Serum autoantibodies against hexokinase 1 manifest secondary to diabetic macular edema onset

[Display omitted] •- Among patients with DME, 32 % were positive for anti-HK1 autoantibodies.•- Among patients with DME, 12 % were positive for anti-HK2 autoantibodies.•- Anti-HK1 positive were also 7 % of patients with DM and 3 % of control subjects.•- Anti-HK1 autoantibodies fail to predict DME onset.•- Anti-HK1 positivity in vitreous humor corresponded only in part to seropositivity. Autoantibodies against hexokinase 1 (HK1) were recently proposed to be associated with diabetic macular edema (DME). We hypothesized that anti-HK1 autoantibodies can be used as DME markers and to predict DME onset. Serum from patients with 1) DME, 2) diabetes mellitus (DM), 3) allergies or autoimmunities, and 4) control subjects was tested for anti-HK1 and anti-hexokinase 2 (HK2) autoantibodies by immunoblotting. Patients with DM were prospectively followed for up to nine years, and the association of anti-HK1 antibodies with new-onset DME was evaluated. The vitreous humor was also tested for autoantibodies. Among patients with DME, 32 % were positive for anti-HK1 autoantibodies (42 % of those with underlying type 1 DM and 31 % of those with underlying type 2 DM), and 12 % were positive for anti-HK2 autoantibodies, with only partial overlap of these two groups of patients. Anti-HK1 positive were also 7 % of patients with DM, 6 % of patients with allergies and autoimmunities, and 3 % of control subjects. The latter three groups were anti-HK2 negative. Only one of seven patients with DM who were initially anti-HK1 positive developed DME. Anti-HK1 autoantibodies can be used as DME markers but fail to predict DME onset.