SUMMARY

 

1.  UNC-93B Deficiency is an autosomal recessive defect in innate immunity which results in increased susceptibility to HSV encephalitis. 

 

2.  Two patients with UNC-93B deficiency have been reported.  These patients presented solely with HSV meningo-encephalitis but no other unusual infections.  

 

3.  UNC-93B appears to be important for TLR3, TLR7, TLR8, and TLR9.  Signaling through these receptors leads to inductions of type I interferons (alpha and beta).  Type I interferons trigger the transcription of antiviral proteins, increase viral antigen presentation by MHC class I molecules and activate NK cells.  

 

4.  Conventional tests for humoral and cell-mediated immunity are normal in patients.  Screening of patients can be performed by the measurement of type I interferon induction following stimulation by viruses and TLR7, TLR8, and TLR9 agonists.  Sequencing of the UNC-93B gene can confirm the diagnosis.  

 

5.  HSV infections should be aggressively treated with acyclovir.  The addition of IFN-alpha may be of therapeutic benefit for treatment of severe acute viral infections.  

 

 

 

 

OVERVIEW

 

     UNC-93B Deficiency is an autosomal recessive defect in innate immunity which results in increased susceptibility to HSV encephalitis. 

 

     Two patients with UNC-93B deficiency have been reported.  These patients presented solely with HSV meningo-encephalitis but no other unusual infections.  

         

 

 

 

PATHOGENESIS

 

    UNC-93B appears to be important for TLR3, TLR7, TLR8, and TLR9.  Signaling through these receptors leads to inductions of type I interferons (alpha and beta).  Type I interferons trigger the transcription of antiviral proteins, increase viral antigen presentation by MHC class I molecules and activate NK cells.  

         

 

 

 

EVALUATION

 

The diagnosis of UNC-93B deficiency should be considered in patients with HSV encephalitis.  
    
 Step 1:  Immune Evaluation

 

-Quantitative immunoglobulins (IgG, IgM, IgA) 
-Antibody titers to vaccine antigens   
-Flow cytometry for B cell, T cell, and NK cell enumeration
-Lymphocyte proliferation to mitogens
-NK cell functional assay

 

-The above tests will be normal in patients with UNC-93B deficiency.  However, they should be performed to screen for T cell or NK cell defects that could result in severe HSV infections. 


Step 2:  TLR screening assay

 

-TLR3, 7, 8, and 9 Assay

 

-Measurement of Type I Interferons following stimulation with viruses, TLR7, TLR8, and TLR9 agonists can be a useful screening tool for UNC-93B deficiency.  This test is currently only available at specialized research centers. 

 


Step 3:  Genetic Testing


-UNC-93B gene sequencing

-Testing for G261S (Exon 6) and CTTTdel4 (Exon 8) available through National Jewish

 

 

 

 

 

MANAGEMENT


    HSV infections should be aggressively treated with acyclovir.  The addition of IFN-alpha may be of therapeutic benefit for treatment of severe acute viral infections.  

 

 

 

                                                                         

RESOURCES

Literature Resources

 

1.  Conley 2007 
     UNC-93B Deficiency (summary)
     

2.  Jouanguy 2007 
     Human PID of Type I Interferons (review)