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K Granfors

Publications and source records attributed to K Granfors.

At least 37 records · Page 2Linked to original sources
PubMed1999

Detection of Salmonella infantis in synovial fluid cells of a patient with reactive arthritis.

We investigated a patient with Salmonella infantis triggered reactive arthritis (ReA) for a possible occurrence of S. infantis-specific antigens and DNA in the synovial fluid (SF) cells. S. infantis-specific antigens were abundantly observed by immunofluorescence in SF cells of the patient during acute joint inflammation. Salmonella-specific DNA was detected by Southern blotting of the amplified polymerase chain reaction product once, but the result could not be repeated. It seems that if bacterial DNA exists in inflamed joints in Salmonella triggered ReA, its amount is extremely low. This is the first report of intraarticular S. infantis antigens and potentially of Salmonella DNA in Salmonella triggered ReA.

Adolescent↗
PubMed1998

Persistence of Yersinia antigens in peripheral blood cells from patients with Yersinia enterocolitica O:3 infection with or without reactive arthritis.

OBJECTIVE: To assess the persistence of bacterial antigens in peripheral blood cells from patients with Yersinia enterocolitica O:3-triggered reactive arthritis (ReA). METHODS: Peripheral blood samples were obtained from 20 patients with Y. enterocolitica O:3 infection (11 with ReA and 9 without). These samples were studied by immunochemical techniques for the presence of Yersinia antigens at the beginning of infection and up to 4 years thereafter. Synovial fluid samples from 6 of the 11 ReA patients were also studied. RESULTS: The Yersinia antigens lipopolysaccharide and heat-shock protein (HSP) were detected in peripheral blood mononuclear cells and polymorphonuclear phagocytes from all patients studied at the early phase of the disease. They were also found in the synovial fluid cells of patients with Yersinia-triggered ReA. At 4 years after the onset of infection, these bacterial antigens were still detected in the peripheral blood cells of most of the ReA patients studied. CONCLUSION: This study has, for the first time, directly demonstrated that bacterial antigens persist for a long time in patients who develop ReA after Y. enterocolitica O:3 infection. The finding of bacterial HSP in synovial fluid cells could provide a link to the pathogenesis of ReA, since T cell responses of synovial cells have been shown to be directed against that structure. A close similarity between the bacterial and host HSP might contribute to the development of the relatively common, chronic form of this complication.

Antibodies, Bacterial↗
PubMed1998

Increased synovial endothelium binding and transendothelial migration of mononuclear cells during Salmonella infection.

OBJECTIVE: To investigate the adhesion and extravasation capacity of peripheral blood mononuclear cells (PBMC) and the transport of bacterial antigens within these cells during Salmonella infection. METHODS: Thirteen patients who were part of 2 outbreaks of Salmonella enteritidis infection were included in this study. The capacity of PBMC from these patients to bind to vascular endothelium in inflamed synovium was tested using a Stamper-Woodruff-type frozen-section assay. The same cells were studied for the presence of Salmonella antigens by immunofluorescence staining. The transendothelial migration of mononuclear cells containing Salmonella or its components through unstimulated endothelial cell layer was quantified. RESULTS: The capacity of PBMC to adhere to synovial vessels was significantly increased during Salmonella infection (P=0.0003). Monocytes had a transiently high adhesive state between 2 and 5 weeks after the patients had eaten the contaminated food. The cells containing Salmonella antigens were concentrated in the transmigrated population. CONCLUSION: During acute Salmonella infection the increased binding of PBMC to vascular endothelium in inflamed synovium and enhanced transmigration of PBMC containing Salmonella may be the key factors leading to transport of bacterial antigens through the endothelial barrier and initiation of arthritis in susceptible individuals.

Adult↗
PubMed1998

Reactive arthritis following an outbreak of Salmonella Bovismorbificans infection.

