Autoimmune myelofibrosis with a TLR8 gain-of-function defect

We report a case of a 25-year-old male with recurrent oral ulcers, upper respiratory tract infections, and an 8-year history of chronic neutropenia. Previously diagnosed with Behçet's disease, the patient had undergone comprehensive hematological evaluations at multiple tertiary institutions, yet the etiology of his persistent neutropenia remained undetermined. Whole-exome sequencing revealed a TLR8-G572D mutation, leading to a diagnosis of autoimmune myelofibrosis (AIMF) secondary to TLR8 gain-of-function (GOF). While concurrent Behçet's disease and neutropenia may occur clinically, the underlying pathogenesis is often neglected. TLR8-GOF screening should be emphasized in young patients with such presentations. To our knowledge, this is the first reported association between TLR8-GOF mutation and AIMF, expanding the phenotypic spectrum of TLR8-related disorders.