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H E Jasin

Publications and source records attributed to H E Jasin.

18 recordsLinked to original sources
PubMed1992

Interactions between anticollagen antibodies and chondrocytes.

OBJECTIVE: To investigate the interactions between anticollagen antibodies and living chondrocytes. METHODS: Mouse monoclonal anti-type II collagen (anti-CII) antibodies, rabbit anti-human CII, and rat anti-CII, anti-CIV, anti-CV, anti-CVI, and anti-CIX were studied in vitro to determine their ability to bind to the plasma membrane of living bovine chondrocytes. RESULTS: Mouse monoclonal anti-CII, rabbit anti-CII, and rat anti-CII, anti-CV, and anti-CIX were shown to bind in vitro to the plasma membrane of bovine chondrocytes. Antibody binding was not observed with anti-CIV, or with chondrocytes previously incubated with bacterial collagenase. A significant increase in chondrocyte caseinase and collagenase secretion was observed following sequential incubation with the monoclonal antibodies and a source of activating cytokines. CONCLUSION: These results suggest that collagen autoantibodies may exert some of their pathogenic effects on cartilage through interactions with resident chondrocytes, leading to modulation of the rate of secretion of cartilage matrix-degrading enzymes.

Animals↗
PubMed1992

Amelioration of antigen-induced arthritis in rabbits treated with monoclonal antibodies to leukocyte adhesion molecules.

OBJECTIVE: To examine the effects of treatment of antigen-induced arthritis in rabbits with a monoclonal antibody against CD18, the common beta chain of the leukocyte adhesion molecules. Intraarticular injection of antigen into primed rabbits elicits an acute inflammatory response followed by chronic arthritis in this model. METHODS: Anti-CD18 was given at the time of intraarticular antigen administration, and effects on the acute and chronic arthritis were investigated. Twenty-four rabbits were examined (11 controls, 3 receiving normal mouse IgG, and 10 receiving anti-CD18). RESULTS: Flow cytometry of blood leukocytes at anti-CD18 administration showed saturating amounts of mouse Ig coating all the circulating cells. Treatment effects on the acute arthritis (measured by quantitating the synovial cell exudate 24 hours after arthritis induction) were a profound reduction in the number of inflammatory cells and a striking decrease in the proportion of polymorphonuclear leukocytes recovered from the synovial cavity, indicating a decrease in acute inflammation. Treatment effects on the chronic synovitis (2 and 4 weeks later) compared with controls showed a significant decrease in synovial fluid cell counts at 2 weeks (1.7 versus 21.0 x 10(6)/joint, P less than 0.03) and at 4 weeks (7.4 versus 22.6 x 10(6)/joint, P less than 0.05). Histologic evaluation of the synovium (0-3+ scale, scored "blindly") of anti-CD18-treated rabbits and controls showed marked decreases in subsynovial cell infiltration and lymphoid follicle formation both at 2 weeks (1.0 versus 2.25, P less than 0.005; and 0 versus 1.75, P less than 0.001) and at 4 weeks (1.48 versus 2.17, P less than 0.01; and 0.75 versus 2.08, P less than 0.02). Quantitation of cartilage-bound immune complexes, and of synovial synthesis of Ig and specific antibody showed no differences between groups. CONCLUSION: These findings indicate that treatment with monoclonal antibody to CD18 not only modifies the initial acute arthritis, but also results in significant amelioration of the subsequent chronic inflammation in this animal model of rheumatoid arthritis.

Animals↗
PubMed1992

Interactions of synovial fluid immunoglobulins with chondrocytes.

OBJECTIVE: To study the interaction of synovial fluid (SF) immunoglobulins with living chondrocytes, and to evaluate the relative contribution of type II collagen (CII) antibodies. METHODS: SF of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and gout were incubated with isolated bovine articular chondrocytes. Ig binding was measured by flow cytometry and by quantitation with 125I-labeled anti-IgG and anti-IgM. Complement-dependent cytotoxicity was determined by 51Cr release. Immunoglobulin binding and cytotoxicity were compared between chondrocytes obtained from the superficial and from the deep cartilage zones. RESULTS: Significantly greater IgG and IgM binding was found with RA SF compared with OA or gout SF. Chondrocytes bound more Ig than did fibroblasts. The relative contribution of anti-CII antibodies to Ig binding was studied following absorption of the SF with bovine CII, and by incubation with bacterial collagenase-treated chondrocytes. There was a small but significant reduction in IgG and IgM binding with SF samples that were positive for anti-CII. RA SF exhibited modest, but significantly greater complement-dependent cytotoxicity than OA SF: Gel chromatography fractionation indicated that IgM antibodies were responsible for the cytotoxic activity. Additional studies showed that SF IgM antibodies bound preferentially to, and killed chondrocytes obtained from, the superficial layers of cartilage. CONCLUSION: Anti-CII antibodies contained in RA SF represent one of many antibody specificities reacting with chondrocyte membrane antigens. Chondrocyte-reactive SF antibodies may play an important pathogenic role in the processes leading to irreversible cartilage damage in RA. These deleterious effects appear to be exerted particularly on chondrocytes located near the articular surface of cartilage.

