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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arthritis+Rheumatol
2015 ; 67
(11
): 2978-89
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Association of systemic lupus erythematosus with decreased immunosuppressive
potential of the IgG glycome
#MMPMID26200652
Vu?kovi? F
; Kri?ti? J
; Gudelj I
; Teruel M
; Keser T
; Pezer M
; Pu?i?-Bakovi? M
; ?tambuk J
; Trbojevi?-Akma?i? I
; Barrios C
; Pavi? T
; Menni C
; Wang Y
; Zhou Y
; Cui L
; Song H
; Zeng Q
; Guo X
; Pons-Estel BA
; McKeigue P
; Leslie Patrick A
; Gornik O
; Spector TD
; Harja?ek M
; Alarcon-Riquelme M
; Molokhia M
; Wang W
; Lauc G
Arthritis Rheumatol
2015[Nov]; 67
(11
): 2978-89
PMID26200652
show ga
OBJECTIVE: Glycans attached to the Fc portion of IgG are important modulators of
IgG effector functions. Interindividual differences in IgG glycome composition
are large and they associate strongly with different inflammatory and autoimmune
diseases. IKZF1, HLA-DQ2A/B, and BACH2 genetic loci that affect IgG glycome
composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a
potentially causative role of aberrant IgG glycosylation in SLE. We undertook
this large multicenter case-control study to determine whether SLE is associated
with altered IgG glycosylation. METHODS: Using ultra-performance liquid
chromatography analysis of released glycans, we analyzed the composition of the
IgG glycome in 261 SLE patients and 247 matched controls of Latin American
Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of
different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE
patients and 105 controls from China). RESULTS: Multiple statistically
significant differences in IgG glycome composition were observed between patients
and controls. The most significant changes included decreased galactosylation and
sialylation of IgG (which regulate proinflammatory and antiinflammatory actions
of IgG) as well as decreased core fucose and increased bisecting
N-acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity).
CONCLUSION: The IgG glycome in SLE patients is significantly altered in a way
that decreases immunosuppressive action of circulating immunoglobulins. The
magnitude of observed changes is associated with the intensity of the disease,
indicating that aberrant IgG glycome composition or changes in IgG glycosylation
may be an important molecular mechanism in SLE.