Vasculitis & polymyalgia rheumatica
Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants
Authors' conclusion
We confirmed the utility of plasma ADA2 activity as a diagnostic assay and showed that the inflammatory phenotype of DADA2 occurred in cases with residual activity.
Study context
- Population
- Individuals who underwent ADA2 testing from 2018 to 2025; international cohort of DADA2 casesDADA2 cases
- Participants
- 200 individuals
- Comparison
- Plasma ADA2 activity in genetically confirmed DADA2 cases vs controls and vs carriers
- DADA2n = 200
- Outcome
- Diagnostic utility (sensitivity and specificity) of plasma ADA2 enzyme activity assay
Methodological detailsinternational cohort, in vitro analysis of ADA2 variants in transfected cells, Plasma ADA2 activity by established spectrophotometric assay; variants analysed by enzyme assay and western blotting in transfected cells
- International cohort
- In vitro analysis of ADA2 variants in transfected cells
- Plasma ADA2 activity by established spectrophotometric assay; variants analysed by enzyme assay and western blotting in transfected cells
Performance
As reported in the abstract
| Test or model | Sensitivity | Specificity |
|---|---|---|
| DADA2 vs Controls | 99.0% | 99.7% |
| DADA2 vs Carriers | 96.0% | 98.8% |
Sensitivity
DADA2 vs Controls99.0%
DADA2 vs Carriers96.0%
Specificity
DADA2 vs Controls99.7%
DADA2 vs Carriers98.8%
Further findings
- DADA2 with detectable residual ADA2 activity
- 9% · 18 of 200
DADA2 with detectable residual ADA2 activity
- Includes several cases with levels seen in carriers
Residual ADA2 activity and phenotype
- Associated with vasculitis/inflammatory phenotype but not with disease severity
Hypomorphic missense variant (>20% residual ADA2 function in 293T cells) among cases with residual activity
- Cases with ≥1 hypomorphic missense variant, of 18 with residual plasma activity, often in trans with a more deleterious variant
- 14
In vitro: missense ADA2 variants
- Variable dominant-negative effects via large intracellular protein aggregates from disulfide bond formation at Cys408
Original publication
Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants. Arthritis Rheumatol. Published 25 December 2025. doi:10.
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