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Biomedical subjects

K Fehr

Publications and source records attributed to K Fehr.

At least 55 records · Page 3Linked to original sources
PubMed1976

Experimental arthritis of rabbits caused by intra-articular injection of autologous Fab2 produced by digestion of IgG with cathepsin D.

Intra-articularly injected autologous Fab2 produced from IgG by homologous cathepsin D induces in animals not given prior immunization acute synovitis after 1 and 3 injections, acute synovitis after 6 injections, and chronic synovitis after 12 injections. Histologically, the chronic synovitis is similar to synovitis in rheumatoid arthritis (RA). In the joint, cathepsin D Fab2 appears to act as a fairly strong antigen. Evidence for this is provided by the infiltration of large numbers of polymorphonuclear leucocytes, the marked phagocytic activity of the exudate leucocytes and tissue phagocytes, and the stimulation of the synthesis of specific antibodies (homoreactants) in the synovial plasma cells. The immediate action of injected Fab2 suggests that it forms biologically active immune complexes with homoreactants already present. These complexes are phagocytosed, the homoreactants being demonstrable immunohistochemically in inclusions of the exudate and tissue phagocytes. In addition, the local synthesis of antigammaglobulins of rheumatoid factor type is also induced. These react with heat-aggregated homologous as well as human IgG and are likewise found in inclusions in the exudate and tissue phagocytes. In the serum of the animals the titre of rheumatoid factor-like antigammaglobulins increases to an extent depending on the number of injections given. These histochemical and serological findings show striking parallels with the findings in human RA.

Acute Disease↗
PubMed1976

Circulating and intra-articular immune complexes in patients with rheumatoid arthritis. Correlation of 125I-Clq binding activity with clinical and biological features of the disease.

The correlation between the incidence and level of immune complexes in serum and synovial fluid and the various clinical and biological manifestations of rheumatoid arthritis has been studied. Immune complexes were quantitated using a sensitive radioimmunoassay, the 125I-Clq binding test, in unheated native sera and synovial fluids from 50 patients with seropositive (RA +) and 45 with seronegative (RA -) rheumatoid arthritis, 17 with other inflammatory arthritis, and 37 with degenerative and post-traumatic joint disease. The following observations were made: (a) when compared to the results from patients with degenerative and post-traumatic joint diseases, the 125I-Clq binding activity (Clq-BA) in synovial fluid was found to be increased (by more than 2 SD) in most of the patients with RA + (80%) and RA - (71%) and in 29% of patients with other inflammatory arthritis; the serum Clq-BA was also frequently increased in both RA + (76%) and RA - (49%) patients, but only exceptionally in patients with other inflammatory arthritis (6%); (b) a significant negative correlation existed between the Clq-BA and the immunochemical C4 level in synovial fluids from patients with RA + and RA -; (c) neither the serum nor the synovial fluid Clq-BA in rheumatoid arthritis significantly correlated with the erythrocyte sedimentation rate, the clinical stage of the disease, or the IgM rheumatoid factor titer; and (d) the serum Clq-BA in patients with rheumatoid arthritis and extra-articular disease manifestations (40 +/- 34% in those with RA +,32 +/- 29% in those with RA -) was significantly increased as compared to the serum Clq-BA in patients with joint disease alone (24 +/- 30% in those with RA +, 10 +/- 13% in those with RA -). Experimental studies were carried out in order to characterize the Clq binding material in rheumatoid arthritis. This material had properties similar to immune complexes: it sedimented in a high molecular weight range on sucrose density gradients (10-30S) and lost the ability to bind Clq after reduction and alkylation, or after acid dissociation at pH 3.8, or after passage through an anti-IgG immunoabsorbant. DNase did not affect the Clq BA. These results support the hypothesis that circulating as well as intra-articular immune complexes may play an important role in some pathogenetic aspects of rheumatoid arthritis. The 125I-Clq binding test may also be of some practical clinical value in detecting patients who have a higher risk of developing vasculitis.

Adult↗
PubMed1976

Ultrastructural studies of rabbit synovitis induced by autologous IgG fragments. I. Proliferation of the lining cells.

The synovial lining cells of rabbits with experimental synovitis induced by intra-articular injection of cathepsin D-digested autologous IgG fragments (Fab2) have been subjected to electronmicroscopic study. From 3 to 50 such injections resulted in hyperplasia of the lining layer with an increase in the numbers of phagocytic and synthetic cells. Morphologically the phagocytes were classified into monocyte-like cells, mature and immature phagocytes, and epitheloid=like cells, indicating that synovial M cells may originate from blood monocytes that differentiate in situ like the monocytes in other tissues. The finding of "undifferentiated" (mesenchymal), transitional and mature synthetic cells in the lining layer suggests that synovial F cells are derived from the undifferentiated mesenchymal cells persisting in the synovial membrane in postnatal life. In the animals with synovitis, the synthetic cells were found to undergo mitosis but not the phagocytic cells. It is concluded that the hyperplasia of the lining layer is due to two distinct processes, namely invasion by precursors of M cells (monocytes) and local proliferation of F cells. As far as immune reactions involved in the synovitis are concerned, the possible roles played by lysosomal substances in these two processes are also discussed.

