Abstract
Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by IgG anti-RBC autoantibodies which can lead to hemolysis. We recently found IgG Fc-glycosylation towards platelet and RBC alloantigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic alloantibodies to FcγRIIIa/b, and hence RBC destruction. It is known that in autoimmune diseases plasma IgG1 galactosylation and sialylation are lowered, but Fc-glycosylation of RBC-specific autoantibodies has never been thoroughly analyzed. We investigated by mass spectrometry the N-linked RBC autoantibody and plasma IgG1 Fc-glycosylation in relation to occurrence of hemolysis for 103 patients with a positive direct antiglobulin test (DAT). We observed that total IgG1 purified from plasma of patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases. The anti-RBC- autoantibodies showed a profile with even lower galactosylation, but higher sialylation and lower bisection levels. In contrast to alloantibodies against RBCs, RBC-bound IgG1 Fc-fucosylation was not different between healthy controls and patients. Analysis of anti-RBC Fc-glycoprofiles suggested that lower bisection and higher galactosylation associate with lower Hb levels.
Highlights
Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by the action of autoantibodies
For the group as a whole, IgG1 fragment crystallizable (Fc)-galactosylation and bisecting GlcNAc were lowered and sialylation was increased for the anti-RBC-IgG1 autoantibodies compared to total IgG1 (Fig. 3A–C)
We found that both lowered anti-RBC bisection for all patients and increased galactosylation in patients with no hemolysis correlated with more severe anemia
Summary
Autoimmune hemolytic anemia (AIHA) is a potentially severe disease in which red blood cells (RBC) are destroyed by the action of autoantibodies. Compared to the glycoforms of total IgG detected in plasma of these women, antigen-specific anti-D, anti-K and anti-Human Platelet Antigen 1a were found to be skewed towards low fucosylation[16, 18, 19], a feature that has only been described for anti-HIV and anti-dengue antibodies[20, 21], but never for any other immune response This lowered core-fucosylation is known to increase the affinity to FcγRIIIa and FcγRIIIb, which correlated with the level of cytopenia in affected neonates[16, 18, 19]. We investigated the glycoprofile of autoantibodies directed against RBC and evaluated whether the glycosylation pattern is related to detection of complement deposition on the RBC membrane and hemoglobin (Hb) level in IgG-mediated AIHA
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