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Biomedical subjects

A F Geczy

Publications and source records attributed to A F Geczy.

At least 55 records · Page 3Linked to original sources
PubMed1984

Persistence of HLA-B27 cross-reactive bacteria in bowel flora of patients with ankylosing spondylitis.

Previous studies have shown that antisera raised in rabbits to certain enteric bacteria (cross-reactive bacteria) are capable of specifically lysing in a 51chromium-release lymphocytotoxicity test the lymphocytes of HLA-B27-positive (B27+) patients with ankylosing spondylitis (AS). This study investigated the clinical relevance of this finding by ascertaining whether Escherichia coli isolated from the rectal swabs of 20 B27+ AS patients (B27+ AS+) and 46 controls (35 B27- AS- and 11 B27+ AS-) were able to absorb the lymphocytotoxic activity of these antisera. All isolates from B27+ AS+ patients and one from a B27- AS- individual were capable of removing this activity. These organisms persisted in the bowel flora of five selected patients for at least 9 months. Cross-reactive bacteria were also found in a range of gram-positive organisms, including streptococcal, staphylococcal, and clostridial species. The relevance of these findings is discussed in terms of a pathogenetic concept relating the persistence of cross-reactive bacteria in the bowel flora of B27+ individuals to an early event in the development of AS.

Antibodies, Bacterial↗
PubMed1984

A factor in the culture filtrate of some Klebsiella isolates specifically modifies the fibroblasts of HLA-B27-positive normal individuals.

Cultured skin fibroblasts of HLA-B27-positive clinically normal individuals specifically bind, and are modified by, a factor in the culture filtrate of some Klebsiella isolates. These modified fibroblasts are serologically similar to the cells (lymphocytes and fibroblasts) of B27-positive patients with ankylosing spondylitis (B27+AS+). By contrast, B27+AS+ cells fail to bind the factor, presumably because a receptor present on B27+AS- cells has already been blocked or modified by a Klebsiella antigen in vivo.

Cells, Cultured↗
PubMed1983

Is a Klebsiella plasmid involved in the aetiology of Ankylosing Spondylitis in HLA-B27-positive individuals?

The possibility that plasmid genes, carried by enteric organisms previously indirectly implicated as disease agents, play a role in the pathogenesis of Ankylosing Spondylitis (AS) was explored. A particular Klebsiella isolate (K21) previously found to cross-react with cells from HLA-B27 positive (B27+) patients with AS, but not with cells from normal individuals, was found to contain a plasmid(s). This coded for the organism's ability to produce a factor which could modify B27+ normal cells (AS-) rendering them lysable by the anti-Klebsiella serum. Curing of this isolate resulted in the loss of the plasmid concerned and a loss of ability of its culture filtrate to modify B27+ lymphocytes of clinically healthy subjects. When plasmids from K21 were transferred to a plasmid free laboratory strain, E. coli JP995, the recipient strain acquired the ability to elaborate modifying factor. These data suggest that plasmids, harboured by some enteric bacteria, and their products, may be implicated in modifying cells bearing certain Major Histocompatibility Complex genes, and that such modification may be an important factor in the pathogenesis of a number of diseases including the seronegative arthropathies.

Cross Reactions↗
PubMed1983

Enteric bacteria and HLA-B27 associated cell surface modification in patients with seronegative spondarthritis.

Cytotoxic studies indicate cross-reactivity between some enteric organisms and cells obtained from the majority of patients with ankylosing spondylitis. Preliminary studies suggest that the factor responsible for cross-reactivity may be generated by a bacterial plasmid. However, the mechanism mediating the interaction between the HLA-B27 positive cell and the bacterial antigen is at present unknown.

Cross Reactions↗
PubMed1983

A factor shed by lymphoblastoid cell lines of HLA-B27 positive patients with ankylosing spondylitis, specifically modifies the cells of HLA-B27 positive normal individuals.

