Sensitive mass spectrometric procedure for the detection of bacterial cell wall components in rheumatoid joints

Pritchard, D. G.; Rl, Settine; Jc, Bennett

doi:10.1002/art.1780230514

Cited by 19 publications

(3 citation statements)

References 14 publications

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“…Regarding the pathogenesis of human rheumatoid arthritis, it should be emphasized that (i) the E. aerofaciens strains used here originate in the normal gut flora of humans, (ii) degradation products derived from the normal gut flora are present in the circulation of healthy individuals (21,22), and (iii) bacterial CW debris has been demonstrated in the synovial tissues of patients with inflammatory arthritis (23,26,29,34,47). Therefore, the bacterial composition of the individual intestinal flora might represent a crucial factor contributing to the potential role of intestinal bacteria in the pathogenesis of rheumatoid arthritis.…”

Section: Vol 69 2001mentioning

confidence: 99%

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

et al. 2001

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Two almost-identical strains of Eubacterium aerofaciens isolated from the normal human gut flora were used. The cell wall (CW) of one strain with a peptidoglycan (PG) type A4␣ induces chronic arthritis in the rat after a single intraperitoneal injection, whereas CW of the other with PG type A4␤ induces only a transient acute arthritis. The CW of the arthritogenic E. aerofaciens was a twofold-more-potent stimulator of the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣) and monocyte chemoattractant protein 1 (MCP-1) than the nonarthritogenic CW. After degradation with mutanolysin, the capacity of the arthritogenic PG to stimulate production of TNF-␣ and MCP-1 was significantly increased, whereas that of the nonarthritogenic PG was significantly decreased. In other words, after enzyme degradation the arthritogenic PG had a four-to fivefoldstronger stimulatory capacity than that of the enzyme-treated nonarthritogenic PG. These findings indicate that the arthritogenicity of CW or a PG is not dependent on the enzyme resistance alone but also on how the PG fragments released by enzyme degradation stimulate the production of proinflammatory cytokines.Bacterial cell wall (CW) arthritis induced by a single intraperitoneal (i.p.) injection of gram-positive CWs in the rats is an experimental model closely resembling human rheumatoid arthritis. Using this model, we have described two bacterial strains of the same species, Eubacterium aerofaciens, one with a CW causing chronic arthritis and another with a CW causing only a transient acute arthritis. Both strains were isolated as a part of the normal human intestinal flora. They are 100% identical by the 16S ribosomal DNA (rDNA) analysis and have slightly different cellular fatty acid and biochemical profiles, indicating that they are clones of the same species (53). Chronic arthritis can be induced by using peptidoglycan (PG)-polysaccharide polymers isolated from the CW. The significance of polysaccharides seems to be to protect PG from enzyme degradation (4, 10, 35, 52), and for the induction of chronic arthritis the chemical structure of the PG moiety is decisive (52). The E. aerofaciens CW causing chronic arthritis has a PG of type A4␣, and the CW of the strain causing only a mild, transient arthritis has a PG of type A4␤. These two strains of E. aerofaciens have been designated arthritogenic and nonarthritogenic strains, respectively (53).PG in gram-positive CWs consists of several layers (up to 70) of sugar chains containing N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) alternatively linked to each other by ␤-1,4-glycosidic bonds (Fig. 1). Stem peptides, also called muramyl peptides, are short peptides of four to five amino acids bound to MurNAc. PG and muramyl peptides possess multiple immune activities (3,17,24,25,42). For instance, PG can bind to CD14 (6) and to Toll-like receptor 2 (36, 51) to stimulate T cells and monocytes to produce inflammatory cytokines, including tumor necrosis factor alpha (TNF-␣), interleukin (IL-8), and monocyt...

