Irf-5 haplotypes in systemic lupus erythematosus

Abstract

Methods and materials involved in diagnosing SLE are provided herein. The methods and materials can be used to diagnose SLE and/or assess a mammal's susceptibility to develop SLE, based on the presence or absence of one or more IRF-5 variants.

1 . A method for assessing the predisposition of a mammal to develop systemic lupus erythematosus (SLE), comprising: 
 (a) determining whether or not said mammal has an IRF-5 haplotype comprising an rs2004640 T allele, an IRF-5 exon 6 insertion allele, and an rs10954213 A allele; and    (b) classifying said mammal as being susceptible to develop SLE if said mammal has said IRF-5 haplotype, or classifying said mammal as not being susceptible to develop SLE if said mammal does not contain said IRF-5 haplotype.    
   
   
       2 . The method of  claim 1 , wherein said mammal is a human.  
   
   
       3 . The method of  claim 1 , further comprising determining whether a biological sample from said mammal contains elevated levels of interferon-α (IFN-α), interleukin-1 receptor antagonist (IL-1 RA), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), or tumor necrosis factor-α (TNF-α).  
   
   
       4 . A method for diagnosing SLE in a mammal, comprising: 
 (a) determining whether or not said mammal has an IRF-5 haplotype comprising an rs2004640 T allele, an IRF-5 exon 6 insertion allele, and an rs10954213 A allele; and    (b) classifying said mammal as being susceptible to develop SLE if said mammal has said IRF-5 haplotype, or classifying said mammal as not being susceptible to develop SLE if said mammal does not have said IRF-5 haplotype.    
   
   
       5 . The method of  claim 4 , wherein said mammal is a human.  
   
   
       6 . The method of  claim 4 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       7 . A method for assessing the predisposition of a mammal to develop SLE, comprising: 
 (a) determining whether or not said mammal has an IRF-5 haplotype comprising an rs2004640 T allele, an IRF-5 exon 6 insertion allele, an rs10954213 A allele, and an rs2070197 C allele; and    (b) classifying said mammal as being susceptible to develop SLE if said mammal has said IRF-5 haplotype, or classifying said mammal as not being susceptible to develop SLE if said mammal does not have said IRF-5 haplotype.    
   
   
       8 . The method of  claim 7 , wherein said mammal is a human.  
   
   
       9 . The method of  claim 7 , further comprising determining whether a biological sample from said mammal contains elevated levels of interferon-α (IFN-α), interleukin-1 receptor antagonist (IL-1 RA), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), or tumor necrosis factor-α (TNF-α).  
   
   
       10 . A method for diagnosing SLE in a mammal, comprising: 
 (a) determining whether or not said mammal has an IRF-5 haplotype comprising an rs2004640 T allele, an IRF-5 exon 6 insertion allele, an rs10954213 A allele, and an rs2070197 C allele; and    (b) classifying said mammal as being susceptible to develop SLE if said mammal has said IRF-5 haplotype, or classifying said mammal as not being susceptible to develop SLE if said mammal does not have said IRF-5 haplotype.    
   
   
       11 . The method of  claim 10 , wherein said mammal is a human.  
   
   
       12 . The method of  claim 10 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       13 . A method for assessing the predisposition of a mammal to develop SLE, comprising: 
 (a) determining whether or not said mammal comprises cells containing a level of an IRF-5 polypeptide that is greater than an average level of an IRF-5 polypeptide in control cells from one or more control mammals, wherein said mammal and said one or more control mammals are from the same species, and wherein said IRF-5 polypeptide in said mammal comprises an amino acid sequence encoded by exon 1B and an amino acid sequence encoded by an insertion in exon 6; and    (b) classifying said mammal as being susceptible to develop SLE if said mammal contains said cells, or classifying said mammal as not being susceptible to develop SLE if said mammal does not contain said cells.    
   
   
       14 . The method of  claim 13 , wherein said mammal is a human.  
   