Epstein-Barr virus transformed lymphoblastoid cell lines from HLA-B27 positive individuals with ankylosing spondylitis (B27+AS+) release, into the culture medium, a factor capable of specifically modifying the HLA-B27 positive lymphocytes of normal individuals (B27+AS-); this modification results in a phenotypic change similar to that seen on B27+AS+ lymphocytes. This lymphoblastoid cell line derived factor appears to be physically and functionally similar to a factor present in the culture filtrate of certain Klebsiella isolates. Biogel P-100 chromatography of the material released from the cell line indicated a mol.wt of 25,000-30,000, similar to that of the Klebsiella derived factor. Chromatofocusing on a PBE 94 column revealed that cell line derived factor had an isoelectric point of 5.5 (cf. pI 5.4 for the Klebsiella derived factor). Immunoadsorption experiments suggest that the factor from the B27+AS+ cell line shares antigenic determinants with a cell surface component present on certain Klebsiella isolates. These results will form the basis for future studies on the nature of the interaction between HLA-B27 and certain enteric organisms and their products. A better understanding of this association should elucidate some of the early events in the pathogenesis of the seronegative arthropathies.

Cell Line↗
PubMed1983

Genetic control of allogeneic interactions in the guinea-pig. V. Evidence for a dissociation between genes coding for A GPLA-B region-controlled determinant and genes coding for MLC suppressor cells.

The genetic basis of guinea-pig leucocyte antigen (GPLA)-B.2-associated unresponsiveness in the guinea-pig mixed leucocyte culture (MLC) was investigated using fibroblasts as stimulating cells. Guinea-pig foetal fibroblasts bearing the B.2 specificity can stimulate allogeneic but not syngeneic lymph node lymphocytes, whereas B.2-bearing peritoneal exudate cells (PEC) induce specific unresponsiveness. The inhibition of the mixed leucocyte-fibroblast reaction is seen only when the alloantisera are directed against the stimulatory fibroblast rather than the responding lymph node lymphocytes. Furthermore, B.2-bearing fibroblasts, in contrast to B.2-bearing PEC, fail to elaborate MLC-suppressor factor. It appears therefore, that in guinea-pig fibroblasts there is an apparent dissociation between major histocompatibility complex (MHC; in the region of the B locus) genes and the gene(s) coding for B.2-associated MLC suppressor cells and factor(s).

Animals↗
PubMed1982

Immunochemical characterization of Klebsiella antigens which specifically modify an HLA-B27-associated cell-surface component.

Culture filtrates of some Klebsiella isolates contain a factor(s) capable of specifically modifying the HLA-B27-positive lymphocytes of normal individuals, resulting in a phenotypic change similar to that seen on lymphocytes from patients with ankylosing spondylitis (AS). To further delineate the nature of the interaction between HLA-B27 and some Klebsiella products we have undertaken a chemical characterization of B27+AS+-cross-reactive Klebsiella antigens from the culture filtrate and the bacterial cell-membrane. Biogel P-100 chromatography of the Klebsiella K43-derived modifying factor from the culture filtrate and from an NP-40-solubilized membrane extract gave a molecular weight of 26,000-30,000. Isoelectric focusing revealed that the modifying factor had an isoelectric point of approximately 5.4. Membrane-associated modifying factor activity was found only in outer-membrane preparations indicating that the cross-reactivity between Klebsiella K43 and B27+AS+ cells is defined, at least in part, by outer-membrane antigens. These studies demonstrate that membrane components of Klebsiella K43 share antigenic determinants with a modifying factor, which is released into the culture medium, and that these components are capable of specifically altering the HLA-B27 antigen or an associated cell-surface structure. Such a modification occurring in vivo following exposure to Klebsiella, or to antigenically related organisms, could explain the triggering of the B27-associated arthropathies such as AS.

Antigens, Bacterial↗
PubMed1982

Genetic control of allogeneic interactions in the guinea-pig. IV. The specific elimination of MLC suppressor cells by the in vivo administration of antisera against a GPLA-B region-controlled determinant.

