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Biomedical subjects

Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

At least 433 records · Page 24Linked to original sources
PubMed1996

Do some antiphospholipid antibodies target endothelial cells?

Anti-endothelial cell activity is partly due to antiphospholipid antibodies (aPLA) because: a) the two types of antibodies are present in patients with connective tissue diseases and cardiolipin-binding monoclonal antibodies recognize endothelial cells (EC); b) anionic phospholipids are detectable on the outer face of the EC membrane lipid bilayer and an anti-beta 2-glycoprotein I (beta 2-GPI) monoclonal antibody binds to EC; c) the binding of aPLA to EC and the functional affinity of this binding are dependent on the presence of beta 2-GPI; d) anti-EC antibodies trigger the expression of anionic phospholipids on the outer leaflet of the EC membrane.

Antibodies, Antiphospholipid↗
PubMed1996

Membranous nephropathy in primary antiphospholipid syndrome: description of a case and induction of renal injury in SCID mice.

Primary antiphospholipid syndrome (PAPS) is a recently recognized clinical entity encompassing the combination of thromboembolic phenomena, thrombocytopenia and recurrent abortions in the presence of antiphospholipid antibodies. We present a patient with PAPS accompanied by renal involvement, manifested as membranous nephropathy, as proven by a renal biopsy. To investigate further the possible association between PAPS and the renal lesions we attempted to induce similar renal manifestations by transferring peripheral blood lymphocytes (PBL) from this patient to severe combined immunodeficiency (SCID) mice. The mice transfused with PBL from the affected patient exemplified antiphospholipid antibodies (aPL) following which a renal lesion consistent with the human membranous nephropathy lesion was precipitated. This study substantiates the role of aPL as possible inducers of renal damage.

Adult↗
PubMed1996

Reactivity to tyrosinase: expression in cancer (melanoma) and autoimmunity (vitiligo).

Anti-tyrosinase antibodies are found in the sera of patients with diffuse vitiligo, metastatic melanoma and in sera of patients with melanoma and hypopigmentation (MAH). The autoantigen is tyrosinase itself, the enzyme that participates in pigment (melanin) formation by both melanocytes and melanoma cells. The production of autoantibodies in both diseases is associated with the development of white patches on the patients' skin. The presence of these autoantibodies in patients with melanoma may suggest a better prognosis. Cross-antigenicity between melanoma cells and normal melanocytes is most probably the key mechanism leading to the appearance of MAH. Anti-tyrosinase antibodies are absorbed by melanocytes and by melanoma cells in all the 3 situations (melanoma, vitiligo, MAH). However, since the production of antibodies in vitiligo exceeds that in melanoma or MAH, the antibodies are detected in significantly higher levels only in vitiligo. It is suggested here that anti-tyrosinase antibodies may be responsible, or at least participate in destruction of normal melanocytes during the immune response to melanoma antigens. This mechanism may be responsible for the phenomenon of MAH in patients with melanoma, and for the formation of the autoimmune vitiligo. Anti-tyrosinase antibodies may serve for two clinical applications. One is a marker for monitoring and follow up of patients with melanoma treated by immune therapy. The second is active (or passive) immunotherapy. We have recently shown that C57BL/6J mice immunized with tyrosinase generated a high titer of antityrosinase antibodies, and following the inoculation of melanoma cells developed lower number of lung metastases, compared to the unvaccinated control group.

Autoantibodies↗
PubMed1995

Bromocriptine immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells.

Bromocriptine (BRC) is a dopamine agonist that suppresses the secretion of prolactin by the pituitary gland and is known to have immunomodulating properties. In the present study, we investigated the effect of BRC on the development of two autoimmune experimental models: (i) systemic lupus erythematosus (SLE), induced by injection of a human anti-dsDNA monoclonal antibody (MIV-7); (ii) primary anti-phospholipid syndrome (PAPS), induced by injection of a mouse anticardiolipin monoclonal antibody (CAM). BRC had a suppressive effect on in vivo autoantibody production, as well as on the appearance of other manifestations of the respective disease. The BRC activity seems to be nonspecific, since the same effect was demonstrated in mice with lupus and with PAPS. These data were supported by the in vitro nonspecific effect of CD8 cells induced in vivo by bromocriptine, on specific lymph node cell proliferation in the presence of the pathogenic monoclonal antibodies (MIV-7 or CAM, respectively), and on the response to an irrelevant autoantigen, myelin basic protein. These data were complemented by the nonspecific suppressive effect by the T-suppressor factor, produced by the CD8 cells, on specific thymidine uptake by lymph node cells from experimental SLE or PAPS in the presence of the immunizing mAb. Injection of CD8 cells from BRC-treated mice with SLE or PAPS abolished the disease development in the lupus and PAPS experimental models. The data suggest a possible novel role of bromocriptine in downregulating autoimmune phenomena through induction of natural nonspecific CD8+ suppressor cells.

