Characterization of a tumor necrosis factor alpha (TNF-alpha) inhibitor: evidence of immunological cross-reactivity with the TNF receptor.

Seckinger, P; Zhang, Jianhua; B, Hauptmann; Dayer, Jean‐Michel

doi:10.1073/pnas.87.13.5188

Cited by 106 publications

(48 citation statements)

References 32 publications

(23 reference statements)

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“…The soluble forms originating from the extramembranous portion of the TNF-RI (sTNF-RI) and TNF-RII (sTNF-RII) can be found in the culture supernatants of lymphocytes, monocytes and neutrophils [15,[19][20][21] and biological fluids [22,23]. The elevation of sTNF-R in serum/plasma and biological fluids reflecting a variety of inflammatory disorders has been shown in several diseases [24][25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Elevation of plasma-soluble tumour necrosis factor receptors (TNF-R) in sarcoidosis

Nakayama

Hashimoto

Amemiya

et al. 1996

Clinical and Experimental Immunology

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SUMMARYTwo types of receptor for tumour necrosis factor-alpha (TNF-R), the 55-kD receptor (TNF-RI) and the 75-kD receptor (TNF-RII), have been identified. Soluble TNF-RI (sTNF-RI) and soluble TNF-RII (sTNF-RII) can be measured in culture supernatants and biological fluids, and the role of sTNF-R has been suggested. In the present study, we measured plasma sTNF-RI and sTNF-RII levels in 19 patients with active sarcoidosis by ELISA in order to assess the state of both types of receptors in this disease. Both plasma sTNF-RI and sTNF-RII levels in patients with active sarcoidosis were significantly higher than those in normal control subjects. A longitudinal evaluation of plasma sTNF-RI and sTNF-RII levels showed that the magnitude of changes in sTNF-RII was closely related with the clinical course of sarcoidosis. These results suggest that plasma sTNF-RII levels may be useful parameters for monitoring the clinical course of sarcoidosis as well as markers for identifying disease activity.

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Section: Introductionmentioning

confidence: 99%

Elevation of plasma-soluble tumour necrosis factor receptors (TNF-R) in sarcoidosis

Nakayama

Hashimoto

Amemiya

et al. 1996

Clinical and Experimental Immunology

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“…TNF-sR released after neutrophil degranulation may compete for TNF-a with TNF cell surface receptors on other neutrophils as well as on surrounding endothelial cells [2,17] and thus act as a TNF-a antagonist [18], protecting the cells against further activation and toxicity of high levels of TNF-a. On the other hand, TNF-sR have been shown in vitro to preserve TNF-a activity by stabilizing its trimeric structure [19] and may thus contribute to the amplification of ANCA-mediated neutrophil activation.…”

Section: Statisticsmentioning

confidence: 99%

Elevated Serum Levels of TNF Soluble Receptors in Patients With Positive Anti-Neutrophil Cytoplasmic Antibodies

