Recombination sequence (RS) rearrangement frequency as a measure of central B cell tolerance

Patent metadata

Field	Value
Publication number	US-9115399-B2
Application number	US-200913120324-A
Country	US
Kind code	B2
Filing date	Sep 23, 2009
Priority date	Sep 23, 2008
Publication date	Aug 25, 2015
Grant date	Aug 25, 2015

Abstract

The invention relates to methods and materials for diagnosing an autoimmune disease such as SLE, Type 1 diabetes, and the like. More particularly, the invention relates to methods and materials for assessing the frequency of recombination sequence (RS) rearrangement as a novel marker for an autoimmune disease. Such an assay can allow clinicians to diagnose an autoimmune disease based on the RS rearrangement frequency in an autoimmune patient as compared to an otherwise healthy control. In addition, the method includes identifying individuals who are at increased risk of developing autoimmunity. The method may also be helpful in directing the type of therapy and monitoring the effects of therapy in patients with autoimmune or non-autoimmune conditions.

First claim

What is claimed is:

1. A method of diagnosing an autoimmune disease in a mammal, the method comprising obtaining DNA from a blood sample obtained from the mammal; measuring the frequency of recombination sequence (RS) rearrangement in the DNA obtained from the mammal; and calibrating the measured frequency of RS rearrangement by at least one of B cell fraction and κ/λ ratio in the blood sample, wherein a reduced level of RS rearrangement compared to the level of RS rearrangement in an otherwise identical healthy mammal is an indication that said mammal has an autoimmune disease.

2. The method of claim 1 , wherein the reduced level of RS rearrangement confers an increased risk of the future development of autoimmunity.

3. The method of claim 1 , wherein said autoimmune disease is type 1 diabetes.

4. The method of claim 1 , wherein said autoimmune disease is systemic lupus erythematosus (SLE).

5. The method of claim 1 , wherein said mammal is a human.

6. The method of claim 1 , wherein said RS rearrangement is measured based on quantitative PCR.

7. A method of diagnosing an autoimmune disease in a mammal, the method comprising obtaining DNA from a blood sample obtained from the mammal; measuring the frequency of recombination sequence (RS) rearrangement in the DNA obtained from the mammal; and calibrating the measured frequency of RS rearrangement by at least one of B cell fraction and κ/λ ratio in the blood sample, without the use of flow cytometry, wherein a reduced level of RS rearrangement compared to the level of RS rearrangement in an otherwise identical healthy mammal is an indication that said mammal has an autoimmune disease.

Assignees

• Panigrahi Anil K
• Prak Eline Luning
• Univ Pennsylvania

Inventors

• Panigrahi Anil K
• Prak Eline Luning

Classifications

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title