Harmale Tiwana

Shared amino acid sequences between major histocompatibility complex class II glycoproteins, type XI collagen and Proteus mirabilis in rheumatoid arthritis.

OBJECTIVES--To show molecular similarity between two sequences of Proteus mirabilis (haemolysin--ESRRAL; urease--IRRET) with HLA-DR antigens (EQRRAA) which are associated with rheumatoid arthritis (RA) and type XI collagen (LRREI), respectively; and, in patients with RA, to measure levels of antibody against a 16-mer synthetic peptide containing the ESRRAL sequence, and the haemolysin and urease proteins of Proteus mirabilis. METHODS--The homologous sequences EQRRAA and ESRRAL were modelled with Alchemy III, using the crystalline structure of DRB1*0101 (HLA-DR1). Sera from 40 patients with RA, 30 with ankylosing spondylitis (AS), and 30 controls were tested against synthetic ESRRAL peptide and the haemolysin of Proteus mirabilis by enzyme linked immunosorbent assay. Similar tests were also carried out on sera from 20 patients with RA, 40 with AS, and 15 controls, against Proteus mirabilis urease. RESULTS--Molecular modelling of the homologous sequences ESRRAL/EQRRAA and IRRET/LRREI showed stereochemical similarities. Antibodies to the 16-mer synthetic peptide containing the ESRRAL sequence, the haemolysin, and urease proteins were significantly increased in RA patients compared with AS patients (p < 0.001) and healthy controls (p < 0.001). No such increases were observed with three control peptides including the EDERAA sequence of DRB1*0402 (HLA-DR4/Dw10), the haemolysin proteins of Streptococcus pyogenes and Vibrio parahaemolyticus, and the urease of Bacillus pasteurii. CONCLUSION--The additive effect of the immune responses to the two Proteus mirabilis antigens, haemolysin (ESRRAL) and urease (IRRET), could be relevant in the aetiopathogenesis of RA.

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.

Role of Klebsiella and collagens in Crohn's disease: a new prospect in the use of low-starch diet.

Crohns disease is suggested to result from a microbially triggered immune-mediated autoimmune process, involving mainly the terminal ileum and ileo-caecal junction. Klebsiella pneumoniae shares certain molecular structures present in pullulanase pulA and pulD secretion enzymes with various self-antigens present in collagens and HLA-B27 molecules, respectively. A link exists between high dietary starch intake and the growth of intestinal microflora, involving especially Klebsiella microbes. Increased exposure to Klebsiella in the gut as the result of high starch intake would lead to high production of antiKlebsiella antibodies as well as autoantibodies to the cross-reactive self-antigens with the resultant inflammation at the pathological sites. Eradication of these microbes from the gut in patients with Crohns disease with the use of low-starch diet and antibacterial agents as well as immunomodulatory measures could be beneficial in the management of this disease.

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

Abstract 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 nitrogenase reductase in patients with ankylosing spondylitis

The strong link between ankylosing spondylitis (AS) and HLA-B27 has been well established.1 Any aetiological agent or mechanism implicated in AS must provide an explanation for the link with HLA-B27. An amino acid sequence homology, QTDRED, found in the variable region of B*2705, (residues 72–77) and the KP2 component of Klebsiella pneumoniae nitrogenase enzyme (residues 188–193) has been reported.2 Furthermore, AS patients were shown to have increased concentrations of antibodies to a homologous sequence of both B*27052 3 and the KP2 component of K pneumoniae nitrogenase reductase2 although some workers have been unable to confirm these results.4 Antibody affinity is often lower with peptide sequences compared with binding by the native protein and this could be because of conformational changes between peptide and the native protein molecule, thereby accounting for these differences in reactivity. In the light of these conflicting findings, this study was undertaken to measure antibodies to the native KP2 component of nitrogenase reductase enzyme of K pneumoniae , to determine if it has a …