Diagnostic methods relating to Graves' disease and other autoimmune disorders

• US 8,178,304 B2
• Filed: 02/20/2007
• Issued: 05/15/2012
• Est. Priority Date: 10/06/2000
• Status: Expired due to Fees

• Current Assignee: Raymond S. Douglas, Terry J. Smith
• Original Assignee: Raymond S. Douglas, Terry J. Smith
• Inventors: Smith, Terry J., Douglas, Raymond S.
• Primary Examiner(s): Rooney, Nora
• Application Number:
  US11/709,334
• Publication Number:
  US 20070218514A1
• Time in Patent Office: 1,911 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9

Abstract

The invention provides methods of diagnosing Graves'"'"' disease (GD), Rheumatoid Arthritis (RA) and other autoimmune diseases in an individual by detecting a disproportionately large fraction of peripheral blood T cells express IGF-1R (CD3⁺ IGF-R⁺) compared to normal control samples. In a further embodiment, the invention provides methods of diagnosing, prognosing, staging, and/or monitoring GD, RA and other autoimmune diseases. Or a predisposition thereto in an individual by detecting a disproportionately large fraction of CD3⁺ IGF-1R⁺ T cells that express CD45RO⁺ compared to normal control samples. In a further embodiment, the invention provides a method of diagnosing, prognosing, staging, and/or monitoring GD, RA and other autoimmune diseases or a predisposition thereto in an individual by detecting an increased CD45RO⁺/RA⁺ ratio in peripheral blood T cells compared to normal control samples. In addition to peripheral blood T cells, the methods of the invention also can be practiced with test samples comprising T cells harvested from affected orbital tissues. Embodiments directed to the prognosis, staging, and/or monitoring of GD, RA and other autoimmune diseases or a predisposition thereto also are provided, along with diagnostic kits for practicing the various embodiments of the invention.

Claims

1. A method of prognosing clinical course in an individual afflicted with Graves'"'"' Disease (GD) comprising (a) obtaining a peripheral blood sample from the individual;

(b) determining the fraction of T cells in the blood sample that express CD3 and IGF-1R (CD3⁺ IGF-1R⁺ T cells); and

(c) relating the determined fraction of CD3⁺ IGF-1R⁺ T cells to the prognosis of disease course, wherein an increased expression compared to a series of controls is used to prognose the clinical course of GD.

2. The method of claim 1 wherein expression of CD3 and IGF-1R is determined by cytometric analysis, Western blot, RT-PCR, radioligand binding, histopathology, or a combination thereof.

3. A method comprising (a) obtaining a peripheral blood sample from an individual;

(b) determining the fraction of CD3⁺ IGF-1R⁺ T cells in the blood sample that express CD45RO⁺; and

(c) relating the determined fraction of CD45RO⁺ T cells to a diagnosis of Graves disease, wherein an increased expression compared to a normal control indicates Graves disease.

4. The method of claim 3 wherein expression of CD45RO is determined by cytometric analysis, Western blot, RT-PCR, radioligand binding, histopathology, or a combination thereof.

5. A method of determining predisposition for Graves'"'"' Disease in an individual comprising (a) obtaining a peripheral blood sample from the individual;

(b) determining the fraction of T cells in the blood sample that express CD3 and IGF-1R (CD3⁺ IGF-1R⁺ T cells); and

(c) relating the determined fraction of CD3⁺ IGF-1R⁺ T cells to the predisposition for Graves'"'"' disease, wherein an increased expression compared to a series of controls determines the predisposition for GD.