TLR3 and UNC93B are proteins necessary to induce type 1 IFN and proinflammatory cytokines, crucial in anti-viral immunity. AD-TLR3 deficiency has been identified as a disorder of HSV-1 encephalitis, not by EBV. Moreover, EBV–encoded small RNA induces signaling from TLR3.
Aim:To report a patient with genetic variations in TLR3 pathway with uncommon symptoms.
Review medical record
An Argentinean 8 years old male, born from non-consanguineous parents. At 7 years old, he has been diagnosed with high-risk B-ALL and CNS involvement. He received systemic and intrathecal protocol V chemotherapy. Immunology profile: hypergammaglobulinemia, normal protein response, complement, and lymphocyte populations. PCR EBV positive in blood. During leukemia treatment, he suffered from common complications.
One year later, he presented a prolonged fever with neurological involvement. EBV was found in blood and CSF, other causes where ruled out. Therefore, secondary encephalitis was assumed, although it was refractory to Rituximab. Moreover, he developed macrophage activation syndrome that remained controlled with immunosuppressive therapy. EBV copies were persistently positive and CNS showed irreversible damage.
In this context, immunology tests showed hypogammaglobulinemia and 0% B-cells after rituximab. Fluctuating hematologic parameters and decreased NKT cells. Since the unexpected outcome, WES was performed: heterozygous variation in TLR3 and NRLP12 and homozygous variation in UNC93B1 genes; all of them with uncertain significance.
This is a first case report with EBV chronic infection and variations in TLR3 pathway. Functional studies are mandatory to confirm the pathogenesis. It is important increase studies when evolution is unusual.