Aims/hypothesis Anti-zinc transporter (ZnT)8 autoantibodies are commonly detected in type 1 diabetic patients. We hypothesized that ZnT8 is also recognized by CD8+ T cells and aimed at identifying HLA-A2 (A*02:01)-restricted epitope targets. Methods Candidate epitopes were selected by ZnT8 plasmid DNA immunization of HLA-A2/DQ8-transgenic mice and tested for T-cell recognition in peripheral blood mononuclear cells of type 1 diabetic, type 2 diabetic and healthy subjects by IFN-γ enzyme-linked immunospot. Results Caucasian HLA-A2+ type 1 diabetic patients, both adults (83%) and children (60%),displayed ZnT8-reactive CD8+ T cells which recognized a single ZnT8186–194 (VAANIVLTV) epitope. This ZnT8186–194-reactive fraction accounted for 50–53% of total ZnT8-specific CD8+ T cells. Another ZnT8153–161 (VVTGVLVYL) sequence was recognized in 20–25% of type 1 diabetic adults and children, respectively. Both epitopes were type 1 diabetes-specific, being marginally recognized by type 2 diabetic and healthy subjects (7–12% for ZnT8186–194 and 0% for ZnT8153–161). Conclusions/interpretation ZnT8-reactive CD8+ T cells are predominantly directed against the ZnT8186–194 epitope and are detected in a majority of type 1 diabetic patients. The exceptional immunodominance of ZnT8186–194 may point to common environmental triggers precipitating beta-cell autoimmunity.

Hemophagocytic lymphohistiocytosis (HLH) is a rare heterogeneous group of disorders characterized by immune overactivation. It can occur because of primary genetic mutations or secondary to almost any inflammatory or infectious process. The clinical manifestations of this syndrome are varied and life-threatening and resemble those of many malignancies, infections, sepsis, and multisystem inflammatory syndrome in children. Laboratory abnormalities often are not diagnostic for HLH until late in the disease course, and the laboratory studies are send-out tests at most institutions. Thus, quickly and accurately diagnosing pediatric patients with HLH presents significant challenges to the clinician. Furthermore, there has been recent discussion in the literature regarding the use of diagnostic criteria for HLH. In this case report, we detail an adolescent male individual who developed persistent unexplained fever, rhabdomyolysis, and regional ischemic immune myopathy. To our knowledge, there is no previous report of a pediatric patient with this rare myopathy or HLH presenting with persistent rhabdomyolysis in the literature. The patient was hospitalized for a total of 61 days, with multiple treatments attempted throughout during his course of illness. In this report, we highlight the importance of using diagnostic flexibility when HLH is suspected in pediatric patients and provide insight into the unique challenges of identifying this condition.