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Biomedical subjects

M C Boissier

Publications and source records attributed to M C Boissier.

At least 19 recordsLinked to original sources
PubMed1995

Biphasic effect of interferon-gamma in murine collagen-induced arthritis.

Interferon-gamma (IFN-gamma) exerts both enhancing and suppressing influences on collagen-induced arthritis (CIA), depending on the route and protocol of administration. To study the role of IFN-gamma on the autoimmune process of CIA, we treated DBA/1 mice with two different rat monoclonal antibodies (mAb) to murine IFN-gamma. Treatments, given twice weekly for 4 weeks, consisted of intraperitoneal injections of either mAb. In early treatments, starting from the day of immunization with type II collagen (CII), the severity of arthritis was reduced in both groups of anti-IFN-gamma-treated mice compared with control groups. Moreover, anti-CII antibody levels decreased in the sera of these mice. CIA was also down-regulated in mice treated from days 14 or 28 post immunization. In contrast, late treatments with anti-IFN-gamma mAb either induced aggravating effects, or did not affect the course of the disease. On the other hand, administration of high doses (8 x 10(4) U three times/week) of rat recombinant IFN-gamma exerted a transient increase of CIA severity. These findings suggest that IFN-gamma may play a critical role during both the induction and the course of CIA, first enhancing the immune response, and then regulating the arthritis process.

Animals↗
PubMed1994

[Clinical pitfalls in the diagnosis of microcrystalline arthritis].

Diagnosis of microcrystalline arthritis often is based on joint punctures, performed whenever possible. The clinical features of the crises may suggest diagnosis, but is not decisive. The course before or during treatment is not indicative and cannot fully exclude infection when the patient is seen during a crisis; arthritis with one or several microcrystals is possible, as in forms associated with joint infection. For well-oriented management, good knowledge of such diagnostic difficulties is necessary.

Arthritis↗
PubMed1994

[Rheumatoid polyarthritis. Immunopathological mechanisms, contribution of experimental arthritis].

Rheumatoid arthritis is an auto-immune disease the autoantigen of which has not yet been identified. Induction and maintenance of the disease may involve environmental factors (bacteria, viruses) and autoantigens directly issued from the articular tissue (collagens, proteoglycans). T cells play a crucial role in rheumatoid arthritis; after the antigen has been recognized, they secrete lymphokines and enable other T and B lymphocytes to be activated. The synovial cells themselves can produce large amounts of lymphokines and enzymes which contribute to the destruction of joints. The immunopathology of rheumatoid arthritis is now much better known owing to studies of experimental arthritis which are the animal models of the disease. These models have helped in validating therapeutic approaches based on immunointervention.

Animals↗
PubMed1994

T cell regulation of collagen-induced arthritis in mice. III. Is T cell vaccination a valuable therapy?

Since T cells play a critical role in collagen-induced arthritis (CIA), CD4+ T cell hybridomas were derived from DBA/1 mice immunized with bovine type II collagen (CII). The hybrid clones selected were Thy-1-2+, CD4+, CD8-, T cell receptor (TcR) alpha beta + and produced interleukin-2 in response to CII peptides presented by I-Aq molecules. The clones were collagen type-specific and recognized CII from many species except the mouse. More precisely, the reactivity was directed against the immunodominant cyanogen bromide-cleaved fragment CB11(II). Analysis of the TcR carried by the T cell hybridomas showed that they used identical V alpha and J alpha (V alpha BMB, J alpha 20) gene segments and two distinct V beta (V beta 1 and V beta 4) associated with the J beta 2.5 gene segment. Interestingly, the junctional regions were highly conserved in structure and length. These findings may indicate a strong in vivo selection by the antigen for a particular combination of both alpha and beta chains of the TcR. Inoculation of irradiated anti-CII T cell hybrids into DBA/1 mice, before priming with CII, altered the course of the disease resulting in either a long-lasting suppression or an exacerbation of CIA whereas a control CD4+ hybridoma with an unrelated specificity did not influence the development of arthritis. However, the regulatory effect of anti-CII T cell clones was unpredictable, suggesting that the TcR structure may not solely account for the modulation of CIA and that T cell vaccination is not a reliable method for inducing suppression of CIA.

Amino Acid Sequence↗
PubMed1994

A peripheral protein associated with the cis-Golgi network redistributes in the intermediate compartment upon brefeldin A treatment.