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Section: Vol 69 2001mentioning

confidence: 99%

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

et al. 2001

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“…We have recently suggested that the presence of these antibodies might be the result of polyclonal activation induced by ligands acting non-specifically on T and/or B cells and not exclusively the result of a specific immune response [27], According to the Coutinho & Moller theory for induction of humoral immunity, the activation of B cells to antibody secretion is mediated by non-specific polyclonal B-cellactivating (PBA) ligands interacting with nonclonally distributed B-cell receptors, whereas the specificity of the humoral immune response is ensured by the binding properties of Ig receptors [11], It follows that high concentrations of PBA substances will induce the formation of polyclonal antibodies, revealing the complete V-gene repertoire of immunocompetent B cells [10], Later reports have demonstrated that antibodies against different autoantigens and against various chemical haptens can be induced by in vitro addition of PBA substances to human and mouse lymphocytes and by in vivo injection of mice witb these substances [19,20,25,31,42], These observations indicated that clones of autoreactive B cells exist normally and can be activated by PBA substances to secrete autoantibodies. The fact that PBA substances are mostly bacterial or viral in origin and the possibility that an unapparent viral or bacterial infection migbt be involved in the pathogenesis of autoimmune diseases [29,33,41] open the possibility for the presence of PBA substances in patients with RA,…”

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confidence: 99%

High Incidence of Spontaneous Ig‐Producing Lymphocytes in Peripheral Blood and Synovial Fluid of Patients with Active Seropositive Rheumatoid Arthritis

1982

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Numbers of in vitro spontaneous IgG, IgM and IgA plaque-forming cells (PFC) as assessed by a modification of the protein A haemolytic plaque assay were determined in the blood and synovial fluid of patients with seropositive rheumatoid arthritis (RA) and compared with those of control groups. The total numbers of PFC were significantly higher in the peripheral blood of patients with active seropositive RA than in that of normal controls. In addition, most B lymphocytes in the synovial fluid of patients with active seropositive RA were active immunoglobulin (Ig) producers, whereas synovial fluid lymphocytes from patients with inactive seropositive RA and seronegative arthritis were not. In general, IgA PFC were relatively high in blood, whereas IgG PFC dominated in the synovial fluid. IgM PFC appear to be relatively low in blood and synovial fluid. However, a relative increase of IgG PFC was noted in the peripheral blood of patients with active RA. To test for polyclonality of the increased Ig synthesis, we tested the sera of patients and controls for the presence of polyclonal antibodies against sheep erythrocytes (SRBC) and SRBC modified by fluorescein isothiocyanate (FITC) and trinitrophenyl (TNP). No differences were observed with SRBC and TNP-SRBC agglutinin titres between patients and controls, but patients with RA had higher titres of FITC-SRBC agglutinins than normal sera. This finding supports the concept of a polyclonal nature of antibody production in RA patients.

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“…Pritchard, Settine, and Bennett hypothesized that rheumatoid arthritis (RA) might also be related to the presence of persistent bacterial remnants; they proposed that if muramic acid derived from bacterial debris were detected in SF from patients with rheumatoid arthritis (RA), it would signal the presence of bacterial antigens (6,7). Their study has, until now, been the only one to assess muramic acid levels in human SF.…”

Section: Mass Spectrometric Quantitation Of Muramic Acid a Bacterialmentioning

confidence: 99%

Mass spectrometric quantitation of muramic acid, a bacterial cell wall component, in septic synovial fluids

Christensson

Gilbart

Fox

et al. 1989

Arthritis & Rheumatism

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This is the first report describing the use of gas chromatography-mass spectrometry for detection of muramic acid in infected synovial fluid (SF). Muramic acid is a ubiquitous component of bacterial cell walls, and it has been proposed that it could serve as a chemical marker for the presence of live bacteria or bacterial debris in rheumatoid joints. Our goal was to determine whether muramic acid was present at detectable levels in septic SF, since this would serve as a positive control for studies of reactive and rheumatoid arthritis. Muramic acid was found to be present at levels of <250-1,700 ng/ml in 12 septic SF samples (10 of which were culture positive for Staphylococcus aureus and 1 each for Escherichia coli and Streptococcus pneumoniae). Among these samples, those containing low bacterial colony counts did not contain detectable mu-

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Sensitive mass spectrometric procedure for the detection of bacterial cell wall components in rheumatoid joints

Cited by 19 publications

References 14 publications

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

High Incidence of Spontaneous Ig‐Producing Lymphocytes in Peripheral Blood and Synovial Fluid of Patients with Active Seropositive Rheumatoid Arthritis

Mass spectrometric quantitation of muramic acid, a bacterial cell wall component, in septic synovial fluids

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