Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: A critical review

Herein we will review the role of glycans in the immune system. Specific topics covered include: the glycosylation sites of IgE, IgM, IgD, IgE, IgA, and IgG; how glycans can encode “self” identity by functioning as either danger associated molecular patterns (DAMPs) or self-associated molecular patterns (SAMPs); the role of glycans as markers of protein integrity and age; how the glycocalyx can dictate the migration pattern of immune cells; and how the combination of Fc N-glycans and Ig isotype dictate the effector function of immunoglobulins. We speculate that the latter may be responsible for the well-documented association between alterations of the serum glycome and autoimmunity. Due to technological limitations, the extent of these autoimmune-associated glycan alterations and their role in disease pathophysiology has not been fully elucidated. Thus, we also review the current technologies available for glycan analysis, placing an emphasis on Multiple Reaction Monitoring (MRM), a rapid high-throughput technology that has great potential for glycan biomarker research. Finally, we put forth The Altered Glycan Theory of Autoimmunity, which states that each autoimmune disease will have a unique glycan signature characterized by the site-specific relative abundances of individual glycan structures on immune cells and extracellular proteins, especially the site-specific glycosylation patterns of the different immunoglobulin(Ig) classes and subclasses.     

Diagnostic Value of Positive Findings of Toxoplasma gondii-Specific Immunoglobulin M Serum Antibody in Uveitis Patients to Confirm Ocular Toxoplasmosis

Purpose: To assess the value of positive immunoglobulin (Ig) M serum antibody (Ab) findings in uveitis patients.

Methods: We reviewed medical records of patients who had a positive serological test for Toxoplasma gondii-specific IgM Ab. Their clinical data, including history, demographic characteristics, laboratory findings, clinical findings, treatment outcomes, and recurrences, were reviewed retrospectively.

Results: Of 2919 uveitis patients who underwent a serological test for suspected ocular toxoplasmosis (OT), 18 presented with positive Ig M results. All 18 patients (100.0% specificity) were clinically diagnosed with OT. None had any retinochoroidal scar at the initial visit, indicating the OT was a recent and primary infection. However, 15 patients (83.3%) had no history suspected to account for the Toxoplasma transmission.

Conclusions: The T. gondii IgM serum Ab is a specific biomarker for diagnosis of primary OT. Epidemiological studies are warranted to investigate the non-classic transmission routes of T. gondii in OT.     

Clinical significance and pathological features of ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis

Objective To investigate the clinical significance and pathological features of lymphocytes and plasma cells infiltration and related ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis (IgG4-TIN). Methods Complete data was collected from 24 patients with IgG4-TIN confirmed by pathology in the Peking University First Hospital. The renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy examination. In addition, immunohistochemistry was used to detect the distribution of CD20+ B lymphocytes, CD3+ T lymphocytes and CD138+ plasma cells. Results A total of 24 patients were enrolled in the study, including 21 males (87.5%), 3 females (12.5%). The age was (58.0±10.8) years (38-75 years). Pathology analysis showed ectopic lymphoid-like structures were located in 16 (66.7%) cases and Russell bodies were detected in infiltrative plasma cells of 19(79.2%) cases with IgG4-TIN. Compared with cases without Russell body formation, cases with Russell body formation in renal interstitial plasma cells were more prone to show ectopic germinal center-like structure formation (P=0.001), tubular basement membrane (TBM) electron dense deposits (P=0.040) and reduced blood C3 levels (P=0.028). Conclusions Abnormal tubulointerstitial infiltration of ectopic lymphoid-like structures and plasma cells with prominent Russell body exist in IgG4-TIN patients, which suggests the persistent activation of lymphocytes and plasma cells in renal interstitium may contribute to the pathogenesis of IgG4-TIN.     

Immunoglobulin G4-positive staining of orbital lesions in thyroid eye disease: Report of two cases

We report two cases with immunoglobulin G4 (IgG4)-positive staining of orbital lesions and thyroid eye disease (TED). Case 1 was a 63-year-old male with right upper eyelid swelling due to right lacrimal gland enlargement. Case 2 was a 49-year-old male with bilateral proptosis due to multiple orbital masses. Both the biopsied right lacrimal gland in Case 1 and the orbital masses on both sides in Case 2 showed infiltration of immunoglobulin-G4-positive plasma cells.     