Human autoantibodies offer unique tools for the study of cellular constituents since they usually recognize highly conserved components, the most difficult to detect due to their low immunogenicity. The serum from a patient with Sjögren's syndrome (RM serum) showing a very high reactivity to the Golgi complex has been shown to immunoprecipitate and to immunodetect by Western blotting experiments a protein mol wt 210,000 (p210) that was shown to be peripheral and cytoplasmically disposed. A close examination of the p210 labeling revealed some differences with Golgi markers: RM serum staining was slightly more extensive than several Golgi markers and showed a discontinuous or granular appearance. Nocodazole induced a specific and early segregation of many p210-associated vesicles or tubules from Golgi apparatus. Upon brefeldin A treatment, p210 did not redistribute in the ER as did other Golgi proteins. In contrast, it exhibited a vesicular pattern reminiscent to that displayed by proteins residing in the intermediate compartment. Double staining immunofluorescence using the RM serum and the marker of the intermediate compartment, p58, revealed segregation of both proteins in control conditions but colocalization in BFA-treated cells. We have further demonstrated by combining different drug treatments that p210-containing elements in brefeldin A-treated cells belong indeed to the intermediate compartment. Experiments on brefeldin A recovery suggested that these p210 elements might play a role in reformation and repositioning of the Golgi apparatus. Ultrastructural localization performed by immunoperoxidase staining allowed us to establish that p210 interacted with the external side of an abundant tubulo-vesicular system on the cis side of the Golgi complex which extended to connecting structures and vesicles between saccules or stacks of cisternae, p210 appears to be a novel protein residing in the cis-Golgi network that may cycle between the Golgi apparatus and the intermediate compartment.

Autoantigens↗
PubMed1992

[Acute renal insufficiency associated with lymphoma. A new case].

We report on a case of acute renal failure secondary to relapse of a centrocytocentroblastic non-Hodgkin's lymphoma. Twenty-seven cases of acute renal failure due to lymphomatous infiltration of the kidneys have been so far reported. The clinical presentation is non-specific; the size of the kidneys appears normal or enlarged; diagnosis is confirmed by renal biopsy and/or CT scan examination. Chemotherapy and/or radiotherapy sometimes lead to dramatic improvement of renal function. However, prognosis is poor, mostly due to lymphomatous evolution.

Acute Kidney Injury↗
PubMed1992

Combination of cyclosporine A and calcitriol in the treatment of adjuvant arthritis.

We investigated combination treatment with cyclosporine A (CsA) and calcitriol (CT), 2 immunomodulatory agents, in vivo in the adjuvant arthritis (AA) model in rats. Treatment initiated at priming with complete Freund's adjuvant consisted of daily administration of CsA and CT during the prearthritic phase (14 days). CsA given alone delayed the onset of the disease, whereas the severity was either not affected or paradoxically enhanced. Injection of CT alone reduced the severity of arthritis. The association of low doses of CsA (5 mg/kg) and CT (0.2 micrograms/kg) further delayed the onset of AA and abolished the aggravating effect. Our findings suggest that low doses of CsA and CT in association exhibit the additive beneficial effects of either agent alone.

Administration, Oral↗
PubMed1991

Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific antibodies.

Immunization with native type II collagen (CII) of susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. Collagen-induced arthritis (CIA) is an experimental model for T cell-mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII-primed DBA/1 mice were treated with various TcR V beta-specific monoclonal antibodies (mAb) using a protocol resulting in a long-term elimination of the target T cells. In vivo treatment with anti-CD4 mAb led to nearly complete protection against CIA. Mice injected with anti-V beta 8.1, 2 or anti-V beta 5.1, 2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti-V beta 2 mAb delayed the onset of the disease whereas injection of anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Moreover, the combined treatment with anti-V beta 2 and anti-V beta 5 mAb efficiently reduced the development of CIA. The humoral response to CII was down-regulated only in the groups of mice that were improved by the treatment. In vitro proliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti-V beta mAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA express a limited number of V beta chains.

Animals↗
PubMed1991

[Role of collagen conformation in type II anticollagen immunity in rheumatoid polyarthritis].

