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Biomedical subjects

K Granfors

Publications and source records attributed to K Granfors.

172 records · Page 10Linked to original sources

Defect in the generation of light-chain diversity in bursectomized chickens.

The avian bursa of Fabricius has been regarded as a central organ for B-cell development, but there is controversy about the existence of other sites for differentiation of B cells. We have recently shown that chickens surgically bursectomized as early embryos, before the bursal primordium appears, can produce cytoplasmic, surface and serum immunoglobulins of IgM, IgG and IgA classes but are unable to generate specific antibodies in response to antigen. We have therefore examined the structure and diversity of immunoglobulins of bursectomized chickens. Analysis of serum IgG revealed normal gamma-heavy chains but altered light chains with more basic and less diverse isoelectric points than normal. These light chains may represent germ-line specificities not diversified by somatic mutations. Thus the bursa of Fabricius appears not to be necessary for the production of immunoglobulin molecules as such but to function in the creation and expansion of the antibody repertoire, possibly by providing a microenvironment for somatic mutations.

Animals↗

Serological cross-reactions against Yersinia enterocolitica in patients infected with other arthritis-associated microbes.

In order to investigate arthritis-triggering, serologically cross-reactive antigens, sera from patients infected with arthritis-associated microbes, Salmonellae, Chlamydia trachomatis, and Sindbis-like alphavirus, were reacted against SDS-PAGE separated and immunoblotted Yersinia enterocolitica 0:3 antigens. These sera reacted with Yersinia to the same extent as did the control sera taken from patients with streptococcal, staphylococcal and Bordetella pertussis infections or from healthy blood donors. Moreover, the various sera produced different reactivity patterns, directed against several different antigens. Although sera from test subjects, as well as from controls including healthy individuals, recognized some Yersinia antigens, these patterns differed markedly from those recognized by sera taken from patients with Yersinia infection. Significantly, analysis of the reactivities against the different molecular weight antigen components of Yersinia revealed no dominant band or pattern which could thus have been defined as arthritis-associated.

Adult↗

Yersinia antibodies in inflammatory joint diseases.

The occurrence of IgM, IgG and IgA class Yersinia antibodies was studied at the beginning of an inflammatory joint disease and one year later in 354 adult patients using an ELISA technique. The control groups consisted of age and sex matched healthy persons living in the same geographical area as the patients, and of 64 patients with chronic rheumatoid arthritis. Yersinia antibodies of any Ig class were found in 9.0% of all the patients at the beginning of the disease, in 4.0% of the healthy controls and in 1.6% of the patients with chronic rheumatoid arthritis. Patients with ankylosing spondylitis, Reiter's disease or other reactive arthritis showed the highest prevalence (19.4%) of Yersinia antibodies, but in the whole material one half of the patients with Yersinia antibodies were clinically classified as rheumatoid or nonspecific arthritis. The elevated prevalence of Yersinia antibodies in patients with probable rheumatoid or nonspecific arthritis may indicate a reactive etiopathogenesis of arthritis also in some cases without previous evidence of gastrointestinal infection. Quantitation of IgG and IgA antibodies to Yersinia is important in the diagnosis of Yersinia arthritis. These antibodies may not be detected by the generally used agglutination test.

Antibodies, Bacterial↗

Absence of lymphotoxic antibodies in patients with Yersinia-induced arthritis, Reiter's syndrome and ankylosing spondylitis.

Serum samples from patients with Reiter's syndrome, ankylosing spondylitis, Yersinia-induced arthritis and Yersinia infections not followed by arthritis were collected and assayed for complement-dependent cytotoxicity, using a standard dye-exclusion microcytotoxicity technique. A total of eighty-nine serum samples derived from these patients were compared to those of forty control subjects, using as target cells six different cultured cell line cells and peripheral blood mononuclear cells isolated from the blood samples of four subjects. Serum samples from only five of the subjects demonstrated cytotoxicity. This did not depend on whether the target cells were HLA-B27 or not. Hence, if antilymphocytic auto-antibodies are present in these patients, they will require a different technique for their detection.

Adolescent↗

A preliminary analysis of the membrane proteins of arthritis-causing Yersinia.

The outer membrane proteins (OMP) of fifteen strains of Yersinia were separated from the inner membrane (IMP) and intracytoplasmic (ICP) proteins. The molecular composition of these fractions was then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The OMP of all fifteen strains exhibited a uniform pattern markedly distinct from the IMP and ICP. There was, however, heterogeneity in the OMP among the various bacteria, based on the apparent molecular weights of several of the major proteins. The two most prominent major proteins are easily distinguished because their apparent molecular weights varied substantially depending on the temperature at which the membranes were solubilized. Using the apparent molecular weights of these two proteins as a basis for comparison, the Yersinia organisms of serotype 3 presented a unique electrophoretic pattern, different from those of non-serotype 3 Yersinia organisms. Four of the nine serotype 3 organisms analyzed here were isolated from patients who developed arthritis subsequent to infection. However, no obviously unique features could be distinguished. A major focus of research effort is currently being devoted to the examination of the immune response generated against the Yersinia organisms by patients with Yersinia-induced arthritis. Most of the studies, so far, have utilized whole bacteria as the antigens. The data presented in this paper provide the basis of future analysis of such immune responses to individual molecules of Yersinia.

Arthritis↗

Electron microscopy and immunolabeling of Yersinia antigens in human synovial fluid cells.

Recent findings have emphasized the involvement of bacterial antigens in synovitis in reactive arthritis. It is still unclear, however, in what form the microbial material exists in the joint. Both antigen-containing cells and intact bacteria have been proposed as candidates on the basis of immunohistochemical studies of the synovial membrane. This study addresses that question by electron microscopy and peroxidase immunolabeling of synovial fluid cells from three patients with reactive arthritis triggered by Yersinia enterocolitica O:3. For all three patients a diffuse reaction in the cytoplasm of phagocytes was interpreted as bacterial material in a degraded form. These results are consistent with our proposal that intact bacteria rarely, if ever, enter the joints of Yersinia-triggered reactive arthritis patients.

Adolescent↗

Effect of antimicrobial treatment on chronic reactive arthritis.

In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated. At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group. We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established.

Adult↗