Changes in anti-thyroglobulin IgG glycosylation patterns in Hashimoto's thyroiditis patients.
OBJECTIVE
Sera of Hashimoto's thyroiditis (HT) patients are known to exhibit elevated levels of anti-thyroglobulin IgG (TgAb IgG). Therefore, TgAb IgG represents a hallmark of this debilitating autoimmune disease. The aim of our study was to investigate the differential expression of specific glycosylation patterns of TgAb IgG from HT patients and healthy blood donors.


METHODS
HT patients (n = 32) were divided into two subgroups, medium level group (mHT, n = 15) and high level group (hHT, n = 17), according to the serum levels of TgAb detected by electrochemiluminescence immunoassay. TgAb IgG was purified by affinity chromatography from the sera of the HT group and control group (n = 15). MALDI-QIT-TOF-MS/MS spectrometry was performed to identify the glycosylation profiles of purified TgAb IgG. Lectin microarray technology was used to compare the abundance of different glycans found on TgAb IgG between HT patients and controls, and between the mHT and hHT groups.


RESULTS
The results by MALDI-QIT-TOF-MS/MS showed that the glycosylation profiles of TgAb IgG were similar between the mHT, hHT, and control groups. Furthermore, the lectin microarray showed that compared to the control group (all P < .001), there were higher levels present of (1) mannose (detected as lectin LCA, VFA, and MNA-M); (2) terminal sialic acid (detected as SNA-I and PSA); (3) core fucose (detected as LcH); and (4) Gal(β1-4)GlcNAc(β1-2)Man glycans (detected as PHA-L) on TgAb IgG from the HT group. A similar trend was observed between the hHT and mHT group, with elevated levels of mannose, terminal sialic acid, core fucose, and Gal(β1-4)GlcNAc(β1-2)Man glycans on TgAb IgG found in the hHT group compared with the mHT group (all P < .05).


CONCLUSIONS
TgAb IgG of HT patients exhibits higher glycosylation levels than those observed for TgAb IgG of healthy controls. Our results provide new clues for exploring the role of TgAb in the pathogenesis of HT.
Department of Endocrinology (S.Y., Y.Z., Yal.L., N.Y., H.Z., G.L., Ya.G., Yi.G., X.G.), Peking University First Hospital, Beijing 100034, China; Institute of Biophysics (Q.L., C.H., H.W., Yan.L.), Chinese Academy of Sciences, Beijing 100101, China.
Shanshan
S
Yuan
Qianqian
Q
Li
Yang
Y
Zhang
Chuncui
C
Huang
Hongmei
H
Wu
Yan
Y
Li
Yalei
Y
Liu
Nan
N
Yu
Hong
H
Zhang
Guizhi
G
Lu
Yanming
Y
Gao
Ying
Y
Gao
Xiaohui
X
Guo
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D050031:Hashimoto Disease / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013954:Thyroglobulin / Q000276:immunology*; D006023:Glycoproteins
D001323:Autoantibodies; D007074:Immunoglobulin G; D013954:Thyroglobulin; C006606:anti-thyroglobulin; C046179:glycosylated IgG; D006023:Glycoproteins