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K Granfors

Publications and source records attributed to K Granfors.

At least 73 records · Page 4Linked to original sources

Possible confounders of the relationship between occupational swine contact and Yersinia enterocolitica 0:3 and 0:9 antibodies.

Increased risk of high Yersinia enterocolitica 0:3 and 0:9 antibody content has been previously reported in occupations with swine contact. In this study several possible confounders of this elevated risk among pig farmers and abattoir workers were considered. Only in three instances the standardized risk ratio was decreased close to unity, namely after the standardization of Y. enterocolitica 0:3 IgG antibody positivity for age among abattoir workers, after the standardization of Y. enterocolitica 0:9 IgG antibody positivity for farm butchering among pig farmers and for smoking among abattoir workers. As the decrease did not apply for both pig farmers and abattoir workers and for both 0:3 and 0:9 serotypes considered, it seems reasonable to assume that the three decreases represent products of multiple testing inherent in this kind of search of confounders rather than any true effects. In view of the present knowledge on the determinants of yersinia antibodies in populations, the crude risk ratios for elevated yersinia antibodies can be held to be reasonably unconfounded.

Abattoirs↗

A method to compare exposed populations in seroepidemiology.

In seroepidemiology when a single sample is taken from exposed and non-exposed subjects, the results of serological tests are usually reduced to a dichotomy: normal (low or no antibodies) or elevated (high or antibodies found). The choice of the cutoff point between these values has been based on various vaguely defined methods and the results depend, at least partly, on the method chosen. An alternative method is introduced here which is not based on the absolute value of a serological test but on the rank order of the values of the test. In this ordered series the risk ratio (RR) and the upper and lower confidence limits (CL) are plotted for each exposed subject as the cutoff value is moved from the highest value to the lowest one. The method is applicable in quantitative immunoassays. If a priori defined RR and confidence limit or limits are reached at any point of the plot, the data support the original hypothesis. The advantage of this alternative method is that no single cutoff value is needed.

Abattoirs↗

Salmonella specific antibodies in serum and synovial fluid in patients with reactive arthritis.

The occurrence of Salmonella specific antibodies was analysed in paired serum and synovial fluid samples from 12 patients with Salmonella triggered reactive arthritis. The antibody concentration of IgA2 subclass in synovial fluid exceeded that of serum in 8 of the 12 pairs studied, compared to 0-3 in the other immunoglobulin classes and subclasses. This finding indicates intra-articular production of IgA2 class antibodies against the triggering microbe.

Adult↗

Molecular mimicry in the pathogenesis of spondyloarthropathies. A critical appraisal of cross-reactivity between microbial antigens and HLA-B27.

We describe an amino acid homology between a virulence plasmid encoded outer membrane protein of Yersinia, YadA (previously called Yop1) and HLA-B27. This tetrapeptide is also included in the hexapeptide, earlier found to be identical between Klebsiella nitrogenase and HLA-B27. The synthetic peptide based on the HLA-B27 homologous portion of the YadA does not stimulate lymphocytes obtained from HLA-B27+ patients with Yersinia-triggered reactive arthritis or from controls. One-third of the yersiniosis patients have antibodies against the synthetic peptide. Instead of recognizing the HLA-B27 homologous portion, the antibodies are directed against the left flanking sequence of the synthetic peptide. Similar results were obtained regarding antibody response to Klebsiella nitrogenase derived synthetic peptide included in the panel of controls; the response was not restricted to patients with reactive arthritis nor was it specifically directed against the sequence shared by HLA-B27 and Klebsiella pneumoniae nitrogenase. The present results do not support the role of molecular mimicry or cross-reactive antibodies in the pathogenesis of spondyloarthropathies.

Adult↗

IgG and IgA antibody responses against porins in Yersinia-triggered reactive arthritis.

Using an enzyme immunoassay, the development and persistence of serum IgG and IgA class antibody responses against porins, a class of the major outer membrane proteins, were compared between patients who developed reactive arthritis and subjects who did not after Yersinia infection. A significant difference was seen between the two patient groups in the beginning of the disease: those with reactive arthritis had higher levels of IgG and IgA class antibodies against the porins. A similar difference in the IgA class antibodies was also seen at follow-up. This supports the hypothesis of persistence of the pathogen within the arthritic host.

Adolescent↗

Function of terminal ileum in patients with Yersinia-triggered reactive arthritis.

