A. Pezzutto

Evaluation of soluble tumor necrosis factor (TNF) receptors and TNF receptor antibodies in patients with systemic lupus erythematodes, progressive systemic sclerosis, and mixed connective tissue disease

Two TNF binding proteins have been characterized as soluble fragments of TNF receptors. We measured the plasma concentrations of soluble type A (p75) and type B (p55) TNF receptors in patients with systemic lupus erythematodes (SLE), progressive systemic sclerosis (PSS), and mixed connective tissue disease (MCTD). In SLE and PSS patients plasma concentrations of both types of TNF receptors and in MCTD patients type A TNF receptors were significantly elevated compared to controls. Plasma concentrations of both soluble TNF receptors were highly correlated in SLE, PSS, and MCTD patients, indicating a possible coregulation of both TNF receptors. In contrast, soluble interleukin 2 receptor (sCD 25) plasma concentrations were not correlated and seem to be an independent parameter. The soluble forms of the TNF receptors neutralize TNF in cytotoxicity assays and are functionally active as TNF antagonists. In one patient with SLE, autoantibodies against type A TNF receptors were detected, TNFα, and TNFβ did not interfere with the autoantibody binding to the receptor.

Elevated TNF receptor plasma concentrations in patients with rheumatoid arthritis.

SummaryTwo types of tumor necrosis factor receptors have been characterized, both capable of transmitting the signal and exerting the biological functions of TNF and lymphotoxin. We measured the plasma concentrations of two types of TNF binding proteins (sTNFR-A and sTNFR-B) in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) using an enzyme-linked binding assay. In normal controls (n = 43), mean plasma concentrations were 1030 ± 55 and 1461 ±59 pg/ml for sTNFR types A and B, respectively. In 67 patients with moderate RA, mean levels were 1422 ± 82 pg/ml (type A) and 2088 ± 109 pg/ml (type B); in 34 patients with severe RA, 2588 ±279 pg/ml and 4494 ± 550 pg/ml, respectively, were measured (P < 0.0001 compared to normal controls). Concentrations of both type A and type B sTNFR were highly correlated in severe RA (R2 = 0.7) but not in SpA or normal controls. T lymphocytes in synovial fluid of patients with RA expressed predominantly type A TNF receptors on their surface; in some patients a weaker expression of type B receptors was also detectable. Soluble TNF binding proteins in patients with RA were able to neutralize TNF in a cytotoxiity assay, demonstrating their ability to act as “TNF-inhibiting factors”. We conclude that both types of TNF receptors are parameters of disease activity in RA and may also act as TNF antagonists.

Treatment modalities and ANCA in Takayasu's arteritis.

As other vasculitic-syndromes Takayasus-Arteritis needs a long-term immunosuppressive therapy in order to control disease-activity. As steroids create many problems in the long run other immunosuppressives should be considered. We report 3 cases treated with low-dose methotrexate. In all patients the arteritis was controlled, steroids reduced or stopped. In the effort to find autoantibodies 16 patients were screened for c-/p-ANCA and neutrophil granular enzymes. In no patient a positive result could be obtained.

Monitoring of a Human B Cell Lymphoma with Monoclonal Antiidiotype Antibodies

Abstract We have raised a set of 5 monoclonal antibodies against idiotype determinants on the tumor cells from a patient with immunocytoma. Though the methods involved are somewhat complex including production of interspecies (human-mouse) and intraspecies (mouse-mouse) hybridomas the technique is feasible. The great advantage of such anti-idiotypic antibodies is that they are practically tumor-specific for the individual patient. The antibodies were employed for the detection of tumor cells in peripheral blood and in lymphoid and hemopoietic organs as well as for quantitative measurement of idiotype-immunoglobulin in the patients serum. Thus, they prove to be valuable tools for monitoring the particular B cell lymphoma.

Monoclonal Antibody (HD 39) Reactive with a Human B Lymphocyte Specific Antigen Expressed on Late Stages of B Cell Maturation

Abstract The monoclonal antibody HD 39 (IgG 1 ) was raised against hairy cell leukemia. HD 39 reacted in studies of cells in suspension only with hairy cell leukemias (strong reaction) and prolymphocytic leukemias. Other types of B cell malignancies and tumors of T cell or myeloid origin were negative. Examination of normal cells showed that the corresponding antigen is exclusively expressed on a subpopulation of B lymphocytes. Cytocentrifuge preparations and immunohistology revealed that the HD 39 antigen occurs also in the cytoplasm: All tumors of the B lineage with HD 39 antigen negative cell surface showed antibody binding to cytoplasmic structures. Results suggest that HD 39 is directed against a B cell differentiation antigen which in cytoplasm seems to be a marker for the entire B cell lineage whereas on cell surface is restricted to the late stages of B cell maturation. This hypothesis is supported by results from phorbol ester (TPA) studies: TPA known to promote cellular differentiation induces the expression of HD 39 on the surface of chronic lymphatic leukemia cells. The monoclonal HD 39 may be useful for the study of normal B cell differentiation and for the classification of B cell neoplasias.