B细胞激活因子与过敏性紫癜相关性研究

目的:通过分析B细胞激活因子(BAFF)与患者免疫球蛋白在不同类型过敏性紫癜(HSP)中的表达,初步探讨BAFF在过敏性紫癜免疫发病机制中的作用。方法:收集HSP活动期患者,包括皮肤型30例、关节型30例、腹型32例、肾型31例、混合型41例,将健康人40例作为对照组。速率散射比浊法测定免疫球蛋白水平;ELISA方法检测BAFF蛋白含量。结果:IgA仅在混合型HSP中增高,IgG和IgM在各组中并无增高;不同类型HSP活动期患者血清中BAFF表达水平均明显高于对照组;混合型HSP患者血清中BAFF表达水平与同型患者IgA表达水平呈中等程度的相关性。结论:BAFF与HSP发病时的体液免疫增强有关。     

食管癌中特异表达的人类omega蛋白(Igll3)基因的序列分析及意义

目的筛选食管癌中差异表达的基因,进一步了解食管癌发生的分子机制。方法利用荧光差异显示技术(DD-PCR)从食管癌组织相对癌旁组织中获得差异表达片段,对这些片段进行克隆和序列分析。通过在GenBank中同源性检索,查找差异片段相对应的同源基因。利用定量PCR检测验证该基因表达的差异性。设计引物获得该基因全长。结果通过DD-PCR得到3个差异片段,分别为人类10号常染色体上的开放阅读框99;人类信号转导和激活转录因子2及人类omega蛋白(Igll3)。定量PCR验证的结果表明,Igll3在食管癌组织中的表达量高于癌旁组织。设计引物得到该基因全长,测序表明该基因长为711bp,编码236aa。结论 Igll3在食管癌组织中异常表达,可能在食管癌发生过程中起着重要的作用。     

A case of Mikulicz’s disease with Th2-biased cytokine profile: possible feature discriminable from Sjögren’s syndrome

Abstract

This article concerns a male patient with Mikulicz’s disease (MD) accompanied with marked elevation of serum immunoglobulin (Ig)G4 and IgE levels. His peripheral blood mononuclear cells (PBMC) showed markedly enhanced in vitro production of interleukin (IL)-4, IL-5, IL-13, but not interferon gamma (IFN-γ) compared with patients with Sjögren’s syndrome (SS) and healthy donors, suggesting distinct Th2 bias in this MD patient. Besides the prominent infiltration of IgG4-producing plasma cells, the enhanced expression of both CD40 and CD40 ligand (CD40L) were observed in the swollen salivary gland of the MD patient, suggesting enhanced signaling pathways for the induction of IgG4 and IgE switching. Possible differences between MD and SS in light of their underlying pathogenesis are discussed.     

乙肝免疫球蛋白联合乙肝疫苗阻断乙肝感染父婴传播的可行性分析

目的观察乙肝疫苗与乙肝免疫球蛋白联合应用对乙肝感染父婴传播阻断的临床效果。方法2012年1月至2015年5月在湛江中心人民医院分娩的产妇及其配偶68对为研究对象,产妇均未感染乙肝病毒,配偶均为乙肝患者,随机分为观察组和对照组各34对。对照组新生儿注射乙肝疫苗,观察组在对照组基础上加用乙肝免疫球蛋白。观察两组新生儿出生体质量、Apgar评分、丙氨酸氨基转移酶(ALT)水平及乙型肝炎病毒(HBV)检测结果。结果两组新生儿出生体质量、Apgar评分以及ALT水平比较差异无统计学意义(P0.05);观察组新生儿HBsAg阳性率为5.88%(2/34),低于对照组23.53%(8/34),差异有统计学意义(P0.05);观察组新生儿HBsAb阳性率为32.35%(11/34),高于对照组11.76%(4/34),差异有统计学意义(P0.05)。结论新生儿应用乙肝疫苗联合乙肝免疫球蛋白,能够对感染乙肝病毒的父婴传播进行有效阻断,明显降低新生儿感染率。