Animals↗
PubMed1976

Ultrastructural studies of rabbit synovitis induced by autologous IgG fragments. II. Infiltrating cells in the sublining layer.

The synovial sublining layer of rabbits with synovitis induced by intra-articular injection of cathepsin D digested autologous IgG fragments (Fab2) has been examined under the electron microscope. Twelve or more injections of autologous Fab2 led to chronic synovitis with dense mononuclear cell infiltrates containing lymphocytes, blastic cells, plasma cells and macrophages. In the infiltrates there was evidence that the lymphocytes had been activated prior to transformation into mature plasma cells. Indirect evidence suggests that T lymphocyte activation also occurred in these infiltrates. Cellular contacts between macrophages and lymphocytes or plasma cells as well as between M cells and lymphocytes were demonstrated. These contacts are tentatively interpreted as a feature of ongoing immune processes in the synovium.

Animals↗
PubMed1976

Experimental arthritis of rabbits caused by intra-articular injection of autologous Fab2 produced by digestion of IgG with cathepsin D. II. Microscopical and immunohistochemical findings in long-term experiments.

Over 20 successive intra-articular injections of autologous or homologous cathepsin D-Fab2 produce chronic destructive arthritis marked by dense round-cell infiltration, epitheloid hyperplasia of the lining layer, lymph nodules and a few germinal centres. 75% of the animals become Rf-positive and develop high titers of homoreactants to cathepsin D-Fab. Both these antibodies are synthesized in the synovial membrane and phagocytosed. Careful study of control animals makes it possible to exclude the possibility that the effects observed are due to the repeated joint traumata, to endo- or exotoxin-like substances, to chromatographed lysosomal material or to traces of cathepsin D. Autologous and homologous Fab2 have largely identical effects, while those of homologous or autologous IgG are much less marked. These comparisons suggest that the cathepsin D site of IgG acts as a strong antigen when exposed in the joint. The synovitis thereby induced has a pronounced tendency to spread to the left knee joint which was injected with physiological saline.

Animals↗
PubMed1976

Experimental production of rheumatoid factor-like antibodies and antibodies against the cathepsin D site of IgG following the injection of autologous Fab2.

In a very high proportion of rabbits, repeated intra- or extra-articular injections of autolous Fab2 produced by homologous cathepsin D induce the formation of Rf-like antibodies reacting with both homologous and human IgG. Moreover, intra-articular injections of this kind cause a significant rise in the titre of thm of all the animals so far tested. Rf-like antibodies against human IgG appear earlier and have higher serum titres than those reacting with homologous IgG. The reason for this latter observation seems to be the blocking of the anti-rabbit IgG antibodies by the animal's own IgG. The anti-rabbit IgG antibodies can be absorbed only on aggregated rabbit IgG. The anti-human IgG antibodies cross-react to some extent with rabbit IgG. The results of inhibition studies suggest that the formation of anti-Fab2 homoreactants is directly stimulated by the injected Fab2, whereas the Rf-like antibodies owe their appearance to immune complexes formed in vivo by the injected Fab2 and the naturally occuring anti-Fab2 homoreactants. In respect of immunoglobulin class, the two kinds of Rf-like antibody are possibly of both IgM and IgG type.

Animals↗
PubMed1975

Complement activation in seropositive and seronegative rheumatoid arthritis. 125I-C1q binding capacity and complement breakdown products in serum and synovial fluid.

1. The detection and quantitation of immune complex-like material in synovial fluid and in serum from patients with joint diseases was done through the measurement of the capacity to bind radiolabeled C1q. It was found that 65% of synovial fluid samples from seropositive or seronegative RA patients had a high C1q binding capacity as compared to other joint diseases. Immune complex-like material was also detected in 63% of serum samples from seropositive RA patients. 2. The existence of C3 or C3PA breakdown products in synovial fluid from most of the synovial fluids from RA patients probably reflects an activation of the complement system occurring in both forms of the disease. C3PA breakdown products were never found in degenerative or post-traumatic joint diseases and only occasionally in other inflammatory arthritis. Apart from their pathogenic significance, these results may have some interest for the clinical investigation of patients with joint diseases.

Arthritis, Rheumatoid↗