Animals↗
PubMed1995

Transfer of experimental antiphospholipid syndrome by bone marrow cell transplantation. The importance of the T cell.

OBJECTIVE: To investigate the potential of bone marrow cells from mice with primary antiphospholipid syndrome (APS) to transfer the disease to naive mice, and to determine the importance of the role of T cells in the APS. METHODS: Experimental primary APS was induced in naive mice following active immunization with anticardiolipin (aCL) monoclonal antibody (MAb). Whole-population or T cell-depleted bone marrow cells from mice with experimental primary APS were infused into total body-irradiated naive BALB/c recipients. RESULTS: Bone marrow cells (in the presence of T cells) had the potential to induce experimental APS in naive mice, which resulted in high serum titers of aCL, antiphosphatidylserine, and antiphosphatidylinositol antibodies; an increased number of antibody-forming cells specific for each of the above phospholipids; a positive lymph node cell proliferative response to aCL MAb; and clinical features of primary APS, including thrombocytopenia, prolonged activated partial thromboplastin time (indicating the presence of lupus anticoagulant), and a high frequency of fetal resorptions (the equivalent of human fetal loss). T cell-depleted bone marrow cells did not transfer the disease. CONCLUSION: This study demonstrates the important role of T cells in the development and transfer of experimental primary APS and raises the possibility of T cell manipulations in treatments to prevent this condition.

Animals↗
PubMed1995

Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice. Pathogenetic role in experimental vasculitis.

OBJECTIVE: To investigate the pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG). METHODS: BALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANCA and other autoantibodies were determined. Mouse ANCA were tested for their ability to induce adhesion and respiratory burst of neutrophils. The mouse lungs and kidneys were examined for the development of vasculitis. RESULTS: Mice immunized with human ANCA developed anti-human ANCA and anti-anti-human ANCA (mouse ANCA), while the controls did not develop these antibodies. Mouse ANCA were capable of inducing adhesion of neutrophils to fibronectin and activating the respiratory burst in neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. CONCLUSION: The results suggest a pathogenic role of ANCA in WG, and may imply that activation of neutrophils is the initiating event in the development of vasculitis in WG.

Animals↗
PubMed1995

Myelin- and microbe-specific antibodies in Guillain-Barré syndrome.

We surveyed the frequency of reported infections and target autoantigens in 56 Guillain Barré syndrome (GBS) patients by detecting antibodies to myelin and microbes. Sulfatide (43%), cardiolipin (48%), GD1a (15%), SGPG (11%), and GM3 (11%) antibodies were the most frequently detected heterogenous autoantibodies. A wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps-specific IgG (66%), adenovirus-specific IgG (52%), varicella-zoster virus-specific IgG (46%), and S. pneumoniae serotype 7-specific IgG (45%) were the most prevalent. Our results indicate that polyclonal expansion of physiologic and pathologic antibodies and/or molecular mimicry likely occurs following infection and is related to other autoimmune factors in the etiology of GBS. Although no single definitive myelin-specific autoantibody was identified, our results suggest a unique pattern of reactivity against autoantigens.

Adolescent↗
PubMed1995

Absence of anti-idiotypic antibodies in IVIG preparations to autoantibodies of rare autoimmune diseases.

Intravenous immunoglobulins (IVIG) were found to contain anti-idiotypic antibodies against autoantibodies of various autoimmune diseases. We examined commercial IVIG preparations, from three different manufactures, for the presence of autoantibodies and anti-idiotypic antibodies of two rare autoimmune diseases--primary biliary cirrhosis [anti-pyruvate dehydrogenase (PDH) antibodies] and Goodpasture's syndrome (anti-NC1 antibodies). We used ELISA studies as well as immunoblotting and anti-PDH enzyme activity for the detection of anti-PDH antibodies. ELISA and immunofluorescence studies were used for the detection of anti-NC1 antibodies. The presence of anti-idiotypic activity against anti-PDH fragments on Sepharose-bound IVIG [F(ab)2]. Anti-anti-NC1 activity was evaluated employing inhibition ELISA and immunofluorescence studies. The commercial IVIG preparations that were examined did not contain anti-PDH or anti-NC1 antibodies nor anti-idiotypic activity against these autoantibodies. We conclude that commercial IVIG may lack anti-idiotypic activity against rare autoantibodies.

Anti-Glomerular Basement Membrane Disease↗