Animals↗
PubMed1991

The relationship between circulating CD5+ B lymphocytes and in vitro autoantibody synthesis in normal individuals.

Recent observations suggest that a subpopulation of B lymphocytes bearing the phenotype CD5+ may be enriched for cells committed to the synthesis and secretion of autoantibodies. We had previously shown that a subset of normal individuals has an expanded subpopulation of B lymphocytes committed to the synthesis of IgM and IgM-rheumatoid factor (RF), and that this condition was associated with HLA-DR4 (4). In these studies, we performed simultaneous quantitation of the size of the circulating CD5+ B lymphocyte subpopulation in a group of 20 normal donors, and of the pokeweed mitogen-induced in vitro synthesis of a panel of autoantibodies by the same peripheral blood cells depleted of CD8+ suppressor lymphocytes in 18 of the 20 individuals. The culture supernatants were assayed for total IgM and IgG, RF, IgM, and IgG anti-single-stranded DNA, anti-human thyroglobulin, and anti-tetanus toxoid. The mean percentage CD5+ B cells was 13.5 +/- 2.5%. There was no significant correlation between total B lymphocytes and CD5+ B cells (R = 0.25, P greater than 0.20. Positive correlations were found between the proportion of circulating CD5+ B lymphocytes and synthesis of RF (R = 0.73, P less than 0.001), and IgM anti-DNA (R = 0.58, P less than 0.03). Significant correlations were not found between CD5+ B cells and secreted IgM or IgG antibodies against the exogenous antigen tetanus toxoid, measured in the same supernatants. The antibodies produced in vitro by T cell-dependent B cell activation appear to have limited or no polyspecificity. These results indicate that the size of the circulating CD5+ B cell subpopulation in any given individual contributes importantly to the magnitude of autoantibody synthesis in cultures where T cell-mediated B lymphocyte activation takes place in the absence of suppressor signals.

Antigens, CD↗
PubMed1991

Mechanisms of disruption of the articular cartilage surface in inflammation. Neutrophil elastase increases availability of collagen type II epitopes for binding with antibody on the surface of articular cartilage.

We recently observed that specific antibodies to type II collagen do not bind in appreciable amounts to the intact surface of articular cartilage, whereas antibodies to the minor collagen types V, VI, and IX do. These results suggest that the outermost cartilage surface layer prevented interaction of the antibodies with the major collagen type in articular cartilage. The present studies were designed to investigate the pathogenic mechanisms involved in the disruption of the cartilage surface layer in inflammatory arthritis. Articular cartilage obtained from rabbits undergoing acute antigen-induced arthritis of 72 h duration showed a significant increase in binding of anti-type II antibody to cartilage surfaces compared with normal control cartilage (P less than 0.01). Augmentation of anti-type II binding was also observed upon in vitro incubation of bovine articular slices or intact rabbit patellar cartilage for 1 h with human polymorphonuclear neutrophils (PMN), PMN lysates, or purified human PMN elastase. This increase was not inhibited by sodium azide, nor was it enhanced by incubation of cartilage with the strong oxidant hypochlorous acid. Chondrocyte-mediated matrix proteoglycan degradation in cartilage explants cultured in the presence of cytokines failed to increase antibody binding appreciably. The augmentation in antibody binding seen with PMN lysates was inhibited by the nonspecific serine-esterase inhibitor PMSF, but not by the divalent metal chelator EDTA. The elastase-specific inhibitor AAPVCMK also inhibited most of the PMN-induced increase in antibody binding, whereas the cathepsin G-specific inhibitor GLPCMK was much less effective. Incubation of intact cartilage with purified human PMN elastase indicated that this serine esterase could account for the increase in anti-type II collagen antibody binding to intact cartilage surfaces. These studies suggest that in an inflammatory response, PMN-derived elastase degrades the outer layer of articular cartilage, exposing epitopes on type II collagen. They also help clarify the pathogenic mechanisms involved in early articular cartilage damage in inflammatory joint diseases.