In order to study the function of the intestinal epithelium in the terminal ileum, the Schilling test was performed in 10 patients with Yersinia-triggered reactive arthritis, in 10 patients who had recovered from Yersinia enteritis without complications, and in five patients with rheumatoid arthritis treated with non-steroidal anti-inflammatory agents. The Schilling test indicates absorption of vitamin B12 in the terminal ileum, i.e. the area affected by Yersinia and inflamed in patients with reactive arthritis. The findings obtained demonstrate increased uptake through the epithelium in this area of the intestine in patients with Yersinia-triggered reactive arthritis. There are two possible explanations. First, Yersinia infection may have a long-term effect on the gut mucosa. Secondly, some individuals may, at the level of the terminal ileum, show enhanced absorption of vitamin B12 and/or other substances such as microbes or their components, resulting in increased susceptibility to certain infections.

Adult↗

Antibody response against 26 and 46 kilodalton released proteins of yersinia in yersinia triggered reactive arthritis.

Using an inhibition enzyme linked immunosorbent assay (ELISA) the serum antibody responses against released proteins of yersinia of molecular weights 26 and 46 kilodaltons were studied in 37 patients with and in 21 patients without reactive arthritis following yersinia infection. Although no difference was seen for the 46 kilodalton released protein, patients with yersinia triggered reactive arthritis had higher levels of antibodies against the 26 kilodalton released protein at the beginning of the disease than patients with uncomplicated yersiniosis. This may indicate an increased production of this protein in the early infection leading to poorer phagocytosis of the bacteria and thereby to the persistence of yersinia organisms within the arthritic host.

Adolescent↗

Salmonella-triggered reactive arthritis.

Clinical significance of Salmonella-triggered reactive arthritis is rising, because the frequency of Salmonella infections is increasing all over the world. In this study reports on Salmonella-triggered reactive arthritis have been reviewed. A summary of clinical, epidemiological and laboratory data, as well as triggering serotypes, is presented. Diagnostic and therapeutic aspects are also discussed.

Arthritis, Reactive↗

Antibodies against Yersinia among farmers and slaughterhouse workers.

Antibodies to immunoglobulins (Ig) M, G, and A against Yersinia enterocolitica serotypes O:3, O:5, O:8, and O:9 and Yersinia pseudotuberculosis serotypes I and III were analyzed by enzyme immunoassay of the serum samples of 161 slaughterhouse workers, 147 pig farmers, and 114 grain or berry farmers. The crude risk ratios for elevated serum antibody concentrations were calculated with the use of the grain and berry farmers as the reference population. The risk for an elevated Y enterocolitica O:3 Ig G concentration was 3.0 (95% confidence interval (95% CI) 1.3-7.1) for the pig farmers and 1.8 (95% CI 0.7-4.4) for the slaughterhouse workers and the respective risks for elevated Y enterocolitica O:9 Ig G were 2.4 (95% CI 1.1-5.5) and 1.7 (95% CI 0.7-4.0). Since these two serotypes are commonly associated with swine, the increased number of subjects with elevated antibody levels could be causally related to occupational contact with this animal.

Abattoirs↗

Do bacterial antigens cause reactive arthritis?

There are at least three common features among the microbes causing reactive arthritis: (1) they primarily cause infections on mucosal areas, (2) they are intracellularly living microorganisms, and (3) they have lipopolysaccharide as an essential structure of their outer membrane. It is obvious that during or after the acute infection microbial antigens are not properly eliminated, and they persist for long times in HLA-B27-positive persons developing ReA. Bacterial lipopolysaccharide has also been shown to enter the joints and is an important factor in the pathogenesis of ReA.

Antigens, Bacterial↗

Application of the polymerase chain reaction and immunofluorescence techniques to the detection of bacteria in Yersinia-triggered reactive arthritis.

Leukocytes in synovial fluid and peripheral blood samples from patients with Yersinia-triggered reactive arthritis were analyzed after DNA amplification using the polymerase chain reaction. The primers applied were specific for the virulence plasmid-coded 1crE genes of Yersinia enterocolitica O:3 and Yersinia pseudotuberculosis III. No Yersinia DNA was observed within the synovial fluid cells or peripheral blood cells by polymerase chain reaction techniques. However, Yersinia antigens were detected in the synovial fluid cells by immunofluorescence techniques. These results suggest that only parts of the causative agents, not the entire microbe, can enter the joint and initiate the inflammation that leads to a reactive arthritis.

Adolescent↗

Acute anterior uveitis, arthritides and enteric antigens.

