IgG antibodies to enterobacteria 60 kDa heat shock proteins in the sera of HLA-B27 positive ankylosing spondylitis patients

OBJECTIVE: To study the association of HLA-B27 and the IgG response to the 60 kDa HSPs of Klebsiella pneumoniae, Yersinia enterocolitica, Shigella flexneri, Escherichia coli and Salmonella typhi. METHODS: IgG against the 60 kDa HSPs of enterobacteria was determined by ELISA in the sera from 49 HLA-B27+ ankylosing spondylitis (AS) patients; 41 HLA-B27+ healthy relatives of AS patients and 101 HLA-B27-unrelated healthy individuals. RESULTS: HLA-B27+ patients and healthy individuals, showed significantly higher IgG antibody levels to the Klebsiella, Yersinia and Salmonella HSPs than HLA-B27- healthy controls. B27+ patients had a significantly higher response to E. coli HSP than the two other groups. IgG response anti-Shigella HSP was similar in the three groups. CONCLUSIONS: There is a relationship between HLA-B27 and the response to HSPs 60 from Klebsiella, Yersinia, Escherichia and Salmonella, that may be important in the initiation of AS.     

Modification of disease outcome in Salmonella-infected patients by HLA-B27

OBJECTIVE: To study whether HLA-B27 modifies the outcome of Salmonella infection in vivo. METHODS: The frequency of HLA-B27 was determined in 198 Salmonella-infected patients and 100 healthy controls by immunofluorescence and polymerase chain reaction. The excretion of Salmonella was monitored at monthly intervals. The symptoms of acute infection and possible joint involvement were evaluated using questionnaires. RESULTS: Thirty-eight of 198 Salmonella-infected patients (19.2%) and 13 of 100 healthy controls (13.0%) were HLA-B27 positive. The excretion of Salmonella did not differ significantly between HLA-B27-positive and -negative patients, or for patients with versus those without joint symptoms. As many as 35 patients (17.7%) reported Salmonella-triggered joint symptoms. Three of 14 patients (21.4%) with arthralgia, 5 of 13 patients (38.5%) with probable reactive arthritis (ReA), and 6 of 8 patients (75%) with confirmed ReA were HLA-B27 positive. The duration and severity of joint symptoms directly correlated with HLA-B27 positivity. Women reported Salmonella-induced pain and swelling of joints more frequently than men (P = 0.07 and P = 0.03, respectively). Patients with Salmonella-triggered joint symptoms reported abdominal pain and headache more frequently than patients without joint symptoms (P = 0.05 and P = 0.004, respectively). CONCLUSION: HLA-B27 did not (at least, not strongly) confer susceptibility to Salmonella infection. Salmonella excretion correlated neither with HLA-B27 positivity nor with the occurrence of joint symptoms. Joint symptoms were surprisingly common during or after Salmonella infection. HLA-B27-positive patients had a significantly increased risk of developing joint and tendon symptoms. Moreover, HLA-B27 positivity correlated with the development of more severe and prolonged joint symptoms.     

Reactivity between monoclonal anti-HLA-B27 antibodies and bacterial components: is there a consensus of findings?

Summary Studies addressing the molecular aspects of the postulated cross-reactivity between the HLA-B27 antigens and the bacteria known to precipitate arthritis (e.g., Shigella, Salmonella, Yersinia and Campylobacter) are reviewed. In conclusion, the necessity for further research into the pathogenesis of arthritis is stressed.     

Comparison of rheumatological and gastrointestinal symptoms after infection with Campylobacter jejuni/coli and enterotoxigenic Escherichia coli

OBJECTIVES: To estimate the incidence of postinfectious joint complaints after Campylobacter jejuni/coli enteritis compared with enteritis caused by enterotoxigenic E coli (ETEC). To compare gastrointestinal symptoms, antibiotic treatment, and antibody levels among patients with and without joint symptoms. METHOD: Questionnaires were sent to 210 consecutive patients with Campylobacter infection and an equal number of patients with E coli (ETEC). Blood samples for anti-Campylobacter antibodies were collected after two weeks, three months, six months, and two years. RESULTS: Twenty seven of 173 (16%) patients with Campylobacter and 10/177 (6%) with E coli (ETEC) reported joint symptoms (p=0.004). In the Campylobacter group duration of diarrhoea was a median of 13 days for patients with arthralgia and seven days for those without joint pain (p=0.0058). Patients with E coli had diarrhoea of longer duration than patients infected with Campylobacter (14 days v seven days; p=0.0005). E coli patients had fewer gastrointestinal symptoms than Campylobacter patients (p=0.0001). Fifty nine per cent of Campylobacter patients with joint pain had received antibiotic treatment because of enteritis compared with 26% with enteritis only (p=0.03). Campylobacter species and serotypes were equally distributed in both groups and there was no difference in anti-Campylobacter antibody levels between the groups. CONCLUSION: There was a significantly increased risk of developing joint symptoms after contracting Campylobacter infection compared with E coli. Campylobacter patients with joint pain had more severe gastrointestinal symptoms and longer duration of diarrhoea. Antibiotic treatment does not seem to prevent reactive joint symptoms. Levels of anti-Campylobacter antibodies were the same in both groups.     