   
       15 . The method of  claim 13 , wherein said one or more control mammals are healthy humans.  
   
   
       16 . The method of  claim 13 , wherein said cells and said control cells are peripheral blood mononuclear cells or whole blood cells.  
   
   
       17 . The method of  claim 13 , wherein said level of IRF-5 polypeptide in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 10 control mammals.  
   
   
       18 . The method of  claim 13 , wherein said level of IRF-5 polypeptide in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 20 control mammals.  
   
   
       19 . The method of  claim 13 , wherein said determining step comprises measuring the level of IRF-5 mRNA encoding said IRF-5 polypeptide.  
   
   
       20 . The method of  claim 13 , wherein said determining step comprises measuring the level of said IRF-5 polypeptide.  
   
   
       21 . The method of  claim 13 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       22 . A method for diagnosing SLE in a mammal, comprising: 
 (a) determining whether or not said mammal comprises cells containing a level of an IRF-5 polypeptide that is greater than an average level of an IRF-5 polypeptide in control cells from one or more control mammals, wherein said mammal and said one or more control mammals are from the same species, and wherein said IRF-5 polypeptide in said mammal comprises an amino acid sequence encoded by exon 1B and an amino acid sequence encoded by an insertion in exon 6; and    (b) classifying said mammal as being susceptible to develop SLE if said mammal contains said cells, or classifying said mammal as not being susceptible to develop SLE if said mammal does not contain said cells.    
   
   
       23 . The method of  claim 22 , wherein said mammal is a human.  
   
   
       24 . The method of  claim 22 , wherein said one or more control mammals are healthy humans.  
   
   
       25 . The method of  claim 22 , wherein said cells and said control cells are peripheral blood mononuclear cells or whole blood cells.  
   
   
       26 . The method of  claim 22 , wherein said level of IRF-5 in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 10 control mammals.  
   
   
       27 . The method of  claim 22 , wherein said level of IRF-5 polypeptide in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 20 control mammals.  
   
   
       28 . The method of  claim 22 , wherein said determining step comprises measuring the level of IRF-5 mRNA encoding said IRF-5 polypeptide.  
   
   
       29 . The method of  claim 22 , wherein said determining step comprises measuring the level of IRF-5 polypeptide.  
   
   
       30 . The method of  claim 22 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       31 . A method for determining the likelihood of a mammal to respond to treatment with a therapy directed to IRF-5, comprising: 
 (a) determining whether or not said mammal has an IRF-5 haplotype comprising an rs2004640 T allele, an IRF-5 exon 6 insertion allele, and an rs10954213 A allele; and    (b) classifying said mammal as likely to respond to said therapy if said mammal has said IRF-5 haplotype, or classifying said mammal as not being likely to respond to said therapy if said mammal does not have said IRF-5 haplotype.    
   
   
       32 . The method of  claim 31 , wherein said mammal is a human.  
   
   
       33 . The method of  claim 31 , wherein said mammal is diagnosed as having SLE.  
   
   
       34 . The method of  claim 31 , wherein a response to said therapy comprises a reduction in one or more symptoms of SLE.  
   
   
       35 . The method of  claim 31 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       36 . A method for determining the likelihood of a mammal to respond to treatment with a therapy directed to IRF-5, comprising: 
 (a) determining whether or not said mammal comprises cells containing a level of an IRF-5 polypeptide that is greater than an average level of an IRF-5 polypeptide in control cells from one or more control mammals, wherein said mammal and said one or more control mammals are from the same species, and wherein said IRF-5 polypeptide in said mammal comprises an amino acid sequence encoded by exon 1B and an amino acid sequence encoded by an insertion in exon 6; and    (b) classifying said mammal as likely to respond to said therapy if said mammal contains said cells, or classifying said mammal as not being likely to respond to said therapy if said mammal does not contain said cells.    
   
   
       37 . The method of  claim 36 , wherein said mammal is a human.  
   
   
       38 . The method of  claim 36 , wherein said mammal is diagnosed as having SLE.  
   
