YERSINIA ENTEROCOLITICA ANTIBODIES
Summary
A parent of the child with highly elevated Yersinia enterocolitica (YE)
antibodies (as determined by Immuno-Sci-Lab colitis/ibd panel) and with Yersinia
not mentioned in his Great Smokies intestinal microbiology panel wondered about
the possibility that the child's anti-YE titers might have been due to cross-
reactivity with sequences from other pathogens or perhaps even certain self-
antigens (a process rooted in molecular similarities called molecular mimicry).
A Medline search (for mimicry and cross-reactivity regarding YE) generated
citations suggesting that the specificity of the lab's assay ought be verified
and that the child may have "mild" thyroid effects based upon bacterial
interaction with TSH and/or upon anti-YE antibodies that may be binding to a
significant proportion of the child's thyrotropin receptors.
Importantly, epidemiological studies reveal that a number of adults are
likely to be YE carriers, and even among children, seemingly asymptomatic YE
carrier-status has been documented. Combined, these epidemiologic findings
suggest that some children may have chronic YE -- a status that can include
impaired monocyte function, which itself would constitute an ongoing immune
impairment.
YE-monocyte citations are presented on
http://www.jorsm.com/~binstock/yersin.htm
Considerations from YE/cross-reactivity readings
Herewith is an initial summary from YE/cross-reactivity literature as presented
in Medline; individuals wanting to read the abstracts and citations may do so
by downloading or printing http://www.jorsm.com/~binstock/yersin-2.htm
[a-1,2] Yersinia enterocolitica has some cross-reactivity with E. coli 0157,
which suggests the lab (ImmunoSciences Lab, Inc) would have to describe the
specificity of their Yersinia enterocolitica reagent, especially for a child
known to have hEc.
[a-3] Keeping in mind that the narrow specificity of assays does not reflect
the wide range of antibodies actually generated by a specific pathogen, we note
that one study reported that E. coli 0157 antibodies did not cross react with
Y.e; but in reverse, YE antibodies cross-reacted with E. coli.
{This is a 1991 study. Again, ImmunoSciLab personnel can
determine the accuracy of the YE assay the lab offers in
1999.}
[b] Brucella abortus is a remote possibility: "Serological cross-reactivity
between Brucella abortus and yersinia enterocolitica 0:9:"
[c] Graves disease linked with Coxsackie and HLA-DR3, not with YE.
[d] YE, a nice review.
[e-1] Thyrotropin receptor: "Lipoprotein from Yersinia enterocolitica
contains epitopes that cross-react with the human thyrotropin receptor."
{comment: My hunch is that the significance of this cross-
reactivity is that the child's antibodies against various
components of YE would include a tendency to attack his
thyrotropin receptors, which is very different from the
idea that anti-thyrotropin-receptor antibodies were
perceived by the lab as anti-YE antibodies.}
[e-2] Thyrotropin receptor cross-reactivity, plus two YE proteins are
mitogenic {for mouse spleen cells} and stimulate IL-6, IgG, and IgM production
and secretion.
[e-3] YE and other Yersinia strains produce molecules which are cross-
reactive with thyrotropin receptors.
{comment: If a person close to an autism-spectrum child has
Graves disease or is hyperthyroid to a lesser degree, then
there is the possibility that the autism-spectrum child
acquired a Yersinia colonization and, in some cases, the
infection might have become chronic within monocytes,
thereby creating an ongoing immune impairment.}
[e-4,5] Initial demonstration of YE cross-reactivity with thyrotropin receptor
and with anti-YE IgG levels.
[e-6] Various bacteria, including YE which does not necessarily reside in
the gut, bind TSH.
[f-1,2,3,4] Dogs, pigs, milk, and hospitals are among sources of YE.
[g] Many bacteria species share numerous cell-wall components, thus would have
to potential for "fooling" an antibody-assay. The lab director could be asked
about the specificity of the lab's YE assay.
[h] Yersinia can be organ specific and can cause abdominal pain.
[i] Th1 cytokines tend to inhibit Yersinia infections, Th2 cytokines (eg, IL4,
IL10) tend to induce conditions conducive to chronic Yersinia.
[j-1,2] YE generates a wide range of antibody specificities, and a small
sequence is common to a portion of HLA-B27 and occurs within several other
bacteria: "Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella
and Klebsiella within the same region of HLA alpha 1-helix."
[k] At the time of testing, diarrhea does not necessarily occur in YE
infections among children.
[l] In an Italy-based study, appx 10% of adults had YE antibodies in the range
of 1:20 to 1:40, thus offering perspective for a child with YE antibodies
substantially higher. The article cited here offers comparative data from other
studies but does not summarize that data in the abstract.
[m] That some individuals are YE carriers is known.
{Comment: in-utero or neonatal exposure, whether by a
family member or in a hospital, etc, would have the
potential for impairing immunity against the pathogen.}
For citations about this effect, see:
http://www.jorsm.com/~binstock/CD5-iga.htm
Teresa Binstock
Researcher in Developmental and Behavioral Neuroanatomy
References
[a-1] J Appl Microbiol 1999 May;86(5):731-40 The serodiagnosis of infections caused by Verocytotoxin-producing Escherichia coli. Chart H, Jenkins C Laboratory of Enteric Pathogens, Central Public Health Laboratory, London, UK. Patients with haemolytic uraemic syndrome (HUS) and haemorrhagic colitis (HC) produce serum antibodies to the lipopolysaccharides (LPS) of Escherichia coli O157 and certain other E. coli serogroups. Patients may also make salivary antibodies to the LPS of E. coli O157. Serological tests based on these antibodies can be used to provide evidence of infection in the absence of culturable VTEC or the toxins they produce. Serum antibodies to LPS persist for several months following onset of disease, enabling both current and retrospective serological testing. The LPS of E. coli O157 shares epitopes with strains of Brucella abortus, Yersinia enterocolitica O9, Vibrio cholerae O1 Inaba, group N Salmonella and certain strains of Citrobacter freundii and E. hermanni. Serological tests for serum antibodies to E. coli O157 should be evaluated in the light of these cross-reactions. Serological tests to supply evidence of infection with E. coli O157 have been shown to provide a valuable adjunct to bacteriological procedures for detecting culturable VTEC and VT. The use of well characterized LPS antigens in association with the techniques of ELISA and immunoblotting provide valuable procedures for detecting evidence of infection with E. coli O157 and possibly other VTEC. Publication Types: Review Review, academic PMID: 10347867, UI: 99277215 [a-2] J Clin Microbiol 1997 Mar;35(3):679-84 Production and characterization of monoclonal antibodies specific for the lipopolysaccharide of Escherichia coli O157. Westerman RB, He Y, Keen JE, Littledike ET, Kwang J U.S. Meat Animal Research Center, Agricultural Research Service, U.S. Department of Agriculture, Clay Center, Nebraska 68933, USA. Identification of the O157 antigen is an essential part of the detection of Escherichia coli O157:H7, which is recognized as a major etiologic agent of hemorrhagic colitis. However, polyclonal antibodies produced against E. coli O157:H7 lipopolysaccharide (LPS) may react with several other bacteria including Brucella abortus, Brucella melitensis, Yersinia enterocolitica O9, Escherichia hermannii, and Stenotrophomonas maltophilia. We produced eight monoclonal antibodies (MAbs) specific for the LPS of E. coli O157. Western blots (immunoblots) of both the phenol phase (smooth) and the aqueous phase (rough) of hot phenol-water-purified LPS indicated that three of the MAbs were specific for the O antigen and five were reactive with the LPS core. The eight MAbs could be further differentiated by their reactivities to Salmonella O30 LPS (group N), which is reported to be identical to the E. coli O157 antigen. All eight MAbs reacted strongly to all of the 64 strains of E. coli O157 tested, which included 47 isolates of O157:H7 and 17 other O157 strains. None of the eight MAbs cross-reacted with any of the 38 other E. coli serotypes tested, which consisted of 29 different O-antigen serotypes, or with 38 strains (22 genera) of non-E. coli gram-negative enteric bacteria. PMID: 9041412, UI: 97193827 [a-3] Epidemiol Infect 1991 Oct;107(2):349-56 The serological relationship between Yersinia enterocolitica O9 and Escherichia coli O157 using sera from patients with yersiniosis and haemolytic uraemic syndrome. Chart H, Cheasty T, Cope D, Gross RJ, Rowe B Division of Enteric Pathogens, Central Public Health Laboratory, London, UK. Sera from patients with yersiniosis, shown to contain antibodies to Yersinia enterocolitica O9; and sera from patients with haemolytic uraemic syndrome (HUS) caused by Escherichia coli O157, were used to investigate serological cross-reactions between Y. enterocolitica O9 and E. coli O157. Lipopolysaccharide (LPS) was isolated from strains of Y. enterocolitica O9 and E. coli O157 and reacted with sera by immunoblotting and ELISA. Sera from patients with HUS contained antibodies to the LPS of E. coli O157 only; 80% of sera from patients with yersiniosis contained antibodies to the LPS of Y. enterocolitica O9 and E. coli O157. This one-way cross-reaction was also detected using hyperimmune rabbit antisera. PMID: 1936156, UI: 92037886 [b] Vet Microbiol 1998 Feb 15;60(1):45-57 Serological cross-reactivity between Brucella abortus and yersinia enterocolitica 0:9: IV. Evaluation of the M- and C-epitope antibody response for the specific detection of B. abortus infections. Kittelberger R, Bundesen PG, Cloeckaert A, Greiser-Wilke I, Letesson JJ Central Animal Health Laboratory, Wallaceville Animal Research Centre, Upper Hutt, New Zealand. kittelbergerr@wallaceville.mqm.govt.nz Smooth lipopolysaccharides (SLPS) from Brucella abortus contain A-epitopes against which the majority of serum antibodies are directed during infections. SLPS from Yersinia enterocolitica 0:9 possesses identical epitopes, which are the cause for serological cross-reactivity. All Brucella spp. possess M- and C-epitopes which are not present in Y. enterocolitica 0:9. In order to examine the usefulness of these M- and C-epitopes for discriminatory serological testing, a panel of sera were used in this study, comprising sera from Y. enterocolitica 0:9-infected heifers, sera from B. abortus-infected cattle of comparable strength in the serological brucellosis tests to the sera from Y. enterocolitica 0:9-infected heifers, sera from B. abortus-infected bovines with strong serological reactions and sera from animals free from B. abortus or Y. enterocolitica infections. These sera were tested in blocking ELISAs with seven M- and one C-epitope-specific monoclonal antibodies in combination with SLPS from B. melitensis M16 high in M-epitopes as antigen. Strong B. abortus sera inhibited most strongly, while negative sera showed no or little inhibition. Sera with weak or intermediate titres blocked to a lower extent. Unexpectedly, the sera from Y. enterocolitica 0:9-infected heifers showed inhibition behaviour virtually identical to the comparable sera from B. abortus infected animals. Absorbing out of the A-epitope specific serum antibodies with either Y. enterocolitica 0:9 SLPS or with Y. enterocolitica 0:9 bacteria, indicated the presence of M- or C-epitope-specific serum antibodies in some sera from B. abortus-infected cattle but not in the sera from Y. enterocolitica 0:9-infected animals. These results demonstrate that the M- or C-epitope-specific antibody response in sera from B. abortus infected cattle is only of limited value for the serological discrimination between B. abortus and Y. enterocolitica 0:9 infections. PMID: 9595626, UI: 98257990 [c] Immunol Invest 1998 Jan-Feb;27(1-2):17-29 Relationship between HLA antigens and infectious agents in contributing towards the development of Graves' disease. Kraemer MH, Donadi EA, Tambascia MA, Magna LA, Prigenzi LS Department of Clinical Pathology, School of Medical Sciences, UNICAMP, Campinas, S.P., Brazil. Graves' disease (GD) is an autoimmune thyroid disorder which is associated with the human leucocyte antigens HLA-DR3 and DQA1* O501 in Caucasians. We have explored the possibility that some patients with certain HLA specificities develop anti-HLA antibodies which are correlated with environmental factors that may contribute to the development of GD. We studied 40 GD patients and 157 healthy individuals (controls). Serology was used to type HLA-A, -B, -Cw, and -DR antigens. The frequencies of these antigens in relation to lymphocytotoxic anti-HLA-A-B-Cw-DR antibodies and two environmental factors (Yersinia enterocolitica and Coxsackie B virus) were determined. The frequencies of HLA-B15, -B21 and DR3 antigens were increased, whereas HLA-DR5 antigen was decreased in GD patients. A significant association between HLA-DR3 antigen and lymphocytotoxic antibodies was observed, i.e., IgGs from GD patients were cytotoxic to HLA-DR3+ normal B cells. Following absorption with Yersinia enterocolitica or Coxsackie-B-virus, only Coxsackie-B virus completely inhibited the lymphocytotoxic reactions against HLA-DR3+ B cells. Besides confirming the association of HLA-DR3 with GD, this study also suggests the role of Coxsackie-reactive HLA-DR3 antibodies as contributing factors to the pathogenesis of the disease. PMID: 9561915, UI: 98222728 [d] Clin Microbiol Rev 1997 Apr;10(2):257-76 Yersinia enterocolitica: the charisma continues. Bottone EJ Department of Medicine, Mount Sinai Medical Center, New York, New York 10029, USA. Yersinia enterocolitica, a gram-negative coccobacillus, comprises a heterogeneous group of bacterial strains recovered from animal and environmental reservoirs. The majority of human pathogenic strains are found among distinct serogroups (e.g. O:3, O:5,27, O:8, O:9) and contain both chromosome- and plasmid (60 to 75 kb)-mediated virulence factors that are absent in "avirulent" strains. While Y. enterocolitica is primarily a gastrointestinal tract pathogen, it may produce extraintestinal infections in hosts with underlying predisposing factors. Postinfection sequelae include arthritis and erythema nodosum, which are seen mainly in Europe among patients with serogroups O:3 and O:9 infection and HLA-B27 antigen. Y. enterocolitica is acquired through the oral route and is epidemiologically linked to porcine sources. Bacteremia is prominent in the setting of immunosuppression or in patients with iron overload or those being treated with desferrioxamine. metastatic foci following bacteremia are common and often involve the liver and spleen. Of particular concern is blood transfusion-related bacteremia. Evidence has accumulated substantiating the role of Y. enterocolitica as a food-borne pathogen that has caused six major outbreaks in the United States. The diagnosis of Y. enterocolitica gastroenteritis is best achieved through isolation of the bacterium on routine or selective bacteriologic media. When necessary, serogrouping, biogrouping, and assessment for plasmid-encoded virulence traits may aid in distinguishing virulent from "avirulent" strains. Epidemiologically, outside of identified food-borne outbreaks, the source (reservoir) of Y. enterocolitica in sporadic cases is speculative. Therefore, prevention and control measures are difficult to institute. Publication Types: Review Review, academic PMID: 9105754, UI: 97259654 [e-1] J Immunol 1997 Feb 15;158(4):1976-83 Lipoprotein from Yersinia enterocolitica contains epitopes that cross-react with the human thyrotropin receptor. Zhang H, Kaur I, Niesel DW, Seetharamaiah GS, Peterson JW, Prabhakar BS, Klimpel GR Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA. Yersinia enterocolitica has recently been shown to produce a low molecular mass envelope protein that contains an epitope(s) that is cross-reactive with the extracellular domain of the human thyrotropin receptor (ETSHR). In this study, we have generated mAb to this cross-reactive protein and have obtained amino acid sequences for peptide fragments obtained from Lys-c digestion of the protein. The amino acid sequences of these peptides were identical to sequences present in bacterial lipoprotein (LP). All bacteria of the Enterobacteriaceae family produce LP as a major outer membrane protein. However, the ETSHR cross-reactive epitope(s) was shown to be unique to LP produced by Yersinia species. This was shown by Western blot analysis using a mAb specific for LP and with affinity-purified Ab specific for either LP or ETSHR and obtained from mouse antiserum generated to Y. enterocolitica. LPs from different Gram-negative bacteria were shown to be mitogenic for C3H/HeJ spleen cells and induced production and secretion of significant levels of Ig. Production of Ab that recognized the ETSHR was only induced in spleen cells stimulated with the LP obtained from Yersinia. In contrast, LP was not mitogenic for either human PBMC or human B cells. However, LP did induce IL6 and IL8 production in human monocytes at levels equivalent to that seen after LPS activation. These results identify, for the first time, the Yersinia envelope protein that is cross-reactive with the ETSHR and show that it can activate human monocytes. These findings are potentially important for advancing our understanding of the role molecular mimicry plays in the induction of autoimmunity to the thyrotropin receptor. PMID: 9029141, UI: 97180923 [e-2] J Autoimmun 1996 Aug;9(4):509-16 Yersinia enterocolitica envelope proteins that are crossreactive with the thyrotropin receptor (TSHR) also have B-cell mitogenic activity. Zhang H, Kaur I, Niesel DW, Seetharamaiah GS, Peterson JW, Justement LB, Prabhakar BS, Klimpel GR Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555-1019, USA. Autoantibodies to the thyrotropin receptor (TSHR) have been shown to mediate the hyperthyroidism associated with Graves' disease (GD). A number of hypotheses have been proposed which link an infectious agent to the mechanism(s) involved in the induction of GD. Several studies have suggested that the development of GD may be linked to infection with the enteric pathogen Yersinia enterocolitica. We have recently identified two low molecular weight (5.5 and 8 kDa) envelope proteins of Y. enterocolitica that are cross-reactive with the extracellular domain of human TSHR (ETSHR). In this study, we have purified these ETSHR-crossreactive Yersinia proteins (TSHR-CRP) and have further characterized their immunoreactivity. Both the 5.5 and 8 kDa TSHR-CRPs were shown to be mitogenic for mouse spleen cells. This mitogenic activity was specific for B cells and was not due to lipopolysaccharide (LPS) contamination. TSHR-CRPs were mitogenic for LPS-non-responsive spleen cells obtained from C3H/Hej mice, and polymyxin B did not inhibit the mitogenic activity of the TSHR-CRPs. TSHR-CRPs also induced high levels of IL-6 production in B cells and induced production and secretion of significant levels of IgG and IgM. Finally, culture supernatants from TSHR-CRP-stimulated spleen cells were shown by Western blot analysis to contain antibodies that recognized the ETSHR These results identify for the first time two envelope proteins of Yersinia that have mitogenic activity and therefore could represent important proteins involved in the pathogenesis of Yersinia infections. Because these mitogenic proteins also contain epitopes crossreactive with the TSHR, they are potentially important for advancing our understanding of the role molecular mimicry plays in the induction of autoimmunity to the TSHR. PMID: 8864826, UI: 97018210 [e-3] J Immunol 1994 Mar 1;152(5):2555-61 Purification and characterization of Yersinia enterocolitica envelope proteins which induce antibodies that react with human thyrotropin receptor. Luo G et al. Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston 77555. Graves' disease is an autoimmune disease mediated by autoantibodies to the thyrotropin receptor (TSHR). Several studies have suggested that the development of Graves' disease may be linked to infection with the enteric pathogen Yersinia enterocolitica. Using the purified recombinant extracellular domain of human TSHR (ETSHR), we have recently shown that immunization of mice with Y. enterocolitica results in the production of antibodies capable of reacting with the ETSHR. In this study, we identify two low molecular weight (5.5 kDa and 8 kDa) envelope proteins of Yersinia containing epitopes that are crossreactive with the TSHR. Identification of these crossreactive envelope proteins was achieved by Western blotting using affinity-purified anti-Y. enterocolitica antibodies that specifically react with the TSHR and, conversely, for envelope proteins of Yersinia. Confirmation that these Yersinia proteins contained crossreactive epitopes with the ETSHR was obtained by immunizing mice with partially purified envelope proteins, which resulted in the production of Abs that recognized the ETSHR. Further, some of the cross-reactive envelope proteins were purified with SDS-PAGE and HPLC. The crossreactive envelope proteins were shown to be chromosomally encoded, exposed on the surface of bacteria, and produced by virulent as well as avirulent strains of Yersinia (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica VW+, and Y. enterocolitica VW-). These results identify for the first time the Yersinia envelope proteins that are crossreactive with the ETSHR. Availability of these proteins will allow future studies to determine whether patients with Graves' disease have a unique immune response against these proteins when compared with healthy individuals. PMID: 7510749, UI: 94179839 [e-4] J Immunol 1993 Jul 15;151(2):922-8 Immunization of mice with Yersinia enterocolitica leads to the induction of antithyrotropin receptor antibodies. Luo G, Fan JL, Seetharamaiah GS, Desai RK, Dallas JS, Wagle N, Doan R, Niesel DW, Klimpel GR, Prabhakar BS Department of Microbiology, University of Texas Medical Branch, Galveston 77555-1019. It is well established that autoimmune Graves' disease, which is characterized by hyperthyroidism, is mediated by autoantibodies to the thyrotropin receptor (TSHr). Although what initially triggers this autoantibody response is not known, a number of studies have suggested that Yersinia enterocolitica, an enterobacteria, could initiate the immune response against the TSHr. In this study, we produced antibodies against purified extracellular domain of human TSHr (ETSHr) and showed that anti-ETSHr antibodies reacted with envelope preparations from Y. enterocolitica... Our studies provide the first direct evidence that immunization with Y. enterocolitica can lead to the production of antibodies capable of reacting with TSHr and might provide the initial stimulus necessary for breakdown of self-tolerance to TSHr, eventually leading to the development of autoimmunity to TSHr. PMID: 8335920, UI: 93329088 [e-5] Thyroid 1991 Winter;1(4):315-20 Immunoglobulins of patients recovering from Yersinia enterocolitica infections exhibit Graves' disease-like activity in human thyroid membranes. Wolf MW, Misaki T, Bech K, Tvede M, Silva JE, Ingbar SH Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts. Substantial evidence suggests a link between infections with Yersinia enterocolitica (YE) and Graves' disease. We have now examined the sera of 72 patients recovering from YE infection for immunoglobulins that interacted with the TSH receptor in human thyroid membranes. Compared with controls, in concentrations between 1 and 4 mg/mL, patient IgG produced a significant, concentration-dependent inhibition of TSH binding (p less than 0.001) and stimulation of adenylate cyclase activity (p less than 0.005-0.05). Whereas IgG from normal individuals caused no stimulation of adenylate cyclase, IgG from controls caused some concentration-dependent displacement of TSH, as previously reported. However, IgG from convalescents of YE infections was significantly more