Auli Toivanen

Yersinia Antigens in Synovial-Fluid Cells from Patients with Reactive Arthritis

We examined synovial-fluid cells from 15 patients with reactive arthritis after yersinia infection for the presence of yersinia antigens. Extensive bacterial cultures of the synovial fluid were negative. All the samples were studied by immunofluorescence with use of a rabbit antiserum to Yersinia enterocolitica O:3 and a monoclonal antibody to Y. enterocolitica O:3 lipopolysaccharide. Synovial-fluid cells from 41 patients with other rheumatic diseases served as controls. Synovial-fluid cells from 10 patients with reactive arthritis after yersinia infection stained positively on immunofluorescence; rabbit antiserum and the monoclonal antibody yielded similar results. In most patients the percentage of positive cells ranged from 1 to 10 percent, but in one patient nearly all the cells in the sample stained strongly. Most of the positively stained cells were polymorphonuclear leukocytes, but yersinia antigens were also found in mononuclear phagocytes. All the control samples were negative. Synovial-fluid cell deposits from nine patients were also studied by Western blotting with use of the same antibodies. The results were positive in six of the nine cell deposits from patients with reactive arthritis and in none of the 10 cell deposits from control patients with rheumatoid arthritis. We conclude that in patients with reactive arthritis after yersinia infection, microbial antigens can be found in synovial-fluid cells from the affected joints.

Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis

Synovial cells from nine patients with reactive arthritis following Salmonella enteritidis or Salmonella typhimurium infection were examined for salmonella antigens. Extensive bacterial cultures of the synovial fluid were negative. Eight synovial-fluid cell samples stained positively on immunofluorescence with rabbit antisera against heat-killed S enteritidis or S typhimurium or with monoclonal antibodies specific for the causative salmonella lipopolysaccharide (LPS). Synovial tissue from the ninth patient stained positively in the avidin-biotin-peroxidase complex method with the monoclonal antibody. Control samples (synovial-fluid cells from thirteen patients with other rheumatic diseases and synovial tissue from two) were negative. Synovial cells from eight patients and five controls were studied by western blotting with the same monoclonal antibodies. Four of the eight patients but no controls had blots indicating salmonella LPS in the synovial cells. The presence of bacterial LPS in the joint is a common and pathogenetically important feature of reactive arthritis.

Pathogenesis of Yersinia-triggered reactive arthritis: immunological, microbiological and clinical aspects.

When a patient develops reactive arthritis after Yersinia enteritis, the following conditions are often fulfilled: the patient is HLA-B27-positive; however, some B27-negative individuals develop severe arthritis and some positives do not, in the initial phase, the diarrhea is milder, the anti-Yersinia antibody response of IgG class is more vigorous and persists longer, the anti-Yersinia antibody response of IgA class is more vigorous and persists much longer, the anti-Yersinia antibodies of IgA1 and IgA2 subclass, those with J-chain and, especially, those with secretory piece are produced more vigorously, indicating local immunostimulation close to the intestinal epithelium, in the early phase, Yersinia-IgM immune complexes are found in the circulation, and the lymphocyte transformation response against not only Yersinia but also against other gram-negative enteric bacteria is weaker. When all these aspects are considered together a strong suspicion arises that the patients who are destined to develop reactive arthritis fail in their first line of defense against the invading organism when contracting a Yersinia enteritis. This may lead to persistence of the microorganism within the body, e.g., in the intestinal epithelium or in the mesenteric lymphoid tissues, maintaining a stimulus for a prolonged--apparently futile and perhaps harmful--antibody production. Finally, the initiating and decisive factor should not be forgotten: the Yersinia. Why and how it triggers the process is at present one of the enigmas of the pathogenesis of reactive arthritis.

Uptake of environmental antigens by the bursa of Fabricius

THE bursa of Fabricius of birds has an essential role as a central lymphoid organ for the differentiation of B lymphocytes1,2. In addition, the bursa harbours immunocompetent B cells3 which are capable of local antibody production. Haemolytic plaque-forming cells have been observed in the bursa after introducing sheep red blood cells (SRBC) into the bursal duct4. Furthermore, epithelial cells of the bursal follicles have been shown to transport ferritin and India ink into the intercellular spaces of the underlying lymphoid tissue when the material has been introduced into the bursal lumen5. The bursal lumen opens through the bursal duct to the most caudal of the three cloacal chambers, the proctodeum, which is of ectodermal origin6,7. The proctodeum leads to the outside through the anus and is closed externally by a strong sphincter muscle. The vent is surrounded on the outside by upper and lower anal lips. At the other end, the proctodeum opens into urodeum leading to the coprodeum and these form the cranial parts of the cloaca (Fig. 1a).

