Genetic polymorphism in the receptor for IgA

• US 6,986,987 B1
• Filed: 07/23/1999
• Issued: 01/17/2006
• Est. Priority Date: 07/24/1998
• Status: Expired due to Fees

• Current Assignee: UAB Research Foundation (University of Alabama System)
• Original Assignee: UAB Research Foundation (University of Alabama System)
• Inventors: Kimberly, Robert P.
• Primary Examiner(s): Fredman, Jeffrey
• Assistant Examiner(s): MERKLING, SALLY ANNE
• Application Number:
  US09/744,373
• Time in Patent Office: 2,370 Days
• Field of Search: 435/91.1, 435/91.2, 435/6, 536/23.1, 536/24.1
• US Class Current: 435/6.14
• CPC Class Codes: G01N 2800/104 Lupus erythematosus [SLE]
• CPC Class Codes: G01N 2800/18 Dental and oral disorders
• 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: G01N 33/6854 Immunoglobulins

Abstract

A method and a package for identifying single nucleotide polymorphisms in FcαRI is useful in identifying individual susceptibility to a disease. FcαRI is active as a cellular receptor of IgA. The susceptibility and severity of an IgA related disease is determined by genotyping or phenotyping an individual for FcαRI.

Claims

1. A method of correlating an Fcα

RI induced function of intracellular calcium flux or interleukin-6 release or TNFα

release of a cell in a host expressing Fcα

RI with an Fcα

RI amino acid sequence, said method comprising;

identifying said Fcα

RI genotype of said cell at nucleotide 844 corresponding to an amino acid sequence codon 248 as being glycine;

quantifying said Fcα

RI induced function by said cell expressing Fcα

RI; and

comparing Fcα

RI induced function by said cell and Fcα

RI induced function by a second cell, said second cell expressing a second Fcα

RI genotype at nucleotide 844 that corresponds to serine at said amino acid sequence codon 248, wherein the Fcα

RI induced function of intracellular calcium flux or interleukin-6 release or TNFα

release of the cell in the host expressing Fcα

RI correlates with the Fcα

RI amino acid sequence codon 248.

2. The method of claim 1 wherein said cell is selected from the group consisting of:

a neutrophil, a monocyte, a myeloid cell, and a mucus secreting cell.

3. A method for determining Fcα

RI induced function of increased intracellular calcium flux or greater interleukin-6 release or less TNFα

release specific to an individual human, said method comprising;

genotyping DNA encoding Fcα

RI for nucleotide 844 corresponding to a codon identity at codon 248 as being glycine, said DNA being obtained from said individual human, wherein the Fcα

RI induced function specific to said individual human is relative to codon 248 being serine.

4. The method of claim 3 wherein genotyping utilizes PCR typing with a sequence specific primer for a polymorphic exon.

5. The method of claim 4 wherein said primer is selected from the group consisting of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, or SEQ ID No. 4.

6. A method of prognosticating a human CD89 expressing cellular response, said method comprising:

establishing a correlation between a Fcα

RI genotype at nucleotide 844 as to A and a cellular response selected from the group consisting of;

increased intracellular calcium flux, greater interleukin-6 release and less TNFα

release relative to nucleotide 844 being G;

genotyping a patient for Fcα

RI to yield a patient Fcα

RI genotype at nucleotide 844;

comparing said Fcα

RI genotype with said patient genotype; and

determining said cellular response based on said patient genotype, wherein the human CD89 expressing cellular response is prognosticated based on the nucleotide 844 genotype being A and the cellular response is selected from the group consisting of;

increased intracellular calcium flux, greater interleukin-6 release and less TNFα

release.

7. The method of claim 6 wherein genotyping utilizes PCR typing with a sequence specific primer for a polymorphic exon.

8. The method of claim 7 wherein said primer is selected from the group consisting of those shown in SEQ ID Nos. 1, 2, 3 and 4.

9. The method of claim 6 wherein genotyping comprises purifying Fcα

RI expressing cells from said patient;

extracting nucleic acids from said cells; and

determining whether the nucleic acid encodes a predetermined polymorphic Fcα

RI nucleic acid sequence.

10. The method of claim 9 wherein the nucleic acid is selected from the group consisting of:

RNA and DNA.