Methods and compositions useful in the diagnosis and treatment of autoimmune diseases

• US 4,751,181 A
• Filed: 12/31/1984
• Issued: 06/14/1988
• Est. Priority Date: 12/31/1984
• Status: Expired due to Term

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Keene, Jack D.
• Primary Examiner(s): Tanenholtz, Alvin E.
• Application Number:
  US06/687,908
• Time in Patent Office: 1,261 Days
• Field of Search: 435/70, 435/172.3, 435/317, 435/6, 435/7, 436/506, 436/507, 436/508
• US Class Current: 435/69.3
• CPC Class Codes: A61K 39/0008 Antigens related to auto-immune diseases; Preparations to induce self-tolerance
• CPC Class Codes: C07K 14/4713 Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
• CPC Class Codes: C12N 15/11 DNA or RNA fragments; Modified forms thereof DNA or RNA not used in recombinant technology, C07H21/00; Non-coding nucleic acids having a biological activity
• CPC Class Codes: G01N 2800/24 Immunology or allergic disorders SLE G01N2800/104
• 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
• CPC Class Codes: Y10S 436/811 Test for named disease, body condition or organ function

Abstract

A method for producing a protein antigen which is reactive with an autoantibody associated with an autoimmune disease in a host, which comprises introducing genetic information from a cross-reactive donor gene library, into plural cells thereby producing transformed cells; selecting a producer cell which expresses said antigen by detecting a binding reaction between said autoantibody obtained from said host and a protein antigen expressed by a producer cell of said transformed cells which contains a gene coding for said protein antigen, thereby identifying a cloned DNA segment from said donor which can be utilized in the production of said protein, is disclosed along with biochemical reagents and products associated with this invention.

Claims

1. A method for producing a La protein antigen which is reactive with an autoantibody associated with systemic lupus erythematosus in a host, which comprises:

introducing genetic information from a gene library obtained from a first host into plural recipient cells, wherein said gene library is obtained from a host that expresses a La protein antigen reactive with said autoanitbody, thereby producing transformed cells;

selecting a producer cell from said transformed cells which contains a gene coding for said La protein antigen and which expresses said antigen by detecting a binding reaction between an autoantibody obtained from a second and different host and protein antigen expressed by said producer cell, thereby identifying a cloned DNA segment which can be utilized in the production of said protein antigen.

4. The method of claim 1, wherein said first host is a human.

5. The method of claim 1, wherein said second and different host is a human.

8. The method of claim 1, wherein said donor gene library is a cDNA gene library.

2. A method for producing a La protein antigen which is reactive with an autoantibody associated with systemic lupus erythematosus in a host, which comprises:

introducing genetic information from a gene library obtained from a first host into plural recipient cells, wheein said gene library is obtained from a host that expresses a La protein antigen reactive with said autoantibody, thereby producing transformed cells;

selecting a producer cell from said transformed cells which contains a gene coding for said La protein antigen and which expresses said antigen by detecting a binding reaction between an autoantibody obtained from a second and different host and protein antigen expressed by said producer cell, thereby identifying a cloned DNA segment which can be utilized in the production of said protein;

cloning said producer cells; and

obtaining said La protein antigen expressed by said producer cell.

6. The method of claim 2, wherein said first host is a human.

7. The method of claim 2, wherein said second and different host is a human.

9. The method of claim 2, wherein said donor gene library is a cDNA gene library.

3. A method for producing a La protein antigen which is a reactive with an autoantibody associated with systemic lupus erythematosus in a host, which comprises:

introducing genetic information from a gene library obtained from a first host into plural recipient cells, wherein said gene library is obtained from a host that expresses a La protein antigen reactive with said autoantibody, thereby producing transformed cells;

selecting a producer cell from said transformed cells which contains a gene coding for said La protein antigen and which expresses said antigen by detecting a binding reaction between an autoantibody obtained from a second and different host and the protein antigen expressed by said producer cell, thereby identifying a cloned DNA segment which can be utilized in the poroduction of said protein;

sequencing said gene or said La protein antigen; and

synthesizing said La protein by chemical means.

10. A recombinant DNA expression vector, wherein said vector comprises an expressible DNA segment which codes for a La protein antigen which is reactive with an autoantibody associated with systemic lupus erythemtosus.

11. The vector of claim 10, wherein said segment codes for at least 66 amino acids at the carboxy terminal of a human La protein antigen.