Animals↗
PubMed1979

Interaction of polymorphonuclear leukocytes with immune complexes trapped in joint collagenous tissues.

The present experiments were designed to investigate in vitro interactions between polymorphonuclear leukocytes (PMN) and rabbit joint collagenous tissues containing trapped immune complexes. Articular cartilages and menisci from antigen-injected and control joints were incubated with normal PMN isolated from rabbit peritoneal exudates or blood. After incubation of cartilage and menisci from antigen-injected joints with PMN, large numbers of PMN became attached to the articular surface. In areas of superficial erosion, the PMN invaded the tissue several cell diameters below the articular surface. Through immunoelectron microscopy, degranulated PMN were observed in scattered areas to phagocytose amorphous material containing rabbit Ig. Following addition of PMN to control tissues, only a few PMN became attached to the articular surface. When tissues from monosodium urate-injected joints were incubated with PMN, these cells were found attached to the surface in moderate numbers, but invasion into the tissues was not seen. These studies indicate that immune complexes trapped in joint collagenous tissues may lead to enhanced release of lysosomal hydrolases.

Animals↗
PubMed1979

Increased C1q binding immune complexes in Felty's syndrome: comparison with uncomplicated rheumatoid arthritis.

Sera from patients with Felty's syndrome (FS) and rheumatoid arthritis (RA) were examined for the presence of circulating immune complexes (IC) by using the 125I-C1q binding and monoclonal rheumatoid factor (mRF) techniques. Of 15 patients with FS, 9 (60%) had high 125I-C1q binding as compared to 3 of 26 RA patients (12%). The average C1q binding was significantly higher in the FS patients than in the RA patients without FS. C1q binding in both FS and RA patients was significantly higher than a group of 90 normal controls. In addition, serum C4 levels were significantly lower in the FS patients than in the RA patients. In contrast to these findings, IC levels in FS and RA patients were very similar when measured by the mRF technique. These studies indicate that FS patients have higher levels of complement-fixing IC in their sera than RA patients without FS. These findings raise the possibility that the complement-fixing IC found in these patients may play a role in the pathogenesis of neutropenia of FS.

Adult↗
PubMed1979

Protein synthesis and secretion by activated human lymphocytes.

Human peripheral blood mononuclear cells showed increased synthesis and secretion of protein in response to stimulation by mitogens. Protein secretion in response to concanavalin A (Con A) correlated with cellular proliferation and originated from the proliferating cells. Selective depletion of either B lymphocytes or monocytes did not lead to a reduction in the total protein secreted, suggesting that the T lymphocyte was the cell contributing most of the synthetic activity. It is concluded that the measurement of newly synthesized and secreted protein by Con A activated mononuclear cells is a measurement of the T-lymphocyte response.

Agammaglobulinemia↗
PubMed1978

The inflammatory role of immune complexes trapped in joint collagenous tissues.

The inflammatory role of immune complexes trapped in joint collagenous tissues has been investigated. Joint collagenous tissues obtained from rabbits with antigen-induced arthritis generated mediators of acute inflammation when incubated with fresh normal rabbit serum as a source of complement. The role of trapped immune complexes in chronic inflammation was also studied by the surgical insertion of menisci, obtained from arthritic and control joints, into the suprapatellar pouches of previously immunized or naive recipient animals. It was shown that when immune complex containing menisci were inserted into immune rabbits, a chronic inflammatory capsule developed around the donor tissue, reminiscent of the inflammatory pannus seen in rheumatoid cartilage. Normal menisci and immune complex containing menisci inserted in naive animals developed capsules rich in fibroplasts and collagen fibres. Since we have previously shown the presence of immune complexes in the great majority of joint collagenous tissues obtained from patients with rheumatoid arthritis, our results suggest that these complexes may play a role in the formation of pannus, which constitutes a major mechanism responsible for cartilage destruction.

Animals↗
PubMed1977

Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus.