Roux‐Lombard

Peter

et al. 1994

Rheumatology

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SUMMARY ANCA are found in various systemic vasculitis and are supposed to play a role in the pathogenesis of the disease, in cooperation with other factors such as cytokines. A total of 36 ANCA-positive and 10 ANCA-negative serum samples were analysed for the presence of TNF soluble receptors (TNF-sR), which are shed from the surface of activated cells and may act as TNF inhibitors. Of the ANCA-positive samples, 67% had elevated TNF-sR75 and 72% had elevated TNF-sR55 compared to ANCA-negative specimens (mean [S.E.] ANTINEUTROPHIL cytoplasmic antibodies, specific for constituents of neutrophil granules and monocyte lysosomes, are present in patients with various systemic vasculitis. Two main types of staining patterns were distinguished on ethanol-fixed neutrophils used as substrate for indirect immunofluorescence microscopy: the cytoplasmic (cANCA) and the perinuclear (pANCA) pattern. Most cANCA are raised against a serine protease, termed proteinase 3 (PR3) or myeloblastine, and are associated with Wegener's granulomatosis, whereas pANCA have specificity for myeloperoxidase or elastase and tend to be associated with idiopathic crescentic glomerulonephritis or necrotizing vasculitis other than Wegener's [1,2]. ANCA levels correlate closely with disease activity, and relapses of Wegener's granulomatosis are preceded by a rise of cANCA levels [3,4]. It thus follows that ANCA may play a role in the pathogenesis of systemic vasculitis. Indeed, it has been shown in vitro that both cANCA and pANCA are able to activate neutrophil respiratory burst and degranulation and to enhance their chemotactic response to fMLP [5,6]. The resulting release of neutrophil proteases and reactive oxygen species may damage endothelial cells, leading to vascular necrosis. This neutrophil activation was most effective after priming neutrophils with TNF-a, known to enhance the expression of adhesion molecules on neutrophils and vascular endothelial cells [5]. TNF binds to two distinct receptors of 55 kDa (TNF-R55) and 75 kDa (TNF-R75) [7], which are expressed in nearly identical amounts at the neutrophil surface [8]. Upon exposure to chemotactic factors, neutrophils shed their surface TNF-R and then release TNF soluble receptors (TNF-sR) which may act as TNF inhibitors [8,9]. We therefore tested sera for a possible MATERIALS AND METHODS Serum specimensA total of 46 serum samples sent to the laboratory for ANCA analysis (19 cANCA-positive, 17 pANCApositive and 10 ANCA-negative) and 21 serum samples obtained from normal blood donors were analysed. ANCA determinationANCA concentrations were determined by flow cytometry using fixed neutrophils as targets [10]. ANCA-positive specimens were further characterized by indirect immunofluorescence to distinguish pANCA staining from cANCA staining [5,11]. TNF-sR measurementTNF-sR55 and TNF-sR75 were assayed by enzymelinked immunological biological assay (ELIBA; F Hoffmann-La Roche, Basel, Switzerland) as previously described [12]. Briefly, 96-well microtitre plates were coated with either monoclonal...

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“…urine [13][14][15][16]. Characterization of these inhibitors revealed two immunologically distinct TNF" binding proteins which were shown to be soluble fragments of the extramcmbrane parts of TNF-R [17][18][19]. The fragments originating from the 55-kD receptor and from the 75-kD receptor arc called TNF-soluble receptor 55 (TNF-sR55) and TNF soluble receptor 75 (TNFsR75) respectively [10,11,20.21 ].…”

Section: Introductionmentioning

confidence: 99%

Tumour necrosis factor soluble receptors behave as acute phase reactants following surgery in patients with rheumatoid arthritis, chronic osteomyelitis and osteoarthritis

Chikanza

Roux‐Lombard

Dayer

et al. 1993

Clinical and Experimental Immunology

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SUMMARY Tumour necrosis factor‐alpha (TNF‐α) is involved in diverse biological processes including immune and inflammatory reactions and the response to surgical stress. Two soluble TNF receptor protein fragments. TNF‐sR55 (from the p55 kD TNF receptor) and TNF‐sR75 (from the p75 kD TNF receptor), are released by cells during inflammation and may modulate the effects of TNF‐α. We have studied the kinetics of secretion of TNF‐α, TNF‐sR55 and TNF‐sR75 in the sera of patients with rheumatoid arthritis (RA) and control subjects with osteoarthritis (OA) or chronic osteomyelitis (OM) before and after major surgery. Significantly higher pre‐operative levels of TNF‐sR55 and TNF‐sR75 were found in RA and OM as compared with OA (P<0.02). Following surgery, TNF‐sR55 increased within 24 h in RA, OM and OA (P<0.05), whereas TNF‐sR75 increased significantly only in OM and OA patients (P<0.05). By contrast, no TNF‐α was detectable before and after surgery in any of the subjects, but this may have been due to impaired detection (by ELISA) of TNF‐α when it is bound to TNF‐sR. These findings suggest that TNF‐sR55 and TNF‐sR75 may be further markers of the host's reaction to inflammatory insults. They may also play a role in modulating the immune and inflammatory reactions by inhibiting the systemic effects of TNF‐α.

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Characterization of a tumor necrosis factor alpha (TNF-alpha) inhibitor: evidence of immunological cross-reactivity with the TNF receptor.

Cited by 106 publications

References 32 publications

Elevation of plasma-soluble tumour necrosis factor receptors (TNF-R) in sarcoidosis

Elevation of plasma-soluble tumour necrosis factor receptors (TNF-R) in sarcoidosis

Elevated Serum Levels of TNF Soluble Receptors in Patients With Positive Anti-Neutrophil Cytoplasmic Antibodies

Tumour necrosis factor soluble receptors behave as acute phase reactants following surgery in patients with rheumatoid arthritis, chronic osteomyelitis and osteoarthritis

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