   
       39 . The method of  claim 36 , wherein said one or more control mammals are healthy humans.  
   
   
       40 . The method of  claim 36 , wherein said cells and said control cells are peripheral blood mononuclear cells or whole blood cells.  
   
   
       41 . The method of  claim 36 , wherein said level of IRF-5 polypeptide in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 10 control mammals.  
   
   
       42 . The method of  claim 36 , wherein said level of IRF-5 polypeptide in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 20 control mammals.  
   
   
       43 . The method of  claim 36 , wherein said determining step comprises measuring the level of IRF-5 mRNA encoding said IRF-5 polypeptide.  
   
   
       44 . The method of  claim 36 , wherein said determining step comprises measuring the level of IRF-5 polypeptide.  
   
   
       45 . The method of  claim 36 , wherein a response to said therapy comprises a reduction in one or more symptoms of SLE.  
   
   
       46 . The method of  claim 36 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       47 . The method of  claim 36 , comprising determining whether or not said mammal contains detectable levels of an IRF-5 mRNA having a truncated 3′ untranslated region.  
   
   
       48 . A method for determining the likelihood of a mammal to respond to treatment with a therapy directed to a cytokine or a Toll like receptor (TLR), comprising: 
 (a) determining whether or not said mammal has an IRF-5 haplotype comprising an rs2004640 T allele, an IRF-5 exon 6 insertion allele, and an rs10954213 A allele; and    (b) classifying said mammal as likely to respond to said treatment if said mammal has said IRF-5 haplotype, or classifying said mammal as not being likely to respond to said treatment if said mammal does not have said IRF-5 haplotype.    
   
   
       49 . The method of  claim 48 , wherein said cytokine is IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       50 . The method of  claim 48 , wherein said TLR is TLR7, TLR8, or TLR9.  
   
   
       51 . The method of  claim 48 , wherein said mammal is a human.  
   
   
       52 . The method of  claim 48 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       53 . A method for determining the likelihood of a mammal to respond to treatment with a therapy directed to a cytokine or a TLR, comprising: 
 (a) determining whether or not said mammal comprises cells containing a level of an IRF-5 polypeptide that is greater than an average level of an IRF-5 polypeptide in control cells from one or more control mammals, wherein said mammal and said one or more control mammals are from the same species, and wherein said IRF-5 polypeptide in said mammal comprises an amino acid sequence encoded by exon 1B and an amino acid sequence encoded by an insertion in exon 6; and    (b) classifying said mammal as likely to respond to said treatment if said mammal contains said cells, or classifying said mammal as not being likely to respond to said treatment if said mammal does not contain said cells.    
   
   
       54 . The method of  claim 53 , wherein said cytokine is IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.  
   
   
       55 . The method of  claim 53 , wherein said TLR is TLR7, TLR8, or TLR9.  
   
   
       56 . The method of  claim 53 , wherein said mammal is a human.  
   
   
       57 . The method of  claim 53 , wherein said one or more control mammals are healthy humans.  
   
   
       58 . The method of  claim 53 , wherein said cells and said control cells are peripheral blood mononuclear cells or whole blood cells.  
   
   
       59 . The method of  claim 53 , wherein said level of IRF-5 polypeptide in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 10 control mammals.  
   
   
       60 . The method of  claim 53 , wherein said level of IRF-5 polypeptide in said mammal is greater than the average level of IRF-5 polypeptide in control cells from at least 20 control mammals.  
   
   
       61 . The method of  claim 53 , wherein said determining step comprises measuring the level of IRF-5 mRNA encoding said IRF-5 polypeptide.  
   
   
       62 . The method of  claim 53 , wherein said determining step comprises measuring the level of IRF-5 polypeptide.  
   
   
       63 . The method of  claim 53 , further comprising determining whether a biological sample from said mammal contains elevated levels of IFN-α, IL-1RA, IL-6, MCP-1, MIP-1α, MIP-1β, or TNF-α.