One hundred and fourteen patients with acute anterior uveitis were studied for the presence of the HLA-B27 tissue type, the prevalence of spondylitis and arthritis and the occurrence of gastro-intestinal and urogenital infections or diarrhoeal illness in the history. Eighty-seven (76%) were B27+ and 27 (24%) B27-. Forty-two (48%) of the B27+ group had ankylosing spondylitis (AS); 13 (30%) of them were females. Sacroilitis (SI) with no spinal involvement was present in 21 patients (24%), 13 (61%) males and 8 (38%) females. Peripheral arthritis occurred in 6 patients. Thus, 68 (78%) of the HLA-B27+ positive patients had inflammatory spinal and/or joint disease, compared with 1 (4%) of the HLA-B27- group (p less than 0.001). The AS diagnosis was unknown previous to our examination in 31% of the males and 54% of the females, and SI was undiscovered in 61% of the males and 62% of the females. The occurrence of acute enteric infections was significantly increased in the B27+ AAU group, compared with the B27- patients and the patients reported exacerbation of AAU in connection with episodes of diarrhoea. An increased occurrence of urogenital infections was shown only in co-comparison with the males of the B-27+ AAU group. Thirty-three out of 47 AAU patients assayed by enzyme immuno-assay (EIA) for the quantification of IgM, IgA and IgG antibodies against Klebsiella pneumoniae, E coli, and Proteus mirabilis had significantly raised antibody titres against one or more of the antibodies studied, as compared to 62 healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Antibodies to arthritis-associated microbes in inflammatory joint diseases.

IgM, IgG and IgA class antibodies against Yersinia, Salmonella, Campylobacter and Borrelia were determined by enzyme-linked immunosorbent assay (ELISA) in a group of 340 unselected patients with a recent inflammatory joint disease. The control group consisted of 340 and 100 healthy blood donors using Borrelia-ELISA and other ELISAs, respectively. Of all the patients, 27.4% had increased antibody levels against at least one of the microbes tested. The prevalence of positive antibody levels was highest in Yersinia antibodies (17.9%). The corresponding figures for Salmonella, Campylobacter and Borrelia were 7.0, 6.2 and 1.8%, respectively. Patients with entero-arthritis or clinically typical reactive arthritis who had not had gastrointestinal or urogenital symptoms previously had the highest prevalence of the microbial antibodies (67.6 and 40.7%, respectively). These findings indicate that arthritis may often have a reactive etiopathogenesis without recognized gastrointestinal infection, emphasizing the importance of microbial serology in the differential diagnosis.

Antibodies, Bacterial↗

Combined use of released proteins and lipopolysaccharide in enzyme-linked immunosorbent assay for serologic screening of Yersinia infections.

An ELISA for the screening of serum antibodies to Yersinia species was developed using plasmid-encoded released proteins of Yersinia enterocolitica O:8 and lipopolysaccharide of Y. enterocolitica O:3 as a combined antigen. Of 43 sera from patients infected with one of six different Yersinia serotypes, 40 (93%) were positive in this assay. When tested using six serotype-specific ELISAs with the corresponding Yersinia bacteria as antigens, 38 (88%) were positive. This screening ELISA detects antibodies to all virulent yersiniae in one assay and offers the possibility for diagnosis of infections caused by Yersinia serotypes seen only occasionally and not usually included in the serotype-specific ELISAs. Thus, this ELISA offers a substantial advantage by saving time and money in routine laboratory work.

Adolescent↗

Salmonella-specific antibodies in reactive arthritis.

The development and persistence of Salmonella-specific serum antibodies of different immunoglobulin classes and subclasses were compared between those who developed reactive arthritis (n = 39) and those who did not (n = 58) after Salmonella infection. Antibodies against lipopolysaccharide and SDS-extract antigen were measured by ELISA. A significant difference was seen between the two patient groups after 4-14 months of follow-up; those with reactive arthritis had higher levels of Salmonella-specific IgM, IgG, and IgA class antibodies than those without arthritis. In the increased antibody response, secretory IgA, IgA1, and IgG2 classes were especially well represented. The persisting antibody response is a common feature in reactive arthritis and supports persistence of the pathogen or its components in the host. The differences observed in antibody profiles between Salmonella- and Yersinia-triggered reactive arthritides suggest certain dissimilarities (e.g., in the location of persisting microbes) in the arthritogenic process due to these two microbes.

Adolescent↗

Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix.

Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologues sequences of YadA and OmpH were observed in one-third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis-triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the HLA B27 molecule: between amino acids 70 to 78 in the variable region of alpha 1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens.

Adhesins, Bacterial↗