Diagnostic test using fc receptor

Abstract

The present invention provides a method for determining whether a patient has a predisposition to infection by certain encapsulated bacteria. The method involves determining whether the Fcγ receptor allelic pattern of the patient corresponds most closely to known Fcγ receptor allelic patterns of patients having no infection.

What we claim is:  
     
         1 . A diagnostic method for determining predisposition to severe forms of autoimmune disease in a patient, comprising 
 (i) identifying the Fcγ receptor allelic pattern of said patient;    (ii) comparing said allelic pattern with the corresponding allelic patterns of humans with no autoimmune disease, mild autoimmune disease, and severe autoimmune disease; and    (iii) determining which of said corresponding allelic patterns is most similar to the allelic pattern of said patient.    
     
     
         2 . The method of    claim 1   , wherein said autoimmune disease is a member selected from the group consisting of systemic lupus erythematosus, systemic vasculitides, Sjogren's sydrome, mixed connective tissue disease, rheumatoid arthritis, and glomerulonephritis.  
     
     
         3 . The method of    claim 2   , wherein said systemic vasculitis comprises Wegener's granulomatosis.  
     
     
         4 . The method of    claim 1   , wherein said severe autoimmune disease is characterized by symptoms selected from the group consisting of nephritis, vasculitis, and lung disease.  
     
     
         5 . The method of    claim 1   , which comprises identifying the alleles of FcγRIIIB of said patient.  
     
     
         6 . The method of    claim 5   , wherein said FcγRIIIB alleles comprise the NA1 and NA2 alleles.  
     
     
         7 . The method of    claim 1   , wherein said identifying step comprises: 
 (a) obtaining white blood cells from said human;    (b) contacting said cells with antibodies specific for different allelic forms of the Fcγ receptor protein; and    (c) determining which of said antibodies binds specifically to said cells.    
     
     
         8 . The method of    claim 6   , wherein said determining step comprises quantitative flow cytometry.  
     
     
         9 . The method of    claim 6   , wherein said determining step comprises enzyme-linked immunoassay.  
     
     
         10 . The method of    claim 1   , wherein said identifying step comprises: 
 (a) obtaining DNA from said human; and    (b) determining the sequence of polymorphic regions of genes encoding Fcγ receptors contained within said DNA.    
     
     
         11 . The method of    claim 1   , wherein said identifying step comprises: 
 (a) obtaining DNA from said human;    (b) amplifying regions of said DNA containing said Fcγ receptor genes or fragments thereof;    (c) hybridizing said amplified DNA with one or more allele-specific oligonucleotides; and    (d) identifying the oligonucleotides that hybridize specifically with said DNA.    
     
     
         12 . The method of    claim 1   , wherein said identifying step comprises: 
 (a) obtaining white blood cells from said human;    (b) isolating RNA from said cells;    (c) subjecting said RNA to coupled reverse transcription and amplification specified by Fcγ receptor allele-specific oligonucleotide primers, to produce Fcγ receptor-encoding DNA; and    (d) determining the sequence of said DNA.    
     
     
         13 . A diagnostic method for determining predisposition to severe forms of Wegener's granulomatosis in patients suffering from Wegener's granulomatosis, comprising 
 (i) obtaining DNA samples from said patients;    (ii) amplifying the regions of said DNA samples containing FcγRIIIB genes;    (iii) individually hybridizing parallel samples of said amplified DNAs with oligonucleotides specific for the NA1 and NA2 alleles of said FcγRIIIB genes; and    (iv) identifying the DNA samples that are homozygous for said FcγRIIIB NA1 allele.    
     
     
         14 . The method of    claim 12   , further comprising monitoring the titer of anti-neutrophil cytoplasmic antibodies in said patients.  
     
     
         15 . The method of    claim 12   , further comprising identifying the alleles of FcγRIIA of said patient.