HOSPITAL OUTBREAK OF YERSINIA ENTEROCOLITICA INFECTION

Abstract An outbreak of Yersinia enterocolitica infection involving 6 members of staff in two hospital wards is described. The original source of infection was a schoolgirl, treated consecutively on both wards. Y. enterocolitica serotype 9 was isolated from this patient and from a member of the hospital staff; all infected persons had raised antibody titres against Y. enterocolitica serotype 9. Also, signs of a Y. enterocolitica infection developed in relatives of two nurses with the disease. Infection was most probably spread from person to person. These observations indicate that precautions should be taken when dealing with patients who have or are suspected of having yersiniosis.

Effect of a three month course of ciprofloxacin on the outcome of reactive arthritis

BACKGROUND Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA. OBJECTIVE To evaluate the effect of a three month course of ciprofloxacin on ReA. METHODS In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery. RESULTS Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study. CONCLUSION Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.

Bacterial antigens in synovial biopsy specimens in yersinia triggered reactive arthritis.

Non-viable structures of Yersinia enterocolitica O:3 were shown at the site of inflammation within mononuclear cells in the synovial membrane of eight out of 10 patients with yersinia triggered reactive arthritis. An avidin-biotin-peroxidase complex method, with a rabbit antiserum specific for Y enterocolitica O:3, was used to visualise yersinia structures. All 13 control samples were negative except for one with non-specific mast cell staining. The findings emphasise the significance of foreign material in the initiation of synovitis in reactive arthritis.

Synovial fluid leukocytosis in bacterial arthritis vs. reactive arthritis and rheumatoid arthritis in the adult knee.

In this comparative analysis of laboratory data, we examined the characteristics of synovial fluid leukocytosis in eighty adult patients with bacterial arthritis, reactive arthritis or rheumatoid arthritis of the knee joint. Synovial fluid leukocyte count and the percentage of polymorphonuclear cells seemed to perform well as a discriminator between bacterial infection and acute flare of the underlying disease in patients with rheumatoid arthritis. In contrast, there were no definite difference in the intensity of synovial fluid leukocytosis between patients with bacterial arthritis caused by living bacteria and patients with reactive arthritis probably caused by bacterial antigens.

Bacterial PCR in the diagnosis of joint infection

OBJECTIVES To evaluate the value of broad range bacterial PCR in the diagnosis of joint infection and to find out if there are bacteria causing arthritis which are not cultivable by the present methods. METHODS Polymerase chain reaction (PCR) with broad range bacterial primers and DNA sequencing (bacterial PCR) was used to analyse 154 synovial fluid (SF) samples from patients with different arthritic diseases. RESULTS Bacterial DNA was detected in 18 SF samples, including samples from six patients with culture proven purulent arthritis, and from three patients with possible purulent arthritis. Three samples from patients with culture confirmed purulent arthritis remained negative in bacterial PCR. CONCLUSIONS The results indicate that in the usual diagnostic laboratory setting bacterial PCR does not offer any obvious advantage over bacterial culture in the microbiological diagnosis of joint infection.

Effect of a three month course of ciprofloxacin on the late prognosis of reactive arthritis.

Background: The value of antibiotics in the treatment of reactive arthritis (ReA) is still controversial. Objectives: To analyse the long term outcome of patients with ReA, treated with a three month course of ciprofloxacin or placebo. Methods: Patients who had had ReA and had participated in a double blind, placebo controlled trial on the effectiveness of ciprofloxacin 4–7 years earlier were invited to a clinical examination. Of the 71 patients who were included in the original study, 53 agreed to visit the clinic for an examination. Twenty six of 53 patients had originally received ciprofloxacin and 27 had belonged to the placebo group. Of these, 20 in the ciprofloxacin and 25 in the placebo group were HLA-B27 positive. Results: 11/27 (41%) patients in the original placebo group had now developed chronic rheumatic disease, as compared with only 2/26 (8%) patients originally treated with ciprofloxacin (p=0.006). Two patients who originally had received placebo, none in the ciprofloxacin group had developed ankylosing spondylitis, and three patients in the original placebo group, none in the ciprofloxacin group had recurrent anterior uveitis. The same tendency was seen when several different measures were analysed. Of the patients with chronic spondyloarthropathy, 10 in the placebo and none in the ciprofloxacin group were HLA-B27 positive. Conclusion: Analysis 4–7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis.