The ancient practice of sutra neti leading to velopharyngeal stenosis: case report.

BACKGROUND: An ancient yoga technique called sutra neti, which is extensively used in India to keep the sinuses healthy, led to complete velopharyngeal stenosis in a 67-year-old male patient who presented with bilateral nasal obstruction, mouth breathing, anosmia and a change in voice. METHOD: The patient was diagnosed by nasal endoscopy using a zero-degree Hopkins rod endoscope, and adhesions were released using coblation. RESULTS: The patient had post-operative alleviation of symptoms and a patent velopharyngeal inlet on examination. CONCLUSION: Vigorous sutra neti can lead to velopharyngeal stenosis. Release of the stenosis is then required to cure the nasal blockade.

The immunogenicity of a conformationally restricted peptide mimetic of meningococcal lipooligosaccharide.

Life-threatening meningitis and septicaemia caused by Neisseria meningitidis are a public health priority, and their prevention by vaccination is a major objective. Meningococcal capsular polysaccharide-based vaccines are effective against the major invasive serogroups, except for serogroup B, the capsule of which mimics human polysaccharides and is poorly immunogenic. An alternative vaccine candidate that has the potential to offer cross-protection against antigenically diverse meningococci is the lipooligosaccharide (LOS). The structurally constrained peptide mimetic, C22, of a bactericidal antibody epitope within LOS was previously shown to elicit cross-reactive antibodies to meningococcal LOS when complexed to NeutrAvidintrade mark as a carrier protein. The immunogenicity of this antigen in H-2(d) (BALB/c) and H-2(k) (C3H/HeN) haplotype mice was further investigated. Anti-LOS immunoglobulin G (IgG) antibody titres increased with the vaccine dose and correlated with the anti-C22 peptide antibody titres in both haplotypes. Antigen-stimulated Th1/Th2 cytokine secretion by splenocytes and antibody isotypes indicated a Th2-type immune response with IgG1 antibodies and a low titre of IgG2b. There was no serum bactericidal activity observed against the meningococcus.

Antibody responses to Acinetobacter spp. and Pseudomonas aeruginosa in multiple sclerosis: prospects for diagnosis using the myelin-acinetobacter-neurofilament antibody index.

Antibody responses to Acinetobacter (five strains), Pseudomonas aeruginosa, Escherichia coli, myelin basic protein (MBP), and neurofilaments were measured in sera from 26 multiple sclerosis (MS) patients, 20 patients with cerebrovascular accidents (CVA), 10 patients with viral encephalitis, and 25 healthy blood donors. In MS patients, elevated levels of antibodies against all strains of Acinetobacter tested were present, as well as antibodies against P. aeruginosa, MBP, and neurofilaments, but not antibodies to E. coli, compared to the CVA group and controls. The myelin-Acinetobacter-neurofilament antibody index appears to distinguish MS patients from patients with CVAs or healthy controls. The relevance of such antibodies to the neuropathology of MS requires further evaluation.

Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis.

BACKGROUND: Increased levels of collagen types I, III and V are found in strictures of patients with Crohn's disease (CD) compared with normal gut tissue. Type IV collagen is present in the basement membranes, basal lamina, retina and cornea. Elevated levels of antibody to Klebsiella pneumoniae are found in both active CD and active ankylosing spondylitis (AS) patients compared with healthy controls. METHODS: Reactivities for immunoglobulin class-specific antibodies (IgM, IgG and IgA) against collagen types I, III, IV, V and whole K. pneumoniae were measured by ELISA in nine patients with early CD and 10 with late CD from King's College Hospital and 12 late CD patients and 36 HLA-B27-positive AS patients from Middlesex Hospital and was compared with values for 26 healthy controls from the Blood Transfusion Service in London. RESULTS: Levels of class-specific IgM, IgG and IgA antibodies to collagen types I, III, IV, V and K. pneumoniae were significantly elevated in early and late CD patients compared with healthy controls (P<0.001). Levels of IgM, IgG antibody to the four collagen types and K. pneumoniae were also significantly elevated (P<0.001) in AS patients compared with healthy controls. In addition, the level of IgA antibody to K. pneumoniae was elevated in AS patients (P<0.001). Furthermore, a positive correlation between antibody levels to collagen types I, III, IV and K. pneumoniae was demonstrated in both early and late CD patients and in those with AS, whilst a positive correlation to type V was found in early CD. CONCLUSION: The role of K. pneumoniae and anti-collagen antibodies in the aetiopathogenesis of CD and AS requires further study.

Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity.

Molecular mimicry is one of the pathological mechanisms proposed to explain the association between microorganisms and autoimmune diseases. This review deals with the association between bacteria and rheumatic diseases with a special emphasis on rheumatoid arthritis where upper urinary tract infection by Proteus mirabilis is the possible cause of this severe, arthritic condition. Prospective trials involving anti-Proteus therapy should be carried out.

Genetic diversity in Proteus mirabilis isolates found in the urinary tract of rheumatoid arthritis patients.

OBJECTIVE: Elevated levels of anti-Proteus antibodies but not antibodies to E. coli have been reported in patients with rheumatoid arthritis (RA). The suggestion has been made that P. mirabilis may have a role in the aetiopathogenesis of rheumatoid arthritis. The aim of this study was to determine whether there are differences at the genetic level inisolates of P. mirabilis obtained from controls and RA patients. METHODS: A blind study was performed whereby P. mirabilis isolates obtained from urinary cultures of RA patients and controls were analysed using RAPD PCR. Isolates were then grouped on the basis of their DNA band profile after agarose gel electrophoresis, thereby allowing the composition of the Proteus population in the urinary tract to be analysed at the genetic level. RESULTS: Fourteen different DNA band profiles were obtained from the 93 isolates tested: 70% of these isolates fell into only five of the 14 groups and approximately 25% of all isolates fell into one group. No differences were observed in the frequency of isolates from either control or RA subjects. CONCLUSIONS: There is genetic diversity in P. mirabilis populations found in the urinary tract, but there are no differences in the frequency of these bacteria between RA patients and controls.

Autoantibodies to brain components and antibodies to Acinetobacter calcoaceticus are present in bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE) is a neurological disorder, predominantly of British cattle, which belongs to the group of transmissible spongiform encephalopathies together with Creutzfeldt-Jakob disease (CJD), kuru, and scrapie. Autoantibodies to brain neurofilaments have been previously described in patients with CJD and kuru and in sheep affected by scrapie. Spongiform-like changes have also been observed in chronic experimental allergic encephalomyelitis, at least in rabbits and guinea pigs, and in these conditions autoantibodies to myelin occur. We report here that animals with BSE have elevated levels of immunoglobulin A autoantibodies to brain components, i.e., neurofilaments (P < 0.001) and myelin (P < 0.001), as well as to Acinetobacter calcoaceticus (P < 0.001), saprophytic microbes found in soil which have sequences cross-reacting with bovine neurofilaments and myelin, but there were no antibody elevations against Agrobacterium tumefaciens or Escherichia coli. The relevance of such mucosal autoantibodies or antibacterial antibodies to the pathology of BSE and its possible link to prions requires further evaluation.

Cross-reactivity between the rheumatoid arthritis-associated motif EQKRAA and structurally related sequences found in Proteus mirabilis.

Cross-reactivity or molecular mimicry may be one of the underlying mechanisms involved in the etiopathogenesis of rheumatoid arthritis (RA). Antiserum against the RA susceptibility sequence EQKRAA was shown to bind to a similar peptide ESRRAL present in the hemolysin of the gram-negative bacterium Proteus mirabilis, and an anti-ESRRAL serum reacted with EQKRAA. There was no reactivity with either anti-EQKRAA or anti-ESRRAL to a peptide containing the EDERAA sequence which is present in HLA-DRB1*0402, an allele not associated with RA. Furthermore, the EQKRAA and ESRRAL antisera bound to a mouse fibroblast transfectant cell line (Dap.3) expressing HLA-DRB1*0401 but not to DRB1*0402. However, peptide sequences structurally related to the RA susceptibility motif LEIEKDFTTYGEE (P. mirabilis urease), VEIRAEGNRFTY (collagen type II) and DELSPETSPYVKE (collagen type XI) did not bind significantly to cell lines expressing HLA-DRB1*0401 or HLA-DRB1*0402 compared to the control peptide YASGASGASGAS. It is suggested here that molecular mimicry between HLA alleles associated with RA and P. mirabilis may be relevant in the etiopathogenesis of the disease.

Characterization of the humoral immune response to Klebsiella species in inflammatory bowel disease and ankylosing spondylitis.

This study was carried out to characterize the antibody class response by ELISA to seven Klebsiella pneumoniae serotypes (K2, K3, K17, K21, K26, K36, K50) in five different groups, 40 HLA-B27-positive ankylosing spondylitis (AS) patients, 46 patients with Crohn's disease (CD), 38 patients with ulcerative colitis (UC), 50 patients with active anti-endomysial antibody-positive coeliac disease and 40 healthy controls, using whole bacteria and capsular polysaccharide. IgG antibody levels were significantly elevated in AS patients to K17, K36, K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to serotype K21 when compared to normal controls. Furthermore, IgG antibody levels were significantly elevated in CD patients to K2, K17, K21, K26, K36 and K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to K2, K3, K17, K21 and K50. Increased IgG antibody levels in the UC group were limited only to K17, K36 and K50. No antibody class was increased to any of the K. pneumoniae serotypes in the coeliac disease group. The immune responses in AS patients also involve Klebsiella bacteria having capsular serotypes other than K26, K36 and K50. The similarity in the immune responses between CD and AS groups suggests that many AS patients may have occult bowel inflammation.

Antibiotic sensitivity and proticine typing of Proteus mirabilis strains associated with rheumatoid arthritis.

Urinary isolates of Proteus mirabilis, obtained from 49 RA patients and 44 healthy controls, were tested for susceptibility to antibiotics by the disc diffusion method. In addition, P. mirabilis isolates were also tested for proticine production and sensitivity (p/s) typing by the inhibition of growth of each test isolate against 13 reference strains of P. mirabilis. The P. mirabilis isolates from both RA patients and healthy controls were highly susceptible to norfloxacin, ciprofloxacin and trimethoprim, but less to minocycline. The urine of RA patients contained fewer different types of P. mirabilis strains than those isolated from healthy controls. All of the strains found in the RA patients were proticine producers (P < 0.001), mostly of proticine 3 (P < 0.005). The presence of such strains provides evidence of a sub-clinical upper urinary tract infection with P. mirabilis in some RA patients. Therapeutic intervention in RA with relevant antibiotics requires evaluation.

Antibodies to Klebsiella pneumoniae in Dutch patients with ankylosing spondylitis and acute anterior uveitis and to Proteus mirabilis in rheumatoid arthritis.

OBJECTIVE: To determine whether the association between increased humoral reactivity against Klebsiella and HLA-B27 associated diseases could be confirmed in Dutch patients with ankylosing spondylitis (AS) and acute anterior uveitis (AAU). METHODS: Under coded conditions sera from Dutch patients with AS, AAU, and rheumatoid arthritis (RA) and from HLA-B27 positive and negative healthy controls were studied for IgA anti-Klebsiella (K54) and IgG anti-Proteus antibodies with the indirect immunofluorescence assay on whole bacteria fixed in suspension with paraformaldehyde. Each group consisted of at least 17 sera. RESULTS: IgA anti-Klebsiella antibody titers were elevated in AS and HLA-B27 negative AAU compared to the HLA-B27 positive and negative controls or patients with active RA (p < 0.001). Furthermore, patients with active RA had elevated levels of IgG antibodies against P. mirabilis compared to every other test or control group (p < 0.001). There was no significant difference between the AS and RA patients in terms of serum C-reactive protein levels, although these were significantly elevated in both compared to healthy controls (p < 0.001), suggesting that the antibody elevations were not due to a nonspecific inflammatory effect. The same sera were blindly tested with negative results by 2 other centers. The discrepancies are probably the result of differences in the methods used. CONCLUSION: Our data support the hypothesis that Klebsiella are involved in the pathogenesis of AS and AAU and that the same might be true for Proteus in RA.

Antibodies to Klebsiella pneumoniae lipopolysaccharide in patients with ankylosing spondylitis.

The role of microbial lipopolysaccharides (LPS) in the aetiopathogenesis of ankylosing spondylitis (AS) is a matter of continuing debate. In this study, class-specific IgG, IgA and IgM antibodies against Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Salmonella enteritidis LPS were measured by enzyme-linked immunosorbent assay (ELISA) in 100 AS patients, 50 rheumatoid arthritis (RA) patients and 50 healthy control subjects. The AS patients had significantly elevated levels of IgG and IgA antibodies against K. pneumoniae LPS (P < 0.001) and IgA antibodies against E. coli LPS (P < 0.05) compared to healthy controls. There were no significant elevations of antibody levels against S. typhimurium and S. enteritidis in the three study groups. In addition, there was a correlation between IgG and IgA anti-K. pneumoniae LPS antibody levels and the acute-phase reactant C-reactive protein (P < 0.001).

Antibody responses to gut bacteria in ankylosing spondylitis, rheumatoid arthritis, Crohn's disease and ulcerative colitis.

Specific immunoreactive anti-Klebsiella antibodies are found in patients with ankylosing spondylitis (AS), a significant proportion of whom have occult inflammatory bowel disease. Molecular mimicry between Klebsiella or other bacterial antigens and HLA-B27 has been suggested in the pathogenesis of AS. The specificity of increased immunoreactivity against Klebsiella remains to be assessed against the abundant anaerobic bacterial flora, present either in healthy controls or in patients with ulcerative colitis (UC) and Crohn's disease (CD). Total immunoglobulin (Ig; IgG, IgA, IgM) immunoreactivity was measured by ELISA against Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli and ten anaerobic isolates of the predominant normal bowel flora in 35 patients with active AS, 60 patients with inflammatory bowel disease (30 CD, 30 UC), 60 patients with active rheumatoid arthritis (RA) and 60 healthy controls. Ig immunoreactivity to K. pneumoniae was significantly elevated in AS (P < 0.001), CD (P < 0.001) and UC (P < 0.001) patients compared with RA patients and healthy controls. Furthermore, Ig immunoreactivity to P. mirabilis was significantly elevated only in RA patients, compared with the other inflammatory groups (P < 0.001) and controls (P < 0.001). There was no significant antibody response against E. coli or the ten obligate anaerobes in any of the test groups. The data suggested an increased immune response to Klebsiella in patients with AS, UC, CD and to Proteus in patients with RA. The specificity of these responses in some patients supported a possible role for enteric Klebsiella in the pathogenesis of AS and Proteus in RA. The role of Klebsiella in inflammatory bowel disease requires further study.

Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: To determine whether patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) from Japan have antibodies to Klebsiella pneumoniae and Proteus mirabilis and to assess whether such antibodies are activated against peptides sharing sequences with HLA-B27. METHODS: Serum samples from 152 Japanese patients, 52 with AS, 50 with RA, and 50 healthy controls, were tested against 3 bacteria (K. pneumoniae, P. mirabilis, and Escherichia coli) and 3 synthetic peptides (HLA-B27, pullulanase-D, and scrambled pullulanase-D control peptide) by ELISA under coded conditions. Samples were tested for elevations in IgG, IgA, and IgM antibody classes in patients with active AS or RA, in patients with RA with probable disease, and in patients with inactive AS. Disease activity was determined by an elevated serum C-reactive protein (> 10 mg/l) level and elevated erythrocyte sedimentation rate (> 20 mm/h). RESULTS: Patients with active AS showed specific elevations in serum IgA antibody levels against K. pneumoniae compared to patients with RA and controls (p < 0.001). No such elevation was seen in the IgG and IgM antibody classes. Patients with inactive AS showed no elevation in any class of antibody against K. pneumoniae compared to controls or patients with RA. Patients with active or probably active RA showed significant elevations in IgG antibody levels against P. mirabilis compared to AS and controls (p < 0.001). Patients with AS (active or inactive), RA (active or probably active), and controls showed no elevations in any antibody class to E. coli. Both active and inactive AS patients had specific autoantibodies against HLA-B27 peptide compared to patients with RA and controls (active AS: IgG, IgA, IgM, p < 0.001; inactive AS: IgG and IgA, p < 0.001). Patients with active AS had IgG and IgA antibodies against pullulanase-D peptide, which contains a sequence that cross reacts with HLA-B27 compared to controls (p < 0.001). CONCLUSION: These results provide the first evidence of AS and RA patients in Japan having specific elevations of antibody to K. pneumoniae and P. mirabilis, respectively. This suggests that K. pneumoniae in AS and P. mirabilis in RA may play a role in triggering and/or exacerbating these diseases.

Antibodies to four gram-negative bacteria in rheumatoid arthritis which share sequences with the rheumatoid arthritis susceptibility motif.

The bacteria Proteus, Serratia, Escherichia and Pseudomonas possess sequences resembling the rheumatoid arthritis susceptibility sequence EQRRAA, but antibodies were elevated only to Proteus in 66 RA patients (P<0.001) when compared to 61 active ankylosing spondylitis patients and 60 controls.

Molecular mimicry: the geographical distribution of immune responses to Klebsiella in ankylosing spondylitis and its relevance to therapy.

The discovery that HLA-B27 is linked to ankylosing spondylitis (AS) and HLA-DR1/DR4 to rheumatoid arthritis (RA) has provided new approaches to the study of the possible causation of these diseases. Several theories have been proposed to explain these associations but only one, namely "molecular mimicry", has provided a specific aetiological agent for each of these diseases. Molecular mimicry between HLA-B27 and two molecules in Klebsiella microbes: nitrogenase and pullulanase D has been reported whilst in Proteus microbes, the haemolysin molecule shows sterochemical similarity to HLA-DR1/DR4. Elevated immune responses to Klebsiella microbes have been demonstrated in AS patients from 10 different countries and this wide geographical distribution suggests that the same aetiological agent is probably acting in producing this condition. Furthermore RA patients show similar immune responses to Proteus microbes. Whether AS or RA are caused by these bacteria can only be resolved by tissue typing all rheumatological patients early, in the course of their disease and then assessing their response to antibiotic chemotherapy in longitudinal studies involving double-blind crossover trials. It is possible that in the future, the course of AS or even RA could be modified by adequate antibiotic chemotherapy or even diets which affect the substrates on which these bacteria grow.