A large, single-source Salmonella outbreak caused by a rare serovar Bovismorbificans (6,8:r:1,5) occurred in southern Finland in 1994. The origin of the outbreak was sprouted alfalfa seeds. A questionnaire was mailed to all 210 subjects with positive stool culture. Ninety-one percent (191/210) returned the questionnaire. One hundred and fifty-three (80%) were adults. One hundred and fifty-nine out of one hundred and ninety-one (83%) reported diarrhoea, 109 (57%) fever, 104 (54%) abdominal pains, 83 (43%) fatigue, 66 (35%) articular symptoms and 20 (10%) had no symptoms. The median duration of diarrhoea was 5 days (range 1-35), that of other symptoms 4 days (range 1-30). Those reporting articular symptoms were examined (51 patients) or contacted by telephone (13 patients). Twelve percent (22/191) fulfilled the criteria for reactive arthritis (ReA). The difference in the incidence of ReA between children and adults was not significant (8%, vs. 12%). The median onset of joint symptoms was 8.5 days; symptoms were oligoarticular in 14 (67%) and polyarticular in four (19%) patients. Mostly ReA was mild, but in four patients (18%) the joint symptoms lasted for more than 4 months. Ten (45%) ReA patients had HLA-B27 tissue type. The duration and severity of ReA did not differ between HLA-B27 positive and negative patients. Fourteen (64%) ReA patients had received fluoroquinolone treatment before reactive joint or tendon symptoms manifested, but this treatment did not prevent ReA symptoms.

Adult↗
PubMed1998

Infectious agents as triggers of reactive arthritis.

Reactive arthritis was originally defined as a sterile joint inflammation after infection elsewhere in the body, but this view has been challenged in the past decade since different antigens and DNA and RNA of various triggering microbes have been shown to exist at the sites of inflammation in the joints. It has been suggested that microbial antigens, or intact pathogens, are important for the pathogenesis of reactive arthritis, at least in the early phase of the disease, but the exact mechanism of how the pathogens contribute to the development of this usually self-limiting polyarthritis has not been discovered. This article reviews the theories on the role of infectious agents as triggers of reactive arthritis.

Animals↗
PubMed1998

IgA class serum antibodies against three different Klebsiella serotypes in ankylosing spondylitis.

OBJECTIVE: To investigate the possible predominance of certain Klebsiella pneumoniae capsular types in the pathogenesis of ankylosing spondylitis (AS). METHODS: The prevalence of IgA class antibodies against three different K. pneumoniae strains (with capsular types 21, 30 and 43) was studied in the sera of 177 patients with AS and of 100 healthy blood donors using an enzyme-linked immunosorbent assay. RESULTS: The median Klebsiella-specific antibody levels were always higher in patients than in controls regardless of the serotype used as antigen. When the prevalence of increased antibody levels was compared between the groups, it was highest against the strain with capsular type 30, whereas against strains 21 and 43 it was similar among patients and controls. CONCLUSIONS: A broad range of Klebsiella serotypes may be involved in the pathogenesis of AS. Thus, it is important to take the different Klebsiella serotypes into particular account in these studies.

Adult↗
PubMed1997

Induction of alternative splicing of HLA-B27 by bacterial invasion.

OBJECTIVE: Alternative splicing of certain class I major histocompatibility complex pre-messenger RNA (pre-mRNA) is known to lead to generation of a cell-free soluble protein analog. This study was undertaken to examine whether this process occurs with HLA-B27, whether the process is modified by arthritis-causing bacteria, and whether the assembly of the soluble molecules follows the same pathway as the integral parent molecules. METHODS: Alternative splicing of pre-mRNA was analyzed by reverse transcriptase-polymerase chain reaction, and assembly of soluble HLA-B27 by immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. RESULTS: There was alternative splicing of the pre-mRNA of HLA-B27. The process could be amplified by invasion with Salmonella or Yersinia bacteria. The soluble HLA-B27 was assembled in a pathway similar to that of the parent molecule. CONCLUSION: The association between arthritis-causing bacteria and HLA-B27 positive cells is a complex event. Soluble HLA-B27 is a potential key player.

Alternative Splicing↗
PubMed1997

HLA-B27 modulates intracellular survival of Salmonella enteritidis in human monocytic cells.

Human major histocompatibility complex class I allele HLA-B27 is associated with a group of diseases called spondyloarthropathies. In reactive arthritis (ReA), the disease is triggered by certain infections, e.g. gastroenteritis caused by Salmonella. The host/microbe interaction is abnormal in susceptible individuals leading to inefficient elimination of arthritis-triggering bacteria, fragments of them, or both, after the initial infection. Using transfected human monocytic U937 cell lines, we demonstrate that the expression of the HLA-B27 antigen does not influence the uptake of S. enteritidis into U937 cells in vitro. Interestingly, HLA-B27 remarkably impairs the elimination of S. enteritidis within the HLA-B27 transfected U937 cells. The impaired elimination of ReA-triggering microbes by HLA-B27+ monocytes may offer an explanation for the persistence of ReA-triggering microbes in susceptible HLA-B27+ individuals. This modulation of the host/microbe interaction by HLA-B27 may have an important role in the pathogenesis of ReA.

