GC6 Antibody
Description
GC6 Cohort and Antibody Profiling
The GC6 cohort focuses on identifying biomarkers of TB progression, particularly through antibody responses. Key findings include:
SeroScore: A Multivariate Antibody Signature
A SeroScore was developed to predict TB progression using Mycobacterium tuberculosis (Mtb)-specific antibody features. In the GC6 cohort, this score was validated in adolescents and adults, with performance varying by age and sex .
| SeroScore Components | Antigen Specificity | Class/Subclass |
|---|---|---|
| PPD-specific IgG2 | Purified Protein Derivative (PPD) | IgG2 |
| PPD-specific IgA1 | PPD | IgA1 |
| PPD-specific IgA2 | PPD | IgA2 |
| IgM | Non-specific | IgM |
| FcγR3B binding | Fc receptor | FcγR3B |
| LAM-specific IgG1 | Lipoarabinomannan (LAM) | IgG1 |
| ESAT6-specific IgG2 | Early Secretory Antigen 6 (ESAT6) | IgG2 |
Source: Derived from LASSO analysis in GC6 cohort .
Performance of SeroScore in GC6 Cohort
The SeroScore demonstrated longitudinal stability in predicting TB progression, particularly in adolescents.
| Time Window (Months Before Diagnosis) | AUC (GC6 Cohort) | Demographic Group | AUC |
|---|---|---|---|
| 0–9 | 0.72–0.73 | Adolescents (8–20 yrs) | 0.82 |
| 9–18 | 0.72–0.73 | Adults (21–60 yrs) | 0.69 |
| 18–27 | 0.72–0.73 | Combined | 0.72–0.73 |
Note: AUC = Area Under the Curve. Higher AUC indicates better predictive accuracy .
Age-Related Changes
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Class-switched antibodies (IgG2, IgG3, IgA1) increase with age in non-progressors, reflecting chronic Mtb exposure .
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IgM levels and Fc sialylation/galactosylation (linked to anti-inflammatory properties) decrease with age in non-progressors .
| Antibody Feature | Trend with Age | Functional Implication |
|---|---|---|
| IgG2, IgG3, IgA1 | ↑ | Pro-inflammatory, class-switched responses |
| IgM | ↓ | Reduced primary response capacity |
| Fc sialylation/galactosylation | ↓ | Reduced anti-inflammatory signaling |
Source: Mixed linear models in GC6 cohort .
Sex Differences
Comparison with RISK6 Signature
The RISK6 transcriptional signature (SERPING1, GBP2, FCGR1B, TRMT2A, SDR39U1, TUBGCP6) and SeroScore captured distinct immunological processes .
| Metric | SeroScore | RISK6 | Combined |
|---|---|---|---|
| AUC (Full Cohort) | 0.82 | 0.82 | 0.86 |
| AUC (0–9 Months) | 0.79 | 0.86 | 0.86 |
| AUC (18–27 Months) | 0.86 | 0.67 | 0.86 |
Key Insight: SeroScore remained stable over time, while RISK6 performance declined in later time windows .
Implications for TB Diagnostics and Therapeutics
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Early Detection: The SeroScore identified progressors up to 2 years before diagnosis, outperforming RISK6 in longitudinal stability .
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Targeted Interventions: Adolescents and males may benefit more from antibody-based diagnostics, suggesting population-specific strategies .
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Mechanistic Insights: Class-switched antibodies and Fc receptor binding patterns highlight pathways for therapeutic modulation (e.g., targeting IgA1 or FcγR3B) .
Limitations and Future Directions
Product Specs
**Constituents:** 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- MAG4 facilitates the transport of storage protein precursors from the ER to the Golgi complex during seed maturation. PMID: 20837504