Normal peripheral blood mononuclear cells demonstrated increased DNA synthesis and secretion of newly synthesized protein when suboptimal concentrations of Concanavalin A (Con A) were added to the cultures after 24-h incubation in vitro. Cells stimulated by Con A, 1 mug/ml, after 24-h incubation demonstrated 3.0 times more tritiated thymidine incorporation, and 4.4 times more 14C-amino acid incorporation into newly synthesized secreted protein, than cells stimulated at 0 h (P less than 0.001). The acquisition of increased responsiveness was not abrogated by washing and resuspending the cells in fresh medium. Since the increased responsiveness could be inhibited by the addition to the cultures of small numbers of cells previously activated by Con A it is suggested that the enhanced reactivity acquired in culture represents the loss of a subpopulation of suppressor cells that modulate the T-lymphocyte response. Cells from nine patients with active, untreated systemic lupus erythematosus demonstrated normal responses to optimal concentrations of Con A added at 0 h, but an impaired response to Con A, 1 mug/ml. When these cells were incubated for 24 h, a significant increased response to Con A was not observed. This observation suggests that patients with active SLE lack circulating suppressor cells. When seven SLE patients were again studied after corticosteroid therapy had led to clinical improvement, the response to Con A, 1 mug/ml, added after 24-h incubation was similar to that observed in normal controls, suggesting that suppressor function in SLE returns as disease activity declines.

Adolescent↗
PubMed1977

Absence of the eighth component of complement in association with systemic lupus erythematosus-like disease.

A 56-yr-old black woman with absence of the eighth component of complement and a disease compatible with systemic lupus erythematosus is described. Her disease is characterized by the presence of photosensitive "malar" rash, alopecia, polyarthritis, and nephrotic syndrome. Hemolytic and immunochemical assays of the serum complement components were normal, except for C8 which was undetectable. Hemolytic activity could be restored to normal by the addition of functionally pure C8. In vitro tests to investigate the functional integrity of the classical and alternative pathways indicated that the functions mediated by activation of C3 and C5 were intact whereas heatlabile bactericidal activity was totally absent. Addition of C8 restored this function to normal levels. One of two brothers of the proband was shown to have serum C8 levels approaching 50% of normal indicating the hereditary nature of the defect. HLA typing studies showed that the normal brother had identical haplotypes to the proband while the proposed heterozygous brother only shared one haplotype with the patient, suggesting that the gene controlling the C8 defect was not closely linked to the major histocompatibility complex. If the association of a connective tissue disease and absence of a terminal component of complement is not coincidental, these results suggest that C8 deficiency may be associated with a subtle defect in the defense mechanisms to viral infection leading to viral persistance and perhaps to diseases such as systemic lupus erythematosus where chronic viral infections have been implicated.

Complement C8↗
PubMed1975

The mechanism of trapping of immune complexes in experimental antigen-induced arthritis.

The role of acute inflammation and of specific antibody in the retention of antigen in joint collagenous tissues of immunized rabbits was examined. The role of the acute synovitis occurring immediately after IA antigen injection in the retention of immune complexes was investigated by the concomitant IA injection of trace amounts of 1258-BSA and mono-sodium urate crystals and by the production of an acute Arthus reaction using an unrelated antigen in doubly immunized rabbits. In neither case was more 125I-BSA retained in the inflamed joint tissues compared to the contralateral noninflamed joints 7 days after antigen injection. In addition, immunized rabbits depleted of ciruclating polymorphonuclear leukocytes by previous treatment with nitrogen mustard retained 2.7 times more antigen than control, nonimmune animals. In another experiment, antigen retention in joint collagenous tissues was greatest 30 min after IA injection, before the appearance of acute inflammatory synovitis. These findings suggest that acute inflammation is not a major factor in the retention of antigen in collagenous tissues. To investigate the role of antibody in the retention of antigen, nonimmune rabbits were injected i.v. with purified anti-BSA antibody three days prior to the intraarticular injection of BSA. Over 20 times more antigen was retained irreversibly in collagenous tissues obtained from the injected joints of passively immunized animals as compared to similar tissues of control rabbits. When rabbits were injected i.v. with purified anti-BSA antibody and either killed 20 min or 3 days later, in vitro binding of antigen by joint collagenous tissues was seen only in animals where antibody was allowed to equilibrate with the extravascular space for 3 days. These findings indicate that retention of antigen depends on the presence of extravascular antibody. It is concluded that the trapping of immune complexes in collagenous joint tissues of immunized animals depends on: (1) the presence of antibody in the extravascular space; (2) the diffusion of antigen or soluble complexes into this space; (3) the interaction of antigen or soluble complexes with extravascular antibody with subsequent formation of larger and more insoluble complexes, and (4) the trapping of these complexes in the collagen fiber meshwork.

