Table 1.
Clinical significance of sialylated IgG in human autoimmune diseases
| Disease | Serum levels of sialylated IgG (s-IgG) | Clinical significance | Ref. |
|---|---|---|---|
| Rheumatoid arthritis (RA) | Total s-IgG↓ RF s-IgG↓ ACPA s-IgG↓ |
Enhanced diagnostic sensitivity: Sulfated FA2G2S1 was identified as a biomarker to distinguish RA patients from the ACPA and RF-negative ones with high sensitivity Therapeutic response: Serum s-IgG was significantly elevated after methotrexate therapy in RA patients; Negative correlations of s-IgG were observed between DAS 28 and Sambucus nigra before and after therapy. |
9,59,65,77,78 |
| Juvenile idiopathic arthritis (JIA) | Total s-IgG↓ | Total IgG sialylation was reduced in JIA patients' sera compared with that of healthy controls | 79 |
| Systemic lupus erythematosus (SLE) | Total s-IgG↓ Anti-histone s-IgG↓ |
Three major sialylated glycans in total IgG were decreased in SLE patients of African Caribbean populations, Latin Americans of Mestizo ethnicity and Han Chinese populations Disease intensity: Monosialylated glycans in total s-IgG were negatively associated with symptom profiles of SLE patients in African Caribbean and Latin American cohorts. |
56,80 |
| Anti-phospholipid syndrome (APS) | Anti-β2GP1 s-IgG↓ |
Disease activity: A significant negative correlation was observed between BVAS score and the sialylation ratio of PR3-ANCA. Closing diagnostic gaps-asymptomatic individuals: Sera from healthy children showed the highest Sambucus nigra/anti-β2GP1 s-IgG ratio. The ratio decreased from aaPL to SLE + aPL to SAPS to PAPS. |
19,64 |
| Granulomatosis with polyangiitis (GPA) | Total s-IgG↓ PR3-ANCA s-IgG1↓ |
Total s-IgG1 and s-IgG2 were reduced in GPA patients compared to healthy controls Enhanced diagnostic specificity: PR3-ANCA s-IgG was used to determine GPA activity with higher specificity and sensitivity than nonsialylated IgG. Relapse: Patients with low total s-IgG1 were highly prone to relapse after an ANCA increases. The degree of total s-IgG1 Fc was found to differentiate relapsing patients from nonrelapsing ones with high sensitivity and specificity. |
57,64,69 |
| Kawasaki disease (KD) | Total s-IgG↓ | Therapeutic response: IVIg-resistant KD patients had lower levels of total s-IgG than IVIg-responsive KD patients at both pretreatment and one-year time points | 20 |
| Crohn's disease (CD) | Total s-IgG↓ | The proportion of total s-IgG was significantly decreased in CD patients | 58,81 |
| Fetal and neonatal alloimmune thrombocytopenia (FNAIT) | Anti-HPA-1a s-IgG1↑ | Anti-HPA-1a s-IgG1 increased up to 30% compared to total IgG sialylation of less than 10% in FNAIT patients. | 73 |
| Hemolytic disease of the fetus and newborn (HDFN) | Anti-D s-IgG↑ Anti-c s-IgG1↑ |
Disease activity: High Fc sialylation of anti-c was correlated with HDFN disease severity. | 75,82 |
| Chronic inflammatory demyelinating polyneuropathy (CIDP) | Total s-IgG Fc↓ | s-IgG Fc was reduced in CIDP patients Therapeutic response: Reduction in clinical disease severity scores upon IVIg therapy was significantly associated with an induction of s-IgG Fc. |
70,83 |
| Guillain-Barré syndrome (GBS) | s-IgG2↓ |
Therapeutic response: IVIg therapy resulted in increased s-IgG1 and s-IgG2 in GBS patients A higher level of s-IgG1 and IgG2 Fc was associated with reduced disease severity and improved outcomes of GBS patients after IVIg therapy. |
70,84 |
| Alzheimer's disease (AD) | s-IgG1↓ | S-IgG1 (FA2G2S1) was reduced in AD patients compared to patients with SMCI | 85 |
| Parkinson's disease (PD) | Total s-IgG↓ | s-IgG sialylation decreased in PD patients Disease activity: FG2S1 was negatively associated with case status, with high sensitivity and specificity. |
86 |
ACPA, anti-citrullinated protein antibody; anti-βGP1, anti-beta-2-glycoprotein 1; BVAS, Birmingham vasculitis activity score; PR3-ANCA, anti-neutrophilic cytoplasmic autoantibodies targeting proteinase 3; aPL, antiphospholipid antibody; aaPL, asymptomatic carriers of aPL; SLE + aaPL, patients with SLE without symptoms of APS harboring circulating aPL; SAPS, patients with APS and SLE as an underlying disease; PAPS, patients with primary APS; IVIg, intravenous immunoglobulin; HPA, human platelet antigen; anti-D, anti-rhesus D (RhD); SMCI, stable mild cognitive impairment.