US 2012/0237954 A1Published application

Biomarkers for prognoses of pulmonary diseases

AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education

InventorSteven R. Duncan

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Abstract

The present invention relates to biomarkers that may be used to evaluate the prognoses of patients suffering from pulmonary diseases and assist in the determination of appropriate therapeutic regimens. It is based, at least in part, on the discovery that a number of T-cell antigens are differentially expressed in chronic lung disease patients depending on the prognosis of the patient. Non-limiting examples of these antigens include CD28, CD4, CD25, CD45, CD27 and CCR7 and combinations thereof. Use of these biomarker antigens, optionally in conjunction with pulmonary function tests, provides an indication of which patients are likely to suffer a severely adverse outcome within the year and/or be refractory to treatment.

Claims12

Dependent claims

A method of determining the risk that a subject suffering from a chronic pulmonary disease will suffer a severe adverse event, comprising determining whether, in a sample comprising T-cells collected from the subject, one or more of the following is present:

the proportion of CD4+CD28null cells among the Cd4+ T-cell population is elevated, where said elevation indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD4+ cells among the peripheral blood mononuclear cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD25+ cells among the CD4+ T-cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD28+ cells among the CD8+ T-cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD4+CD45+RO CD45RO+ cells among the CD4+ T-cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of HLA-DR+ cells among the CD4+ T-cell population is increased, where said increase indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD27+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates that the subject is at increased risk of suffering an adverse event;
the proportion of CCR7+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates that the subject is at increased risk of suffering an adverse event;
the proportion of IL-7R+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of CD3+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of CD80+ cells among the CD4+ T-cell population is increased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of CTLA-4+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of ICOS+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of Itk+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of Ltk+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of granzyme B produced by CD4+ T-cells of the subject is increased relative to T-cells of a healthy control, where said increase indicates that the subject is at increased risk of suffering an adverse event;
the proportion of FoxP3 produced by CD4+ T cells of the subject is decreased relative to T cells of a healthy control, where said decrease indicates that the subject is at increased risk of suffering an adverse event;
and
the proportion of perforin produced by CD4+ T-cells of the subject is increased relative to T-cells of a healthy control, where said increase indicates that the subject is at increased risk of suffering an adverse event.

16 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/432,227Filed 28 Mar 2012
Priority: 8 Oct 2010
Published: 20 Sep 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

G01N 21/6486
Fluorescence; Phosphorescence: measuring fluorescence of biological material, e.g. DNA, RNA, cells
C07K 16/2866
Against receptors, cell surface antigens or cell surface determinants: against receptors for cytokines, lymphokines, interferons
C07K 16/2893
Against receptors, cell surface antigens or cell surface determinants: against CD52
G01N 33/505
Cells of the immune system: involving T-cells

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Application13/432,227Continuation
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Abstract

the proportion of CD4+CD28null cells among the Cd4+ T-cell population is elevated, where said elevation indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD4+ cells among the peripheral blood mononuclear cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD25+ cells among the CD4+ T-cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD28+ cells among the CD8+ T-cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD4+CD45+RO CD45RO+ cells among the CD4+ T-cell population is decreased, where said decrease indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of HLA-DR+ cells among the CD4+ T-cell population is increased, where said increase indicates that the subject is at increased risk of suffering a severe adverse event;
the proportion of CD27+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates that the subject is at increased risk of suffering an adverse event;
the proportion of CCR7+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates that the subject is at increased risk of suffering an adverse event;
the proportion of IL-7R+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of CD3+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of CD80+ cells among the CD4+ T-cell population is increased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of CTLA-4+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of ICOS+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of Itk+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of Ltk+ cells among the CD4+ T-cell population is decreased relative to a healthy control, where said decrease indicates the subject is at increased risk of suffering an adverse event;
the proportion of granzyme B produced by CD4+ T-cells of the subject is increased relative to T-cells of a healthy control, where said increase indicates that the subject is at increased risk of suffering an adverse event;
the proportion of FoxP3 produced by CD4+ T cells of the subject is decreased relative to T cells of a healthy control, where said decrease indicates that the subject is at increased risk of suffering an adverse event;
and
the proportion of perforin produced by CD4+ T-cells of the subject is increased relative to T-cells of a healthy control, where said increase indicates that the subject is at increased risk of suffering an adverse event.

16 more elements

Facts

Application

13/432,227Filed 28 Mar 2012

Priority

8 Oct 2010

Published

20 Sep 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

G01N 21/6486
Fluorescence; Phosphorescence: measuring fluorescence of biological material, e.g. DNA, RNA, cells
C07K 16/2866
Against receptors, cell surface antigens or cell surface determinants: against receptors for cytokines, lymphokines, interferons
C07K 16/2893
Against receptors, cell surface antigens or cell surface determinants: against CD52
G01N 33/505
Cells of the immune system: involving T-cells