Cell Count↗
PubMed1997

High frequency of Yersinia antibodies in healthy populations in Finland and Germany.

Sera from 94 healthy Finnish and 100 healthy German blood donors were studied for Yersinia enterocolitica antibodies by two different techniques, enzyme immunoassay and immunoblotting, to compare the frequency of Yersinia infections in Finnish and German populations. The prevalence of Yersinia antibodies in Finland (19% and 31% by enzyme immunoassay and immunoblotting, respectively) and in Germany (33%, 43%) is relatively high and may indicate many subclinical Yersinia infections in healthy populations. Postinfectious complications, such as reactive arthritis, may follow also such subclinical infection; sensitive serological tests are important in their diagnosis.

Adolescent↗
PubMed1997

IgM, IgG and IgA class enterobacterial antibodies in serum and synovial fluid in patients with ankylosing spondylitis and rheumatoid arthritis.

IgM, IgG and IgA class antibodies against three Klebsiella pneumoniae capsular types, Escherichia coli and Proteus mirabilis, as well as total immunoglobulin concentrations, were measured by enzyme immunoassay and radial immunodiffusion technique, respectively, in paired serum and synovial fluid samples from eight patients with ankylosing spondylitis and 10 with rheumatoid arthritis. No clear evidence for intra-articular antibody production against any of the studied microbes was found.

Adult↗
PubMed1997

False-negative serological HLA-B27 typing results may be due to altered antigenic epitopes and can be detected by polymerase chain reaction.

Serological typing with the microlymphocytotoxicity test (MLCT) and flow cytometry (FC) using HLA-B27 antisera is commonly used for the determination of HLA-B27. However, in some patients tested more than once, negative results have turned out to be positive at following investigations. We retested by polymerase chain reaction (PCR) samples from 20 randomly selected patients with reactive arthritis or Reiter's syndrome who had now been followed for 20 yr. Ten of the patients were originally tested to be HLA-B27 positive and 10 HLA-B27 negative by the MLCT. All 10 serologically HLA-B27 positive individuals were also positive in the PCR. However, 2/10 patients interpreted as being HLA-B27 negative were positive by PCR. At this time, the same two patients were also positive in the routine MLCT and FC using four different monoclonal antibodies against HLA-B27. PCR is superior to serological techniques to determine HLA-B27 positivity unequivocally, since it is based on the detection of HLA-B27 gene sequences.

Aged↗
PubMed1997

HLA-B27 modulates the survival of Salmonella enteritidis in transfected L cells, possibly by impaired nitric oxide production.

Reactive arthritis is triggered by certain microbes that cause primary infections mainly on the gastrointestinal or urogenital mucosa. The disease is strongly associated with HLA-B27. Long persistence of causative microbes or their structures in the body has been thought to have an important role in the pathogenesis of reactive arthritis. This suggests that the elimination of the microbes causing reactive arthritis is ineffective or disturbed in HLA-B27-positive individuals developing this complication. We examined the role of the HLA-B27 antigen in microbe-host interaction in vitro by monitoring the invasion and intracellular survival of Salmonella enteritidis in mouse fibroblasts transfected with HLA-B27, HLA-B7, or beta2-microglobulin only. S. enteritidis invaded into all the three transfectants with the same efficiency. However, at 6 and 10 days after incubation, there were more living intracellular Salmonella organisms in HLA-B27 transfectants than in the other transfected cell lines (P < 0.05), suggesting that the bactericidal effect is impaired in these cells. Impaired NO production in HLA-B27-transfected cells was indicated as a possible mechanism, since the amount of nitrite in the supernatants of the Salmonella-infected HLA-B27-transfected cells was smaller than that in the supernatants of the Salmonella-infected HLA-B7- or beta2-microglobulin-transfected cells (P < 0.001). The inhibition of NO synthesis by N-monomethyl-L-arginine resulted in impaired elimination of Salmonella also in HLA-B7and beta2-microglobulin-transfected cells. The inverse correlation between intracellular survival of Salmonella and the amount of nitrite detected in culture supernatants supports the hypothesis that the L-arginine-dependent NO pathway plays an important role in the murine fibroblast response against Salmonella. We suggest that a major histocompatibility complex class I antigen, HLA-B27, may contribute to the intracellular persistence of Salmonella by a mechanism which involves the NO pathway.

