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)