Glycosylation (sugar code) is frequently altered on the surface of various cells in patients with immune-mediated diseases resulting in changes in signal transduction and metabolic control. However, alteration of glycosylation patterns of T cells has not yet been characterised in autoimmune disorders. We have previously demonstrated that T-cells of patients with systemic lupus erythematosus (SLE) are resistant to the apoptotic effects of galectin-1 (Gal-1), an immunoregulatory lectin.
T-cells from patients with active SLE (n=18), rheumatoid arthritis (RA) (n=14) or Sjögren’s syndrome (SS) (n=14) and from healthy controls (n=19) were examined. Cell surface glycosylation was analysed with lectin-binding assay, and the expression of glycosyltransferase and glycosidase enzymes participating in the construction of the glycan chains was measured with reverse transcriptase polymerase chain reaction (RT-PCR).
Resting SLE T-cells bound significantly higher amounts of several lectins, while RA and SS resting T-cells were similar to controls in their glycosylation pattern. Activated T-cells from all autoimmune groups bound significantly less Gal-1 than controls, while other lectins bound similarly. Gene expression including alpha mannosidases (MAN1A1, MAN1A2, MAN2A1 and MAN2A2) and beta-N-acetylglucosaminyltransferases (MGAT1–5) in autoimmune activated T-cells did not differ from controls with the only exception of MAN1A2 in SS. However, we found a significant increase in the mRNA ratios of certain sialyltransferases and neuraminidases, specifically in ST6GAL1/NEU1 in SLE and SS, and in ST3GAL6/NEU1 in SLE and RA patients compared to controls. Treatment of cells with neuraminidase resulted in a remarkable increase in Gal-1 binding
The glycosylation pattern of resting SLE T-cells was consistent with a pre-activated phenotype. Decreased Gal-1 binding found in all three diseases can be explained with an increased terminal sialylation, which may be a consequence of an altered expression of sialyltransferase and neuraminidase genes, whose concerted action is responsible for the degree of sialylation of glycan structures. Accordingly, neuraminidase treatment resulted in remarkably increased Gal-1 binding. We propose that increased sialylation may at least partially explain the previously found resistance to the immunoregulatory effects of Gal-1 in SLE, hence contributing to the pathomechanism of the examined diseases.
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