Etiology of acute diarrhea among children in Ribeirão Preto-SP, Brazil

To study the main enteropathogens causing diarrhea in the region of Ribeir?o Preto regarding serogroups and serotypes, the feces of 1836 children under 10 years old, from both sexes, attack of acute gastroenteritis, were analysed during a period of 4 years in Adolfo Lutz Institute - Ribeir?o Preto, SP. The pathogens identified by standard methods were the following: Escherichia coli, Salmonella spp., Shigella spp., Campylobacter spp., Yersinia spp., and Cryptosporidium spp. Positive samples were 22.8% (419) with 1.7% association of pathogens. Larger isolates were mainly from children 0 to 11 months old. Enteropathogenic E. coli (EPEC) was most frequent (8.7%) with predominance of serogroup O119 (40.2%), followed by Shigella (6.2%), 63.6% of which S. sonnei.     

Invasion of Salmonella into human intestinal epithelial cells is modulated by HLA-B27

OBJECTIVE: To investigate the influence of the major histocompatibility complex (MHC) class I molecule HLA-B27 on (i) the invasion of Salmonella and Yersinia into human intestinal epithelial cells, (ii) the survival of intracellular Salmonella in these cells, and (iii) the production of certain inflammatory cytokines by the cells after Salmonella infection. METHODS: The human intestinal epithelial cell line Henle-407 was transfected with HLA-B27 DNA. These cells and HLA-B27-negative control cells were infected with Salmonella or Yersinia, and viable intracellular bacteria were determined as colony-forming units. Cytokine production was assayed with ELISA. RESULTS: Salmonella invaded HLA-B27-positive Henle cells in higher numbers than HLA-B27-negative control cells. However, HLA-B27 did not affect the invasion of Yersinia or the survival of the intracellular bacteria in these intestinal epithelial cells. Salmonella infection induced production of interleukin-8 (IL-8), IL-6 and monocyte chemotactic protein 1 (MCP-1) by Henle cells that was not affected by HLA-B27 in a specific way. CONCLUSIONS: These findings suggest that HLA-B27 enhances the invasion of Salmonella into intestinal epithelial cells. The interaction between bacteria and intestinal epithelial cells plays an important role during the early phases of ReA. HLA-B27-linked modulation of Salmonella invasion may lead to an increased load of Salmonella in intestinal tissue and thus increased susceptibility to reactive arthritis.     

Diarrhea associated with rotaviruses, enterotoxigenic Escherichia coli, Campylobacter, and other agents in Costa Rican children, 1976-1981

Rotaviruses, enterotoxigenic Escherichia coli, Salmonella, Shigella, and parasites were investigated in outpatient diarrheic children, and in hospitalized diarrheic and non-diarrheic children, between January 1976 and June 1979. In outpatient cases studied within 4 days of onset of symptoms, rotaviruses were the most common agents (45.3%); E. coli heat-stable enterotoxin ranked second (13.4%); Shigella was third (8.1%); Salmonella was fourth (7.3%). In 63.2%, one or more enteric agents were detected. In hospitalized non-diarrheic children, asymptomatic shedding of pathogens was rarely observed. A later survey of outpatient diarrheic children revealed Campylobacter fetus jejuni in 8%. In 5.5 years of observation rotaviruses were endemic with excess frequency in the dry and cooler months of December and January. The excess occurrence of bacterial pathogens did not coincide with that of rotaviruses.     