potent than normal IgG in reducing the binding of TSH to the membrane. Thus, at each examined concentration, YE patients' IgG displaced more TSH than IgG from normal controls. For each milligram per milliliter increment of IgG in the assay, patients' IgG caused a 10.2% inhibition of TSH binding (r -0.90, p less than 0.001), significantly greater than that seen with normal IgG (p less than 0.02). The present studies provide the first demonstration that IgG of patients recovering from YE infections react with the human TSH receptor. The antibodies presumably are produced against the TSH-binding protein present in YE. However, in view of lack of evidence for thyroid dysfunction in the sera of patients recovering from yersiniosis and the presence of TSH-binding proteins in other bacteria, we postulate that infection with YE is neither necessary nor sufficient to cause thyroid autoimmune disease. PMID: 1688156, UI: 93044564 [e-6] J Endocrinol 1989 Jun;121(3):571-7 Thyrotrophin (TSH)-binding proteins in bacteria and their cross-reaction with autoantibodies against the human TSH receptor. Byfield PG, Davies SC, Copping S, Barclay FE, Borriello SP Endocrinology Research Group, Clinical Research Centre, Harrow, Middlesex. A screen of a range of bacteria normally found in gut flora identified eight with the ability to bind TSH specifically. These included the previously reported Yersinia enterocolitica, Gram-positive, Gram-negative, pathogenic and commensal organisms. Eleven preparations of TSH-receptor autoantibodies strongly able to displace 125I-labelled TSH from the mammalian TSH receptor differed in their ability to displace the tracer from binding to bacterial extracts. None could displace the tracer from E. coli 06-1, four displaced 125I-labelled TSH from E. coli V21/1 and five displaced the tracer from Y. enterocolitica. Of those immunoglobulin preparations which did react with the bacterial protein, their apparent potency compared with that of TSH in displacing tracer from bacterial binders was an order of magnitude greater than with the mammalian receptor. This is consistent with the autoantibodies having a relatively better fit with the bacterial antigen than with the receptor when compared with TSH. The bacterial-binding activity and mammalian receptor-binding activities in each of two samples co-chromatographed on a Remazol yellow GGL-Sepharose affinity column strongly indicated that the same immunoglobulin species reacts with both antigens. These results are consistent with the proposal that a bacterial protein is the primary immunogen for the TSH-receptor antibodies in at least some patients with Graves' disease. PMID: 2754380, UI: 89328291 [f-1] Epidemiol Infect 1994 Dec;113(3):471-7 Duration of carriage and transmission of Yersinia enterocolitica biotype 4, serotype 0:3 in dogs. Fenwick SG, Madie P, Wilks CR Department of Veterinary Pathology and Public Health, Massey University, Palmerston North, New Zealand. Human infections with pathogenic strains of Yersinia enterocolitica have been linked to contact with dogs excreting these microorganisms. This study examines the carriage and transmission of Y. enterocolitica biotype 4, serotype 03 in dogs. Fourteen 6-month-old cross-bred dogs were separated into 5 groups, 2 containing 4 dogs (I and II) and the others 2 dogs (III-V). Each of the 4 dogs in Group I and 2 of the dogs in Group II were inoculated orally with the test strain. Bacteriological examination of faecal samples showed that dogs can be readily infected and can carry the organism for up to 23 days. The two in-contact dogs in Group II started to shed the test organism after 5 days. Subsequent transfer of these dogs to Group III and those in Group III to Group IV showed that Y. enterocolitica biotype 4, serotype 03 can be readily transmitted between dogs. At no time did any of the dogs show clinical signs of infection. Group V served as a negative control for the trial. These findings suggest that dogs can carry Y. enterocolitica biotype 4, serotype 03 asymptomatically and hence might act as a potential source of infection for people. PMID: 7995357, UI: 95087705 [f-2] Scand J Work Environ Health 1992 Apr;18(2):128-32 Antibodies against Yersinia among farmers and slaughterhouse workers. Seuri M, Granfors K Department of Community Health and General Practice, University of Kuopio, Finland. 