Background We have previously found that activated T-cells from systemic lupus erythematosus (SLE) patients express lower amount of intracellular galectin-1 (icGal-1) than those of healthy controls and are resistant to the apoptotic effect of extracellular galectin-1 (ecGal-1), an endogenous immunoregulatory lectin. We also demonstrated that the de novo synthesized icGal-1 level affects apoptosis of T-cells induced by ecGal-1, since low icGal-1 expression resulted in reduced sentsitivity to ecGal-1 (Deák M et al). We have therefore proposed the defective icGal-1 production to be an explanation to the insufficient regulatory effects of ecGal-1 in SLE. However, altered binding of ecGal-1 to T-cells due to changes in surface glycosylation may also regulate the apoptotic activity of ecGal-1.

Objectives We have herein hypothesized that the cell-surface glycosylation pattern, and consequently, lectin-binding ability in SLE T-cells is altered, and that an abnormal expression of glycosylation enzymes may account for these changes.

Methods In order to analyse the glycosylation pattern of cell surface glycoproteins, lectin-binding assays were performed using 5 different plant lectins and human recombinant Gal-1 on resting and activated T-cells from patients with active SLE (n=8) with multi-colour flow-cytometry, and were compared with 15 healthy controls. mRNA levels of 13 glycosylation enzymes involved in the development of N-glycan structures on T-cells were measured with qPCR, and were correlated with the specific lectin binding data.

Results As compared with the resting state, the increase in Gal-1 binding during activation was significantly lower in SLE T-cells than in controls, and the level of Gal-1 binding maximum was significantly reduced in SLE activated T-cells than in controls. Binding maximum of plant lectins that recognise high complexity N-glycans also increased less in SLE T-cells than in controls during activation. mRNA level of sialyltransferase ST3GAL6 was increased and neuraminidase Neu1 was decreased in active SLE patients as compared to controls. The ST6GAL1/NEU1 ratio in SLE patients positively correlated with the SLEDAI disease activity index.

Conclusions SLE T-cells show decreased complexity of N-glycan structures. Increased ST3GAL6 and decreased Neu1 expression result in an increased density of terminal sialic acids, and this may explain the impaired Gal-1 binding. In addition to the previously described deficiency in icGal-1 expression upon activation, our present findings of an attenuated glycan complexity and a shift toward terminal sialylation provide a further mechanism of pathological T-cell activation and regulation of T-cell viability in SLE.

References

1. Deák M, Hornung Ά, Novák J, Demydenko D, Szabό E, Czibula Ά, Fajka-Boja R, Kriston-Pál Έ, Monostori Έ, Kovács L. Novel role for galectin-1 in T-cells under physiological and pathological conditions. Immunobiology. 2015 Apr;220(4):483–9.

References

Disclosure of Interest None declared