Human lymphocyte response to selected infectious agents in Reiter's syndrome and ankylosing spondylitis

Summary Reiter's syndrome (RS) and idiopathic ankylosing spondylitis (AS) have been associated with certain infections and the histocompatibility antigen HLA-B27. The proliferative responses of peripheral mononuclear cell preparations from 18 patients with RS, 6 with AS, and 22 unaffected subjects were studied toward Shigella flexneri, Salmonella typhimurium, Yersinia enterocolitica, Klebsiella pneumoniae, and Chlamydia trachomatis. Although RS, AS, and HLA-B27-positive normal subjects had generally higher mean responses than HLA-B27-negative controls, no significant differences were demonstrated. Using a chromium release assay, the cytotoxicity of an HLA-B27 antiserum was not altered by preincubation of lymphocytes with these organisms for several individual subjects in each study group.     

CT evaluation of infectious colitis]

Computed tomography (CT) is useful for evaluating the diagnosis of gastrointestinal disease, such as infectious colitis, in patients with severe pain and bloody diarrhea. During the 7 years between November 1993 and October 2000, 34 patients with infectious colitis (18 male, 16 female; mean age 42 +/- 19 yrs), received emergency CT and colonoscopy because of severe abdominal pain and dysentery. The following organisms were isolated: pathogenic Escherichia coli (12), 6 of which were O157:H7 (O-157), Salmonella species (11), Campylobacter species (5), Vibrio parahaemolyticus (3), Yersinia enterocolotica (2) and Shigella species (1). Thickening of the intestinal wall greater than 10 mm was seen in the ascending colon in the 6 cases with E. coli O 157, in 5/11 cases with Salmonella, 4/5 with Campylobacter and 1/6 with non-O157 pathogenic E. Coli. Marked intestinal wall thickening, greater than 20 mm, was seen in the ascending colon of the 4 of the patients with an O-157 infection. In all patients with O-157 colitis, slight ascites was noted in the pelvic space. In additions, ascites was also seen in 3/13 patients with Salmonella and 1/5 patients with Campylobacter colitis. The CT findings, in the patients with infectious colitis, are non-specific but knowledge and recognition of the findings will help in patient evaluation and proper treatment.     

Microbial factors in spondyloarthropathies: insights from population studies

Infections and genetics play a role in the development of reactive arthritis. The clinical manifestations and severity of the features depend on the triggering infections and the epidemiologic setting. Reports from hospital-based series show the lowest frequency of reactive arthritis, but often, patients have severe arthritis associated with a high frequency of HLA-B27. At the population level, reactive arthritis occur in 7 to 15% of the infected subjects. The disease is usually mild, affects small joints, can be polyarticular, often rapidly disappears, and has a low association with HLA-B27. There also seems to be a change in the spectrum of triggering infections. Reports of Yersinia arthritis are less common, whereas arthritis in association with Campylobacter or Salmonella infections seems to be increasing. The role of early antimicrobial chemotherapy for the prevention of reactive arthritis needs to be studied.     

Acute diarrhea due to enteropathogenic bacteria in patients at hospitals in Tehran

During a study examining causes of diarrhea from May 2004 to May 2005, 808 stool specimens were collected from patients with acute diarrhea in Tehran. Fecal samples were cultured and identified according to the standard biochemical methods. Molecular identification of enteropathogens was carried out by amplification of their virulence genes by polymerase chain reaction. A total of 369 (45.6%) bacterial pathogens were recovered from 808 patients as follows: Shigella spp., 155 (45.6%); diarrheagenic Escherichia coli 143 (38.8%); Salmonella spp., 51 (13.8%); and Campylobacter spp., 20 (5.4%). Most of the diarrheagenic E. coli were Shiga toxin-producing E. coli, with 64 (44.7%) isolates, followed by 47 (32.9%) enterotoxigenic E. coli isolates; among Shigella spp. isolates, 69 (44.5%) Shigella flexneri were predominant. The molecular diagnosis of enteropathogens yielded a more accurate characterization of the prevalence of diarrhea-causing bacterial strains in Iran. The present study revealed a high prevalence of Shigella and diarrheagenic E. coli as the predominant causes of bacterial diarrhea in this region of the world. These two types of bacteria should therefore be considered when designing preventive strategies for people living in Iran.     

HLA-B27-Negative Arthritis Related to Campylobacter Jejuni Enteritis in Three Children and Two Adults

ABSTRACT. Five out of 37 patients with proven Campylobacter jejuni enteritis developed arthritis. Two adult patients presented with classical Reiter's syndrome. One of the three children had reactive arthritis, and clinical suspicion of septic arthritis could not be confirmed in two. The acute synovitis subsided usually without treatment in all patients within 3–7 days, while arthralgia persisted longer in 4 patients. HLA-B27 was not present in the 5 patients with arthritis, but was found in 4 others. In Northern Norway, Campylobacter fetus ssp. jejuni is more frequently isolated from stool specimens than Salmonella, Shigella and Yersinia enterocolitica. Synovial fluid should be cultured following Campylobacter jejuni enteritis in arthritis patients.     

