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AB0123 T-cell surface glycosylation pattern alterations in sle – a putative link to galectin-1-mediated immunoregulatory deficiency
  1. Ά Hornung1,
  2. E Szabό2,
  3. Ά Czibula2,
  4. Έ Monostori2,
  5. L Kovács1
  1. 1Department of Rheumatology and Immunology, University of Szeged
  2. 2Department of Genetics, Hungarian Academy of Sciences, Biological Research Centre, Szeged, Hungary

Abstract

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

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