Type II anticollagen (CII) autoimmunity is a frequently reported, but non-specific, phenomenon in rheumatoid arthritis (RA). The authors show that in 88 sera samples from patients suffering from RA, the incidence of antibodies targeted against endogenous human CII was the same as that found for 149 control blood donors (14.8% versus 11.4%). However, a significant difference was found for the incidence of antibodies targeted against the alpha-chains of CII (26.1% versus 6.0%, p less than 0.001). As a result of investigating the specificity of the anti-CII antibodies in greater detail by means of an immunoprinting of the CII peptide fragments obtained after splitting the molecule by cyanogen bromide, the authors have demonstrated that the largest CII peptides (CB10 and CB11) were better recognized than the smaller peptides (CB8, CB9.7), with no significant difference between PR and control plasmas. Using competitive methods, evidence was obtained in support of heterogeneous recognition by the anti-CII antibodies: some recognize conformational determinants only, whereas others are targeted against the primary sequences of the alpha-1 (II) chain.

Antibody Diversity↗
PubMed1990

T cell regulation of collagen-induced arthritis in mice. I. Isolation of Type II collagen-reactive T cell hybridomas with specific cytotoxic function.

After immunization with native type II collagen (CII), susceptible strains of mice (H-2q) develop a polyarthritis that mimics rheumatoid arthritis. Although the underlying mechanisms are still undefined, T cells and particularly CD4+ lymphocytes seem to play a crucial role in the initiation of collagen-induced arthritis. To investigate whether CD8+ cells may participate in the pathogenesis of the disease, we have generated lines and clones of cytotoxic T cell hybridomas reactive to CII by fusion of lymph node and spleen cells from bovine native CII-primed C3H.Q (H-2q) mice and the AKR-derived thymoma cell line BW 5147. Clones were selected for their ability to lyse syngeneic macrophages pulsed with bovine native CII in an Ag-dependent manner. The two hybrid clones that were characterized, exhibited cell surface phenotypes of cytotoxic cells and reacted with CII purified from various species. However, each of them recognized different determinants on the CII molecule. P3G8 clone was specific for an epitope shared by CII and type XI collagen, whereas P2D9 clone reacted with CII and type IX collagen. Both hybridomas recognized CII-pulsed targets in association with H-2Kq molecules. These data indicate that the two CII-specific cytotoxic clones recognize different epitopes that are shared by other articular collagens and will allow us to test their influence on the development of arthritis in vivo.

Animals↗
PubMed1990

Arthritogenicity of minor cartilage collagens (types IX and XI) in mice.

Native type II collagen, the major cartilage collagen, is immunogenic and arthritogenic in rodents. To investigate whether minor cartilage collagens are arthritogenic, we immunized DBA/1 mice with the pepsin-soluble fractions of type IX or type XI collagen emulsified in Freund's complete adjuvant. Both collagens were arthritogenic in DBA/1 mice after only 1 injection. However, the incidence of the polyarthritis was lower and the severity was lesser than with that induced by bovine type II collagen, even when a booster injection was administered. All mice developed a humoral response to the immunizing antigen, without any relationship to the arthritic status. Interestingly, competition experiments showed that antibodies raised against type XI collagen also bound with high avidity to type II collagen. In contrast, sera from type IX collagen-immunized mice did not react with either type II or type XI collagen. We conclude that types IX and XI minor cartilage collagens are both arthritogenic and immunogenic in DBA/1 mice. Whether the recognition of epitopes common to different collagens is relevant to the articular pathology remains to be elucidated.

Animals↗
PubMed1989

Polyarthritis in MRL-lpr/lpr mice: mouse type II collagen is antigenic but not arthritogenic.

In addition to a lupus-like syndrome and massive T cell proliferation, MRL-lpr/lpr(MRL/l) mice develop an arthritic process very similar serologically and histologically to human rheumatoid arthritis (RA). Recently, we have developed in DBA/1 mice an experimental model of autoimmune arthritis (EAA) which shares clinical features with RA, by injecting homologous type II collagen (CII). In order to investigate the possible relationship between the spontaneous polyarthritis of MRL/l mice and collagen induced EAA, we immunized MRL/l mice with mouse (M) CII. Our findings revealed that the injection of 100 micrograms M-CII in young or old MRL/l mice did not modify the articular pathology which spontaneously develops in non-injected mice. Circulating autoantibodies to native M-CII were found in the sera of immunized young mice but were not detected in non injected or immunized old mice. Conversely, denatured alpha 1 (II) chains or CB peptides derived from M-CII were recognized by most of the MRL/l sera whether mice had been immunized or not. The incidence of positive sera as well as the intensity of the response evaluated by Western blot analysis increased with the age of the mice. Taken together, our data suggest that, even if the injection of homologous CII in MRL/l mice may accelerate the onset of joint pathology, the spontaneous disease arises independently of an autoimmune response against native CII.

Animals↗