Clinical trial of T-3262 on acute enteritis. Japan Research Committee of T-3262, Research Group for Acute Infectious Enteritis

For the purpose of evaluation of clinical efficacy, safety and usefulness on acute infectious enteritis (bacillary dysentery, and enteritis caused by Salmonella spp., Campylobacter spp., enteropathogenic E. coli, and so on), T-3262, a newly developed pyridone-carboxylic acid derivative, was administered to a total of 136 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). The daily dose of 450 mg of T-3262 was administered orally three times after meals for 5 days, with the exception of 7 day administration against Salmonella enteritis. A total of 89 cases were evaluated; 23 with Shigella spp., 30 with Salmonella spp., 15 with Campylobacter spp., 6 with enteropathogenic E. coli, and 15 cases with the other pathogens or pathogen-negative. The efficacy on clinical symptoms judging from duration of fever, and duration of diarrhea and abnormal stool character was 100% in all the enteritis except enteropathogenic E. coli enteritis, in which it was 50% (n = 2). Concerning bacteriological response, elimination of the causative organisms from the feces was 100% in Shigella spp. (n = 19), Salmonella spp. (n = 30), and enteropathogenic E. coli (n = 6), although 64.3% in Campylobacter spp. (n = 14). As an adverse effect, epigastric discomfort was observed in one (0.8%) of 130 cases. Deteriorations in laboratory findings were seen in five (6.2%) of 81 cases, consisting of two with elevated GOT and GPT, two with elevated GPT, and one with increased eosinophils count, although they were all slight in degree. MICs of T-3262 which inhibited 90% of the isolates of Shigella spp, Salmonella spp., and Campylobacter spp., were 0.025, 0.05, and 0.78 microgram/ml, respectively. These values were lowest among the quinolone derivatives tested, except that the MIC90 against Campylobacter spp. was the same as that of ofloxacin.     

Anti-HLA-B27 antibodies in sera from patients with gram-negative bacterial infections

Several forms of seronegative polyarthritis are strongly associated with HLA-B27, and a number of microorganisms have been implicated in the etiology of these diseases. To explain the association between HLA-B27 and arthritis initiated by infection with these organisms, it has been proposed that there is immunologic cross-reactivity between the B27 molecule and 1 or more microbial antigens, and that this cross-reactivity leads to tolerance to such infection and/or to the production of anti-HLA-B27 cross-reactive antibodies. Such cross-reactive antibodies were detected in the sera of only 2 of 63 patients recently infected with Shigella flexneri, Campylobacter jejuni, or Yersinia enterocolitica who had highly significant antibody levels against the infecting bacterial species. Most striking was the absence of anti-HLA-B27 antibody in the serum of 16 of 17 patients who developed reactive arthritis following Yersinia infection.     

Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis

OBJECTIVE: Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients. METHODS: Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor (RF)-positive RA, 16% RF-negative RA, 17% a spondyloarthropathy and 37% undifferentiated arthritis. Serum antibodies to P. mirabilis, Escherichia coli and other potentially arthritogenic organisms (Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia and parvovirus B19) and for antibodies specific for immunoglobulin (Ig) G damaged with advanced glycation end-products (anti-IgG-AGE) were measured. RESULTS: IgM and IgA anti-Proteus antibodies were significantly higher in patients with RF-positive RA compared with all other patient groups (P < 0.0005 and P < 0.005). Anti-P. mirabilis IgG, and IgG, IgA, and IgM antibodies to other potentially arthritogenic pathogens did not differ in the patient groups. IgM antibodies to E. coli were elevated in RF-positive RA patients. Anti-P. mirabilis IgM and IgA results were not explained by false-positive reactions, because after absorption of RF there was no decrease in antibodies to Proteus in 10 of 12 patients. Proteus and E. coli antibodies were highest in patients positive for both RF and anti-IgG-AGE antibodies (P<0.001). Patients with erosions tended to have higher IgA anti-Proteus titres, but no association with the shared HLA epitope or treatment was detected. CONCLUSION: Anti-P. mirabilis IgM and IgA and anti-E. coli IgM antibody elevations are associated with early seropositive RA and the presence of anti-IgG-AGE antibodies. The role that P. mirabilis or E. coli plays in early RF-positive RA requires further investigation.     