The in vivo effects of alloantisera, on the production of mixed leucocyte culture (MLC)-suppressor cells and suppressor factor (MLC-SF) as well as on the adoptive transfer of MLC suppression, were investigated. Intravenously administered anti-B.2 serum specifically eliminates B.2-associated MLC unresponsiveness and prevents the production of MLC-SF. By contrast, antisera directed against other B locus (homologous to the mouse H-2D or H-2K regions) or I region determinants do not appear to interfere with suppressor cell or factor production. Peritoneal exudate cells (PEC) from B.2-positive guinea-pigs can transfer MLC unresponsiveness to "normal' B.1-positive recipients; treatment of donor animals with anti-B.2 serum specifically prevents the transfer of MLC suppression. the results of this study support our earlier in vitro demonstration of B.2-bearing suppressor T cells which are sensitive to lysis by anti-B.2 sera in the presence of complement.

Animals↗
PubMed1981

Genes within the major histocompatibility complex of the guinea pig influence susceptibility to Trichostrongylus colubriformis infection.

The influence of genes in the major histocompatibility complex (MHC) of the guinea pig on the susceptibility to infection with the parasitic nematode Trichostrongylus colubriformis was investigated. Back-cross analysis of 2 lines of guinea pigs suggests that genes that map in or near the I region of the guinea pig MHC influence susceptibility to infection by the parasite. However, other genes, possibly not linked to the guinea pig MHC, may also be required for the full expression of susceptibility.

Animals↗
PubMed1981

Genetic control of allogeneic interactions in the guinea-pig. II. Evidence for alloantigen-specific suppressor cells in the guinea-pig mixed leukocyte culture.

The cellular basis of B.2-associated unresponsiveness in the guinea-pig MLC has been investigated. Macrophage-enriched and macrophage-depleted lymphoid cells were treated with alloantisera and complement and the ability of these antiserum-treated cell populations to present alloantigens to T lymphocytes investigated. It was found that B.2-specific suppressor cells can be eliminated from macrophage-depleted but not from macrophage-enriched stimulator cells with anti-B.2 serum and complement. By contrast, antiserum directed against allodeterminants on responding cells had no detectable influence on the MLC. Nylon wool column-purified B.2-specific T cells but not B.2-specific T cells, suppress the MLC between B.1-positive (stimulator cells) and B.2-positive (responding cells) lymphoid cells. Furthermore, anti-B.2 serum-treated column-purified B.2-specific T cells lose their ability to suppress the MLC reaction. It is concluded that B.2-specific MLC suppressor cells are T cells which are sensitive to lysis by alloantiserum in the presence of complement.

Animals↗
PubMed1981

The distribution of a specific HLA-B27-associated cell surface component on the tissues of patients with ankylosing spondylitis.

In this paper, we report the presence on Epstein-Barr virus-transformed lymphoblastoid cell lines on platelets and on fibroblasts of an HLA-B27-associated cell surface complex (antigenically related to some antigens of Klebsiella K43 and K21) which is identical to or cross-reactive with the determinant present on the peripheral blood lymphocytes (PBL) of B27-positive patients with ankylosing spondylitis (AS). By contrast, no Klebsiella K43 markers could be demonstrated on the spermatozoa of B27+ AS+ individuals even though these cells expressed the HLA-B27 alloantigen. No B27-associated K43 antigen was detected on the erythrocytes of patients or of normal controls. The B27-associated membrane marker is still detectable on lymphoblastoid cell lines after 20 generations and on fibroblasts after about 10 generations. This finding implies that the continued expression of Klebsiella-modified B27 structure is generally determined and does not require the repeated exposure of the cell surface to Klebsiella antigen. These data suggest that certain non-lymphoid as well as lymphoid cells may be involved in the complex sequence of events leading to the clinical manifestation of AS.

Blood Platelets↗