Antibodies to Human Leucocyte Interferons in Cancer Patients

Trown, P. W.; Dennin, R; Krämer, Manfred; Connell, Edward V.; Palleroni, Alicia V.; Quesada, Jorge R.; Gutterman, Jordan U.

doi:10.1016/s0140-6736(83)91737-3

Cited by 95 publications

(21 citation statements)

References 17 publications

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“…Different assays have been used to measure these antibodies: Western blotting ( 5-10), competition in RIAs and ELISAs (11)(12)(13)(14), binding in direct ELISAs (8-10, 15, 16), binding of radiolabeled cytokines (12)(13)(14)(17)(18)(19)(20)(21)(22)(23), and biological interfer-ence assays (7,8,10,15,17,(24)(25)(26)(27). However, other serum factors than antibodies may compete in RIAs and ELISAs, and inhibition of biological activities may be caused by many factors apart from neutralizing antibodies to cytokines (28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Svenson¹,

Hansen²,

Bendtzen³

1993

J. Clin. Invest.

114

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Section: Introductionmentioning

confidence: 99%

Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Svenson¹,

Hansen²,

Bendtzen³

1993

J. Clin. Invest.

114

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“…However, there is no valid explanation for the observed presence of spontaneous anti-IFN-a antibodies in a small number of patients with cancer (8); for the presence of IFN-y antibodies in HIV-infected patients (9), in individuals suffering from various viral diseases, and even (at low titer) in healthy individuals (10); or for the presence of antibodies to all three species of IFN in healthy donors (11,12). The specific increase observed in the anti-IFN-'y antibody titer during viral infection and its decrease following resolution of the disease indicate that these antibodies are related to viral infection, possibly as a consequence of the production of IFN-y after antigenic stimulation in vivo (10).…”

mentioning

confidence: 97%

Natural human antibodies to gamma interferon interfere with the immunomodulating activity of the lymphokine.

Turano

Balsari

Viani

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Natural antibodies to y interferon (IFN-y) were found in patients suffering from different viral diae and, at a lower titer, in healthy individuals. Such antibodies were affinity-purified and studied for their capability to interfere in vitro with the antiviral and immunomodulating activity of IFN-y. Data obtained show that these human anti-IFN-y antibodies have no inhibitory effect on the antiviral activity of IFN-y. On the contrary, they are able to inhibit the expression of Fc receptor sites and HLA-DR antigens induced by IFN-y on the U-937 cells, a human monocytoid/macrophage-derived cell line. These antibodies can also interfere in a mixed lymphocyte culture (MLC) with the proliferation of lymphocytes and the generation of cytotoxic lymphocytes. However, they showed only a moderate inhibitory effect on the cytotoxicity generated in MLC to K-562 cells. Human antibodies capable of interfering with the immunomodulating activities of IFN-y might open up a new field in clinical therapy for those diseases that carry evidence of activated cell-mediated immunity.Interferons (IFNs) form a heterogeneous family of proteins that are defined according to their ability to prevent viral replication (1). So far, three major classes of human IFN have been identified: a, ,3, and y interferons (IFN-a, IFN-P, and IFN-'y). IFN-y shares several characteristics and activities with IFN-a and IFN-,l, but it also mediates various immune functions (2, 3).As self-recognized substances, human IFNs should not elicit antibodies in man, except in conjunction with autoimmune disorders (4) or in patients receiving large amounts of exogenous IFN, administered parenterally over a long period of time (5-7). However, there is no valid explanation for the observed presence of spontaneous anti-IFN-a antibodies in a small number of patients with cancer (8); for the presence of IFN-y antibodies in HIV-infected patients (9), in individuals suffering from various viral diseases, and even (at low titer) in healthy individuals (10); or for the presence of antibodies to all three species of IFN in healthy donors (11,12). The specific increase observed in the anti-IFN-'y antibody titer during viral infection and its decrease following resolution of the disease indicate that these antibodies are related to viral infection, possibly as a consequence of the production of IFN-y after antigenic stimulation in vivo (10).This paper explores the ability of affinity-purified natural human IFN-y antibodies to affect the antiviral and immunomodulating activity of the human lymphokine in vitro. Our results show that affinity-purified human anti-IFN-y antibodies do not impair the antiviral activity of IFN-'y, although they are capable of suppressing the IFN-y induction of class II major histocompatibility complex (MHC) antigens and of Fc receptor sites for immunoglobulin. We also found that natural anti-IFN-y antibodies can interfere, in a mixed lymphocyte culture (MLC), with the proliferation and cytotoxic generation of lymphocytes, probably by inhibitin...

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“…Reports on the presence of autoantibodies to TNF, interleukins, interferons, growth and colony-stimulating factors (CSF) in autoimmune diseases, infections, graft-versus-host, malignancies and apparently healthy individuals followed [17][18][19][20][21][22]. Some studies revealed associations between levels of specific anti-cytokine antibodies and certain clinical manifestations.…”

Section: Discussionmentioning

confidence: 99%