Ten-year follow-up study of patients with Yersinia arthritis

Eighty-five patients with acute Yersinia arthritis were seen in followup for a mean of 10 years. During that time, peripheral joint symptoms occurred frequently (51.8%), but these symptoms were mild (45.9%). Development of a new reactive arthritis (4.7%) or chronic arthritis (2.4%) was uncommon. One-third of the patients experienced low back pain, and one-third of the patients had radiologic evidence of sacroiliitis. The presence of sacroiliitis was more frequent in patients with low back pain (46.7%) than in those who did not have symptoms (21.2%). More patients with HLA-B27 had low back pain and sacroiliitis, but there was no association of this genetic factor with the residual symptoms in peripheral joints.     

Arthritis associated with enteric infection

Reactive arthritis is classically seen following infection with enteric pathogens such as Yersinia, Salmonella, Campylobacter and Shigella. Inflammatory arthritis has also been described following other enteric infection with organisms such as Clostridium difficile, Brucella and Giardia. Furthermore, arthritis is seen in Whipple's disease, caused by the actinomycete Tropheryma whippelii. This chapter reviews the current understanding of these conditions (with the exception of Brucella, which is discussed in a subsequent chapter). The epidemiology is reviewed, and the contribution of both host and organism to the aetiology and pathogenesis is discussed with particular discussion of the role of HLA-B27 in host susceptibility. Recent work exploring evidence for traffic of pathogenic organisms to the joint is highlighted. A practical approach to the diagnosis and management of the condition is then formulated based, where possible, on clinical trial evidence.     

Bacterial enteric pathogens in children with acute dysentery in Thailand: increasing importance of quinolone-resistant Campylobacter

Current data on pathogen prevalence and drug resistance patterns are important for treatment and vaccine-development strategies. An etiologic study of acute bacterial dysentery was conducted in children up to 12 years of age in 2 major hospitals in and around Bangkok. Stool samples or rectal swabs and clinical data were collected. Standard microbiological methods were used to detect Salmonella, Shigella, Campylobacter, Vibrio, Aeromonas and Plesiomonas. Pathogenic E. coli (ETEC, EIEC, STEC) was identified by digoxigenin-labeled probes. A total of 623 cases were enrolled: median age 11.0 months (range 1 month-12 years). At least one bacterial pathogen was isolated in 55% of cases. Campylobacter was the most common pathogen found (28%), whereas Salmonella, Shigella and ETEC were isolated from 18%, 9% and 6% respectively. EIEC, Vibrio and Plesiomonas were isolated from <1% and no STEC was detected. C. jejuni serotypes 36, 4 and 11 were the most common. The mean age of cases with Campylobacter was significantly lower than with Shigella (17.9 vs 52.8 months, p<0.001). Clinical presentations of Campylobacter and Shigella infections were compared: fever (28% vs 37%), abdominal colic (62% vs 80%, p<0.05), vomiting (38% vs 70%, p<0.001) and bloody stools (52% vs 48%). The Campylobacter isolates (80% C. jejuni, 20% C. coli) were 90% resistant to ciprofloxacin but sensitive to macrolides. All the Shigella isolates (70% S. sonnei) were sensitive to quinolones. Our study illustrates the increasing importance of quinolone-resistant Campylobacter and the decline of Shigella in the etiology of dysentery in Thailand. The clinical presentation of campylobacteriosis is similar to that of shigellosis, except that the patients may be younger and there may be less association with colic and vomiting; having fecal leukocytes will be >10/HPF. The use of macrolide antibiotics rather than quinolones would be reasonable in children <24 months of age; fluoroquinolones will be ineffective in at least half of culture-positive cases.     

Acute community-acquired diarrhea requiring hospital admission in Swiss children.

In order to ascertain the prevalence of agents that cause childhood diarrheal illness, stool specimens of 312 consecutive children with community-acquired diarrhea requiring admission were evaluated. Pathogens were detected in 166 (53%) of the 312 children (>/=2 pathogens in 28 children): Rotavirus (n=75), Salmonella spp. (n=37), Campylobacter spp. (n=24), Shigella spp. (n=5), Giardia spp. (n=4), Yersinia spp. (n=2), Aeromonas spp. (n=15), Cryptosporidium (n=15), enteropathogenic Escherichia coli (n=13), enterotoxigenic E. coli (n=7), and enterohemorrhagic E. coli (n=5). In conclusion, acute childhood diarrheal illness pathogens, such as Aeromonas, Cryptosporidium, and diarrheagenic E. coli, account for a large proportion of patients with a microbiologically positive stool specimen.