Animals↗
PubMed1975

Mechanism of trapping of immune complexes in joint collagenous tissues.

The role of acute inflammation and of pre-existing specific antibody in the retention of intra-articular antigen in joint collagenous tissues of immunized rabbits was examined. The role of the acute synovitis occurring immediately after antigen injection was investigated by the production of acute synovitis in immune and non-immune rabbits. In no case was more 125I-labelled BSA retained in the inflamed joint tissues compared to the contralateral non-inflamed joints 7 days after intrarticular antigen injection. When antigen retention was examined early after intra-articular injection, the largest amount of antigen was retained 30 min after injection, before the appearance of the acute inflammatory synovitis. These findings suggest that acute inflammation does not constitute a major factor in the long-term retention of antigen in collagenous tissues. To investigate the role of antibody in the retention of antigen, non-immune rabbits were injected intravenously with purified anti-BSA antibody 3 days prior to the intra-articular injection of BSA. Over 20 times more antigen was retained irreversibly in collagenous tissues obtained from the injected joints of passively immunized animals compared with similar tissues of control rabbits. When rabbits were injected intravenously with purified anti-BSA antibody and either killed 20 mins or 3 days later, in vitro binding of antigen by joint collagenous tissues was seen only in animals where antibody was allowed to equilibrate with the extravascular space for 3 days. These findings indicate that retention of antigen depends on the presence of extravascular antibody. Antigen retention in collagenous tissues was also present when both antibody and antigen were injected intravenously and antibody was given 3 days before the antigen. It is concluded that the trapping of immune complexes in collagenous joint tissues of immunized animals depends on: the presence of antibody in the extra-vascular space; the diffusion of antigen or soluble complexes into this space; the interaction of antigen or soluble complexes with extravascular antibody with subsequent formation of larger and more insoluble complexes; and the trapping of these complexes within the collagen fibre meshwork.

Animals↗
PubMedDate not supplied

Immunoglobulin synthesis by peripheral blood cells in systemic lupus erythematosus.

A study of the immunoglobulin (Ig) synthesis by peripheral blood cells of patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and controls was carried out. Synthesis was markedly elevated in patients with active SLE, whereas patients with the active SLE or RA showed normal values. Treatment of 3 patients with active SLE resulted in a reduction of Ig synthesis that correlated well with the disappearance of disease activity. There results indicate that the abnormal immune process in active SLE, characterized by intense B-lymphocyte stimulation, is associated with the appearance of more highly differentiated B cells in the blood.

Antibodies, Antinuclear↗
PubMedDate not supplied

Identification of immunoglobulins and complement in rheumatoid articular collagenous tissues.

Ninety-three patients with a variety of joint diseases were studied for evidence of immune complexes in articular collagenous tissues. Frozen sections of freshly obtained biopsies of hyaline articular cartilage and menisci were stained with fluoresceinated monospecific antisera for evidence of human immunoglobulins (IgG, IgM,IgA) and the beta1c component of complement. The criterion for the presence of complexes was the staining of two or more immunoglobulins and beta1c in an identical location of sequentially cut sections. Of the 42 patients with rheumatoid arthritis (RA) 83% were positive by this criterion. In those with classic RA the incidence was 92%. Sixteen patients with fresh joint trauma or nonarthritic disease had negative findings. Among 26 patients with noninflammatory disease, 4 of 8 with polyarthritis whose features suggested primary degeneration, 1 of 11 patients with secondary degenerative arthritis, and a single case of synovial osteochondromatosis had positive findings. Among 9 patients with miscellaneous inflammatory arthritides, all of 3 with psoriatic arthritis were negative; however 2 of 6 with other inflammatory arthritides were positive. The findings in classic RA suggest that immune complexes are deposited in the articular collagenous tissues. The persistence of these complexes may play a significant role in the chronicity of the synovitis.

Adolescent↗
PubMedDate not supplied

Systemic lupus erythematosus, partial lipodystrophy and hypocomplementemia.

A patient with partial lipodystrophy, increased susceptibility to infection and a clinical picture compatible with systemic lupus erythematosus is described. This patient had persistently low serum C3 levels and a C3-cleaving factor similar to the C3 nephritic factor (C3NeF). During periods of disease inactivity, serum levels of the other components of the classical and alternative pathways of complement measured were normal; heat labile opsonic capacity was low, suggesting functional depletion of factors of the alternative pathway of complement activation.

Adult↗