy subject. There do not seem to be significant genetic differences in the coding or in the regulatory region in HLA-B27 alleles, in subjects with or without AS.

Alleles↗

Ankylosing spondylitis is caused by Klebsiella. Evidence from immunogenetic, microbiologic, and serologic studies.

Ankylosing spondylitis is a form of reactive arthritis following Klebsiella infection, usually occurring in an HLA-B27-positive individual. This conclusion is based on evidence obtained from several disciplines: immunogenetic studies show that there is molecular mimicry between HLA-B27 and Klebsiella; increased isolation of fecal Klebsiella has been reported in both Europe and North America; and finally, antibodies to Klebsiella have been demonstrated in ankylosing spondylitis patients in England and Finland. It is suggested that therapeutic trials should be set up with the aim of eliminating Klebsiella microbes, in an endeavor to test the validity of this theory.

Antigen-Antibody Reactions↗

The use of enzyme immunoassay (EIA) and radiobinding assay to investigate the cross-reactivity of Klebsiella antigens and HLA B27 in ankylosing spondylitis patients and healthy controls.

The binding of rabbit anti-Klebsiella antibodies to tissue-typed lymphocytes obtained from 30 ankylosing spondylitis (AS) patients and 54 healthy subjects has been measured by an enzyme immunoassay method. HLA B27 positive lymphocytes obtained from either AS patients (t = 3.60; p less than 0.001) or healthy subjects (t = 3.77; p less than 0.001) were found to bind Klebsiella antibodies to a significantly greater extent than non-B27 lymphocytes obtained from healthy controls. Absorption studies demonstrated that HLA B27 positive lymphocytes absorbed out significantly more anti-Klebsiella antibodies than HLA B27-negative lymphocytes (t = 6.76; p less than 0.005). These results are compatible with cross-reactivity or molecular mimicry between HLA B27 and epitopes on some Gram-negative bacteria such as Klebsiella.

Antigens, Bacterial↗

Theoretical models to explain the association of HLA-B27 with ankylosing spondylitis.

A critical examination of the five different models proposed to explain the "AS-B27" problem, has demonstrated, that two of these, the two-gene theory and the plasmid theory are no longer considered to provide satisfactory explanations of the phenomena. The remaining three theories are molecular mimicry, chemotaxis hypothesis and the receptor theory. It is difficult at this stage to decide which of these three models provides the best solution to the "AS-B27" problem, but a majority of research workers favour the receptor theory.

Animals↗

Rheumatoid arthritis and Proteus: a possible aetiological association.

The presence of specific anti-Proteus antibodies in active, rheumatoid arthritis (RA) patients, has been demonstrated by four different techniques: indirect bacterial agglutination, ELISA, Western blotting and immunofluorescence. Furthermore, anti-HLA-DR4 tissue typing sera have been shown to bind to Proteus microorganisms, thereby suggesting some molecular similarity or cross-reactivity between bacteria and HLA antigens. The concept is proposed that Proteus-reactive arthritis occurs during active phases of RA and tissue damage is mediated through immunological activity involving HLA antigens.

Antibodies, Bacterial↗

The relationship between Klebsiella infection and ankylosing spondylitis.

Ankylosing spondylitis (AS) is probably produced by repeated episodes of Klebsiella-reactive arthritis, usually in HLA-B27-positive individuals. This concept is based on immunological, microbiological and serological considerations. Immunological studies based on anti-B27 tissue typing sera and anti-B27 monoclonal antibodies indicate that HLA-B27 cross-reacts with antigens found in Klebsiella, Salmonella, Shigella and Yersinia micro-organisms. Salmonella, Shigella and Yersinia gut infections are associated with a reactive arthritis that occurs predominantly in HLA-B27-positive individuals. However, microbiological studies indicate that only Klebsiella, but not Salmonella, Shigella or Yersinia, can be isolated in faecal cultures obtained from AS patients. Furthermore, serological studies involving a number of different techniques demonstrate that only antibodies against Klebsiella, but not against Salmonella, Shigella or Yersinia, can be identified in active AS patients. The evidence is sufficiently extensive to warrant long-term studies involving Klebsiella reduction in the bowel flora of AS patients, in an attempt to reduce the severity and modify the development of the disease. It would appear that Klebsiella-reactive arthritis is the precursor stage occurring in the early and active phases of AS. Only future studies can determine whether this disease will remain a taxonomic curiosity or provide guidelines for therapeutic sequelae which will be of benefit to AS patients.

Cross Reactions↗

Klebsiella antibodies in ankylosing spondylitis and Proteus antibodies in rheumatoid arthritis.

Antibodies to Klebsiella, but not to other bacteria, have been shown to be present in patients with active ankylosing spondylitis (AS) by seven different techniques. Antibodies to Proteus, but not to E. coli or Klebsiella, have been shown to be present in patients with active rheumatoid arthritis (RA) by three different techniques. It is suggested AS and RA are forms of reactive arthritis, to Klebsiella and Proteus respectively, probably mediated by cross-reactivity to HLA antigens.

Animals↗

Antibodies to Klebsiella and Proteus microorganisms in ankylosing spondylitis and rheumatoid arthritis patients measured by ELISA.

Antibodies to Klebsiella oxytoca and Proteus mirabilis in 21 active ankylosing spondylitis (AS), 13 active rheumatoid arthritis (RA), 19 inactive RA patients and 18 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Elevated anti-Klebsiella antibodies were demonstrated in active AS patients compared to active RA (p less than 0.01), inactive RA patients (p less than 0.001) and controls (p less than 0.005). When measuring antibodies to Proteus, active RA patients showed higher levels of antibodies compared to active AS patients (p less than 0.005) and healthy controls (p less than 0.05). Further investigations are required to assess the role of Klebsiella and Proteus microorganisms in AS and RA respectively.

Adult↗

A study of antipolynucleotide antibodies, anti-Klebsiella (K30) antibodies and anti-DNA antibody idiotypes in ankylosing spondylitis.

Recent studies have indicated that both ankylosing spondylitis and the anti-DNA antibodies found in systemic lupus erythematosus may be related to Klebsiella surface antigens. In order to explore these possible relationships further, the sera of 24 patients with ankylosing spondylitis (AS), and 20 controls, have been examined for binding to a wide range of antipolynucleotide antibodies, antibodies binding to the Klebsiella pneumoniae polysaccharide K30 and two DNA antibody idiotypes designated 16/6 and 134. We report that although 21% of the AS patients had IgG ssDNA antibodies it is evident that the aetiopathogenesis of this disease is not through the mechanism of autoantibodies or the common DNA antibody idiotypes tested.

Antibodies, Antinuclear↗