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. PMID: 1604274, UI: 92294820 [f-3] Infect Control Hosp Epidemiol 1992 Mar;13(3):139-43 Yersinia enterocolitica infections in hospitalized patients: the problem of hospital-acquired infections. Cannon CG, Linnemann CC Jr Infection Control Department, University of Cincinnati Hospital, OH 45267-0788. OBJECTIVE: To study the epidemiology of Yersinia enterocolitica infections in hospitalized patients and to determine the frequency of hospital-acquired infection and the modes of transmission within the hospital. DESIGN: Descriptive study in which the clinical microbiology laboratory reported all positive Yersinia cultures to the infection control department; each case was investigated to determine the source of infection. SETTING: A 700-bed university teaching hospital. PARTICIPANTS: All patients who were culture-positive for Y enterocolitica after admission to the University of Cincinnati Hospital during the 4-year period between 1987 and 1990. RESULTS: Of 18 patients who were diagnosed with Yersinia infections, 8 (44%) were community-acquired. These patients were admitted with gastrointestinal symptoms and had their first positive cultures between days 1 and 5 of their hospitalizations. Five patients (28%) had hospital-acquired infections, having developed diarrhea after admission for unrelated problems, and became culture-positive between days 18 and 66. The remaining 5 patients could not be classified as either community- or hospital-acquired. These patients had gastrointestinal symptoms at the time of admission, but these could have been explained by other diseases. Their first positive stool cultures were not obtained until the second week or later during hospitalization, and 3 of these patients had negative stool cultures prior to a positive culture. CONCLUSIONS: Although Y enterocolitica has not previously been recognized as a common hospital problem, at least 28% of our patients acquired their Yersinia infections in the hospital. In some cases, cross infections, transmitted by healthcare workers, occurred between patients. Four of the 18 infections occurred in patients with acquired immunodeficiency syndrome. Comment in: Infect Control Hosp Epidemiol 1992 Mar;13(3):137-8 PMID: 1564310, UI: 92226499 [f-4] Epidemiol Infect 1990 Jun;104(3):345-50 Excretion of Yersinia spp. associated with consumption of pasteurized milk. Greenwood MH, Hooper WL Public Health Laboratory, Poole General Hospital. Yersinia enterocolitica biotype 1, serotype O.10K was isolated from 19 patients in the paediatric wards of a district general hospital over a period of 3 months. Fifteen cases were patients on the medical ward. Shortly afterwards, Y. enterocolitica biotype 1, serotype O.6, 30 was isolated from a further 17 patients on this ward in 1 month. The same serotypes of Y. enterocolitica were isolated from the pasteurized milk supplied to the ward. Epidemiological evidence indicated that contaminated pasteurized milk was the source of the yersinia organisms excreted by the patients. PMID: 2347379, UI: 90269375 [g] FEMS Microbiol Lett 1995 Jan 1;125(1):95-100 Variability of peptidoglycan structural parameters in gram-negative bacteria. Quintela JC, Caparros M, de Pedro MA Centro de Biologia Molecular Severo Ochoa, C.S.I.C., -U.A.M., Facultad de Ciencias (Biologia), U.A.M., Madrid, Spain. Muropeptide composition of peptidoglycan from the Gram-negative bacteria Aeromonas sp., Acinetobacter acetoaceticus, Agrobacterium tumefaciens, Enterobacter cloacae, Proteus morganii, Pseudomonas aeruginosa, Pseudomonas putida, Vibrio parahaemolyticus Yersinia enterocolitica and Escherichia coli, was analyzed by HPLC. In all instances peptidoglycan was built up from the same subunits. A wide disparity in the relative abundance of muropeptides and all structural parameters was observed. The contribution of LD-A2pm-A2pm cross-linked muropeptides was extremely variable; from 1 to 45% of cross-linked muropeptides. Muropeptides with the dipeptides Lys-Lys or Arg-Lys, indicative of murein-bound (lipo)proteins, were detected in all instances although abundance was very variable. PMID: 7867925, UI: 95172377 [h] J Pediatr Surg 1994 Dec;29(12):1621 Yersinia pseudotuberculosis affecting the appendix. Grant H, Rode H, Cywes S Department of Paediatric Surgery, Red Cross Children's War Memorial Hospital, Cape Town, South Africa. Yersinia pseudotuberculosis is an uncommon cause of abdominal pain. It has a much lower incidence than Yersinia enterocolitica, and most reports have emanated from Europe or North America. This report is about a patient with Yersiniosis affecting the appendix alone, in contrast to the usual picture of mesenteric adenitis or septicemia associated with this organism. PMID: 7877053, UI: 95182334 [i] Eur J Immunol 1992 Nov;22(11):2771-6 Predominance of Th1-type T cells in synovial fluid of patients with Yersinia-induced reactive arthritis. Schlaak J, Hermann E, Ringhoffer M, Probst P, Gallati H, Meyer zum Buschenfelde KH, Fleischer B First Department of Medicine, University of Mainz, FRG. The pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific for Yersinia enterocolitica are still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+ synovial fluid (SF)-derived T cell clones from 2 patients