Animals↗
PubMed1997

Yersinia enterocolitica serotype O:3 alters the expression of serologic HLA-B27 epitopes on human monocytes.

The expression of serologic HLA-B27 epitopes on leukocytes of patients with reactive arthritis or ankylosing spondylitis has been shown to be modified in the course of the disease. The purpose of this work was to study whether phagocytosis of arthritis-triggering microbes in vitro alters the expression of HLA-B27 molecules on human antigen-presenting cells and to characterize the underlying mechanisms. Human monocytes and HLA-B27- or HLA-A2-transfected human U-937 cells were exposed to Yersinia enterocolitica serotype O:3. The expression of different epitopes of HLA-B27 was monitored by using immunofluorescence, and their synthesis was determined by quantitative immunoprecipitation. Our results show that phagocytosis of Y. enterocolitica serotype O:3 changed the expression of serological HLA-B27 epitopes. This was due to the reduced synthesis of HLA-B27 molecules. The expression of especially the epitopes which depend on the presence of peptides in the antigen-binding groove was changed. The expression of the ME1 epitope, which has been shown to be important for T-cell recognition in patients with reactive arthritis, was decreased. Down-regulation of epitopes important for the T-cell recognition may impair the elimination of arthritis-triggering microbes and lead to persistent infection. In addition, Y. enterocolitica serotype O:3 seemed to alter the repertoire of peptides presented by the HLA-B27 molecules on human monocytes. This may have a role in the pathogenesis of reactive arthritis via an autoimmune mechanism.

Brefeldin A↗
PubMed1997

Association of gut inflammation with increased serum IgA class Klebsiella antibody concentrations in patients with axial ankylosing spondylitis (AS): implication for different aetiopathogenetic mechanisms for axial and peripheral AS?

OBJECTIVES: A role for Klebsiella pneumoniae in ankylosing spondylitis (AS) has been suggested because faecal carriage of Klebsiella and serum Klebsiella specific antibodies may be increased in this disease. This study has extended the earlier findings by comparing Klebsiella specific serum IgA class antibodies with inflammatory changes in the gut. METHODS: IgA antibodies to K pneumoniae, Escherichia coli, and Proteus mirabilis in serum samples of 25 patients with AS, of eight control patients, and of 100 healthy blood donors were measured by enzyme immunoassay. Gut inflammation of the patients was studied by ileocolonoscopy. RESULTS: Increased IgA antibody concentrations to K pneumoniae associated with gut inflammation in patients with axial form of AS. Such association was not seen in patients with peripheral form of AS. CONCLUSIONS: These findings may provide further evidence for the role of K pneumoniae in the pathogenesis of AS. However, at least some of the patients with axial AS without gut inflammation, as well as patients with peripheral AS did not have increased K pneumoniae antibody concentrations, which may be regarded as evidence against the direct role of K pneumoniae in the pathogenesis. The aetiopathogenetic mechanisms in the axial and peripheral form of AS may be different.

Antibodies, Bacterial↗
PubMed1997

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.

Adult↗
PubMed1997

Host-microbe interaction in HLA-B27-associated diseases.

The mechanisms leading to the development of HLA-B27-associated diseases, spondyloarthropathies, are unknown. One of them, reactive arthritis, is clearly caused by an infection, and joint inflammation develops soon after or during an infection elsewhere in the body. In other forms of spondyloarthropathies, such as ankylosing spondylitis, association with infection is suggested but it is not as clear. Pathogenetic mechanisms of reactive arthritis are a focus of great interest as causative infections and strong genetic association are known. How HLA-B27 determines the appearance of joint complications after certain infections is not clear. Several theories have been proposed to explain the association, and they usually include the idea that interaction between microbe and host is abnormal and inefficient in HLA-B27-positive subjects in whom reactive arthritis develops.

Arthritis, Infectious↗