Diagnostic methods relating to Graves' disease and other autoimmune disorders

• US 20070218514A1
• Filed: 02/20/2007
• Published: 09/20/2007
• Est. Priority Date: 10/06/2000
• Status: Active Grant

• Current Assignee: Trustees of Boston University, Habor UCLA Medical Center Incorporated (University of California)
• Original Assignee: Trustees of Boston University, Habor UCLA Medical Center Incorporated (University of California)
• Inventors: Smith, Terry, Douglas, Raymond
• Granted Patent: US 8,178,304 B2
• Time in Patent Office: Days
• US Class Current: 435/7.240
• 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 diagnosing Graves'"'"' disease (GD) in an individual, said method 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 expression of CD3 and IGF-1R to a diagnosis of Graves disease, wherein an increased expression compared to a normal control indicates a diagnosis of Graves disease.

2. The method of claim I 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 of diagnosing Graves'"'"' disease (GD) in an individual, said method comprising (a) obtaining a peripheral blood sample from the individual;

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

(c) relating the determined expression of CD45RO⁺ to a diagnosis of Graves disease, wherein an increased expression compared to a normal control indicates a diagnosis of 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 diagnosing Graves'"'"' disease (GD) in an individual, said method comprising (a) obtaining a peripheral blood sample from the individual;

(b) determining the ratio of CD45RO⁺/RA⁺ among CD3⁺ IGF-1R⁺ T cells in the blood sample; and

(c) relating the determined ratio to a diagnosis of Graves disease, wherein an increased ration compared to a normal control indicates a diagnosis of Graves disease.

6. The method of claim 5 wherein expression of CD45RO and CD45RA is determined by cytometric analysis, Western blot, RT-PCR, or a combination thereof.

7. A method of diagnosing rheumatoid arthritis (RA) in an individual, said method 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 expression of CD3 and IGF-1R to a diagnosis of rheumatoid arthritis (RA), wherein an increased expression compared to a normal control indicates a diagnosis of rheumatoid arthritis (RA).

8. The method of claim 7 wherein expression of CD3 and IGF-1R is determined by cytometric analysis, Western blot, RT-PCR, radioligand binding, histopathology, or a combination thereof.

9. A method of diagnosing rheumatoid arthritis (RA) in an individual, said method comprising (a) obtaining a peripheral blood sample from the individual;

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

(c) relating the determined expression of CD45RO⁺ to a diagnosis of rheumatoid arthritis (RA), wherein an increased expression compared to a normal control indicates a diagnosis of rheumatoid arthritis (RA).

10. The method of claim 9 wherein expression of CD45RO is determined by cytometric analysis, Western blot, RT-PCR, radioligand binding, histopathology, or a combination thereof.

11. A method of diagnosing rheumatoid arthritis (RA) in an individual, said method comprising (a) obtaining a peripheral blood sample from the individual;

(b) determining the ratio of CD45RO⁺/RA⁺ among CD3⁺ IGF-1R⁺ T cells in the blood sample; and

(c) relating the determined ratio to a diagnosis of rheumatoid arthritis (RA), wherein an increased ration compared to a normal control indicates a diagnosis of rheumatoid arthritis (RA).

12. The method of claim 11 wherein expression of CD45RO and CD45RA is determined by cytometric analysis, Western blot, RT-PCR, or a combination thereof.