with Yersinia-induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)-gamma and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-gamma and thus belonged to the Th0 subset. Moreover, short-term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN-gamma and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN-gamma promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL-4. Furthermore, the Th2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-gamma and IL-2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection with Yersinia enterocolitica and, for the first time, reveal the cross-regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens. PMID: 1425904, UI: 93049611 [j-1] Dan Med Bull 1992 Apr;39(2):155-72 Interactions between Yersinia enterocolitica and the host with special reference to virulence plasmid encoded adhesion and humoral immunity. Paerregaard A Department of Clinical Microbiology, Rigshospitalet, Copenhagen. This thesis is based on 8 publications and a review of the literature. The aim was to summarize present knowledge on molecular components of Yersinia enterocolitica involved in (i) adhesion, with special reference to plasmid encoded factors and (ii) induction of antibodies in the host, and the quantitation of these two phenomena... A large number of antigens were identified in Y. enterocolitica by means of crossed immunoelectrophoresis (XIE)... infection with Y. enterocolitica induced an antibody response against a wide range of antigens... Publication Types: Review Review literature PMID: 1611921, UI: 92306734 [j-2] Clin Exp Immunol 1991 Dec;86(3):399-404 Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix. Lahesmaa R, Skurnik M, Vaara M, Leirisalo-Repo M, Nissila M, Granfors K, Toivanen P Department of Medical Microbiology, Turku University, Finland. 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. PMID: 1747948, UI: 92083644 [k] J Clin Microbiol 1991 Dec;29(12):2784-8 Yersinia enterocolitica isolated from two cohorts of young children in Santiago, Chile: incidence of and lack of correlation between illness and proposed virulence factors. Morris JG Jr, Prado V, Ferreccio C, Robins-Browne RM, Bordun AM, Cayazzo M, Kay BA, Levine MM Department of Medicine, University of Maryland School of Medicine, Baltimore 21201. Yersinia enterocolitica was isolated from children in two cohorts in Santiago, Chile. In a cohort containing a cross section of children aged 0 to 4 years, Y. enterocolitica was isolated from stool samples of 1.1% of children with diarrhea and 0.2% of age-matched control children. In a subgroup of this cohort from which weekly stool samples were obtained from all children irrespective of clinical status, 6% of children had asymptomatic Yersinia infections. In a birth cohort (with a greater representation of children less than 1 year of age and a significantly higher rate of diarrhea), Y. enterocolitica was isolated from 1.9% of children with diarrhea and 0.6% of controls (P = 0.05). Biogroup 1A strains (which lacked traditional phenotypic and molecular markers for pathogenicity) were isolated from seven children with diarrhea but from no control children in the birth cohort (P = 0.02). All other isolates, including all isolates from asymptomatic children, were "pathogenic" strains in biogroup 4, serogroup O3; no association between these isolates and occurrence of disease was found. Y. enterocolitica is found among young children in Santiago, with asymptomatic infections not uncommon occurrences. However, questions about the association between previously described virulence factors and diarrheal illness remain. PMID: 1757549, UI: 92098692 [l] Clin Ter 1991 Jul 31;138(2):87-90 [Prevalence of anti-Yersinia enterocolitica antibodies in an open population of the city of Rome]. [Article in Italian] Sebastiani L, Annicchiarico Petruzzelli B, Guglielmi A, Maldarizzi B Istituto di Igiene G. Sanarelli, Universita degli Studi di Roma, La Sapienza. This work shows the results of a seroepidemiological study of a group of 691 apparently healthy individuals: 246 males and 445 females from a Rome out-patient consulting center. 72 individuals (10.42%) were found positive with an antibody titer from 1:20 to 1:40. The percentages regarding the sexes and also those regarding the age groups did not show significant differences. The results of the research demonstrate a limited diffusion of Yersinia enterocolitica infection in the area under scrutiny. The results are correlated with those of similar researches. PMID: 1834405, UI: 92036157 [m] Transfusion 1991 Jul-Aug;31(6):500-1 Screening blood donors for gastrointestinal illness: a strategy to eliminate carriers of Yersinia enterocolitica. Grossman BJ, Kollins P, Lau PM, Perreten JL, Bowman RJ, Malcolm S, Palko WM American Red Cross, National Headquarters, Washington, DC.