Immune modulatory activity of human ribonucleases
First Claim
1. A method of diagnosing an inflammatory syndrome in a patient, comprising:
- determining in a test sample from a patient amount of one or more Rnases; and
comparing the amount to an average amount found in a control sample of a population of healthy humans, wherein an increased amount in the test sample relative to the average amount indicates an inflammatory syndrome in the patient.
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Accused Products
Abstract
Human extracellular ribonucleases (RNases) are widely distributed in various organs and body fluids and together with other members of the mammalian RNase A superfamily. In addition to their RNase activity, several RNases have been shown to have special biological actions, i.e., antitumor, antiviral and angiogenic properties. However, the molecular mechanisms of such activities are unclear. Using protein microarrays amplified rolling circle amplification (RCA), we investigated the effects of EDN (Rnase 2), ECP (Rnase 3) and RNase 1 on leukocytes cytokine production. We measured the levels of 78 different cytokines and growth factors in culture supernatants to determine the cytokine profiles of cells treated with different combinations of RNases and RNase inhibitors. Members of human ribonuclease family (such as Rnase 1, hEDN (Rnase 2) and Rnase 3) induced expression of certain sets of cytokines in human leukocytes, including ENA-78, EOT2, BLC, GDNF, 1309, IFN-α, IFN-γ, IL-10, IL-12P40, IL-12p70, IL-13, IL-16, IL-18, IL-1β, IL-1ra, IL-2Sra, IL-3, IL-6, IL-6sR, IL-7, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCSF, MIG, MDC, MIP-1α, MIP-1β, MPIF-1, NAP-2, RANTES, sCD23, OSM, TARC, TNF-α, TNF-R1 and uPAR. Thus members of the Rnase superfamily are therapeutic targets for treatment of inflammatory diseases and clinical conditions. Inhibition or augmentation of Rnase expression is used to modulate the immune system and is beneficial for host defense against various diseases and is exploited as an adjuvant. The expression of Rnases is a diagnostic marker for inflammation related conditions and is used to determine various disease stages. In addition, expression of cytokines, chemokines, growth factors is used to monitor efficacy of Rnase-base therapies.
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Citations
68 Claims
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1. A method of diagnosing an inflammatory syndrome in a patient, comprising:
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determining in a test sample from a patient amount of one or more Rnases; and
comparing the amount to an average amount found in a control sample of a population of healthy humans, wherein an increased amount in the test sample relative to the average amount indicates an inflammatory syndrome in the patient. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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28. A method of treating a patient with an inflammatory syndrome, comprising:
administering to a patient with an inflammatory syndrome one or more specific inhibitory molecules selected from the group consisting of antibodies and antisense RNA, wherein said specific inhibitory molecules specifically bind to and inhibit a human Rnase. - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44)
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45. A method of preventing an inflammatory syndrome in a patient, comprising:
administering to an organ or tissue transplant patient at risk of developing an inflammatory syndrome, one or more specific inhibitory molecules selected from the group consisting of antibodies and antisense RNA, wherein said specific inhibitory molecules specifically bind to and inhibit a human Rnase.
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46. A method of stimulating an immune response comprising:
administering a human Rnase to a subject in need of an augmented immune response, whereby the subject'"'"'s immune response is increased. - View Dependent Claims (47, 48, 49)
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50. A composition for vaccinating a human comprising:
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an immunogenic antigen; and
a human Rnase.
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51. A method to monitor the effects of Rnase therapy or anti-Rnase therapy, comprising:
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(a) measuring amount of one or more protein selected from the group consisting of ENA-78, EOT2, BLC, GDNF, 1309, IFN-α
, IFN-γ
, IL-10, IL-12P40, IL-12p70, IL-13, IL-16, IL-18, IL-1β
, IL-Ira, IL-2Sra, IL-3, IL-6, IL-6sR, IL-7, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCSF, MIG, MDC, MIP-1α
, MIP-1β
, MPIF-1, NAP-2, RANTES, sCD23, OSM, TARC, TNF-α
, TNF-R1, uPAR, and fragments thereof in a sample collected from a patient at a first time;
(b) repeating step (a) in a sample collected from the patient at a later time;
(c) comparing the amounts measured in step (a) and in step (b), wherein an increased amount over time denotes an effect of an Rnase and a decreased amount denotes an effect of an anti-Rnase therapy.
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52. A method of treating a patient with an inflammatory syndrome, comprising:
administering to a patient with an inflammatory syndrome one or more specific inhibitory molecules which specifically bind to a cellular receptor for a human Rnase, thereby blocking the human Rnase from binding to the cellular receptor. - View Dependent Claims (53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)
Specification