TY  - JOUR
AB  - Desialylation of cell surface glycoproteins carried out by sialidases affects various immunological processes. However, the role of neuraminidase 1 (NEU1), one of four mammalian sialidases, in inflammation and autoimmune disease is not completely unraveled to date. In this study, we analyzed retinal expression of NEU1 in equine recurrent uveitis (ERU), a spontaneous animal model for autoimmune uveitis. Mass spectrometry revealed significantly higher abundance of NEU1 in retinal Müller glial cells (RMG) of ERU-diseased horses compared to healthy controls. Immunohistochemistry uncovered NEU1 expression along the whole Müller cell body in healthy and uveitic state and confirmed higher abundance in inflamed retina. Müller glial cells are the principal macroglial cells of the retina and play a crucial role in uveitis pathogenesis. To determine whether higher expression levels of NEU1 in uveitic RMG correlate with desialylation of retinal cells, we performed lectin binding assays with sialic acid-specific lectins. Through these experiments we could demonstrate a profound loss of both α2-3- and α2-6-linked terminal sialic acids in uveitis. Hence, we hypothesize that higher abundance of NEU1 in uveitic RMG plays an important role in the pathogenesis of uveitis by desialylation of retinal cells. As RMG become activated in the course of uveitis and actively promote inflammation, we propose that NEU1 might represent a novel activation marker for inflammatory RMG. Our data provide novel insights in the expression and implication of NEU1 in inflammation and autoimmune disease.
AU  - Lorenz, L.*
AU  - Amann, B.*
AU  - Hirmer, S.*
AU  - Degroote, R.L.*
AU  - Hauck, S.M.
AU  - Deeg, C.A.*
C1  - 61439
C2  - 50249
CY  - Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
SP  - 873-883
TI  - NEU1 is more abundant in uveitic retina with concomitant desialylation of retinal cells.
JO  - Glycobiology
VL  - 31
IS  - 7
PB  - Oxford Univ Press Inc
PY  - 2021
SN  - 0959-6658
ER  - 

TY  - JOUR
AB  - Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via a hypothesis-free search of loci and genetic variants associated with a trait of interest. Sixteen loci were identified by three previous GWAS of human plasma proteome N-glycosylation. However, the possibility that some of these loci are false positives needs to be eliminated by replication studies, which have been limited so far. Here, we use the largest set of samples so far (4,802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the sixteen loci reported previously, fifteen were replicated in our study. For the remaining locus (near the KREMEN1 gene) the replication power was low, and hence replication results were inconclusive. The very high replication rate highlights the general robustness of the GWAS findings as well as the high standards adopted by the community that studies genetic regulation of protein glycosylation. The fifteen replicated loci present a good target for further functional studies. Among these, eight genes encode glycosyltransferases: MGAT5, B3GAT1, FUT8, FUT6, ST6GAL1, B4GALT1, ST3GAL4, and MGAT3. The remaining seven loci offer starting points for further functional follow-up investigation into molecules and mechanisms that regulate human protein N-glycosylation in vivo.
AU  - Sharapov, S.Z.*
AU  - Shadrina, A.S.*
AU  - Tsepilov, Y.A.*
AU  - Elgaeva, E.E.*
AU  - Tiys, E.S.*
AU  - Feoktistova, S.G.*
AU  - Zaytseva, O.O.*
AU  - Vučković, F.*
AU  - Cuadrat, R.*
AU  - Jäger, S.*
AU  - Wittenbecher, C.*
AU  - Karssen, L.C.*
AU  - Timofeeva, M.*
AU  - Tillin, T.*
AU  - Trbojević-Akmačić, I.*
AU  - Štambuk, T.*
AU  - Rudman, N.*
AU  - Krištić, J.*
AU  - Šimunović, J.*
AU  - Momčilović, A.*
AU  - Vilaj, M.*
AU  - Jurić, J.*
AU  - Slana, A.*
AU  - Gudelj, I.*
AU  - Klarić, T.*
AU  - Puljak, L.*
AU  - Skelin, A.*
AU  - Kadić, A.J.*
AU  - Van Zundert, J.*
AU  - Chaturvedi, N.*
AU  - Campbell, H.*
AU  - Dunlop, M.*
AU  - Farrington, S.M.*
AU  - Doherty, M.*
AU  - Dagostino, C.*
AU  - Gieger, C.
AU  - Allegri, M.*
AU  - Williams, F.*
AU  - Schulze, M.B.*
AU  - Lauc, G.*
AU  - Aulchenko, Y.S.*
C1  - 59336
C2  - 48746
CY  - Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
SP  - 82-88
TI  - Replication of fifteen loci involved in human plasma protein N-glycosylation in 4,802 samples from four cohorts.
JO  - Glycobiology
VL  - 31
IS  - 2
PB  - Oxford Univ Press Inc
PY  - 2021
SN  - 0959-6658
ER  -