分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: 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(beta 1-4) GlcNAc(beta 1-2) 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(beta 1-4) GlcNAc(< 12) 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.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-05
摘要: Growing evidence indicates that B cells are not the only source of immunoglobulin (Ig). To investigate this discovery further, we used mu MT mice, which have a disruption of the first transmembrane exon of the mu heavy chain and do not express the membrane form of IgM. These mice lack mature B cells and thus serve as a good model to explore Ig expression by liver epithelial cells. We found that Ig heavy chains (mu, delta, gamma and alpha) and light chains (kappa and lambda) were expressed in sorted liver epithelial cells of mu MT mice. Surprisingly, each heavy chain class showed its respective variable region sequence characteristics in their variable region, instead of sharing the same VDJ usage, which suggests that class switching does not occur in liver epithelial cells. Moreover, the gamma and alpha chains, but not the mu and delta chains, showed mutations in the variable region, thus indicating that different classes of Ig have different activities. Our findings support the concept that non-B cells, liver epithelial cells here, can produce different classes of Ig.