Stepwise addition of CBCAPS and antibody components to ANA, anti-dsDNA and anti-Sm serologies
| Model #1 | Model #2: model #1+specificity component | Model #3: model #1+CBCAPS | Model #4: model #1+CBCAPS+specificity component | |
|---|---|---|---|---|
| Tier1 | dsDNA; Sm | dsDNA; Sm | dsDNA; Sm; EC4d; BC4d | dsDNA; Sm; EC4d; BC4d |
| Tier 2 | ANA* | ANA*+Antibody specificity† | ANA*+CBCAPS‡ | ANA*+CBCAPS‡+Antibody specificity† |
| Total sensitivity (%) | 89 | 83 | 84 | 80 |
| Total specificity (others) (%) | 53 | 76 | 70 | 86 |
| Sjogren's syndrome (%) | 12 | 61 | 52 | 70 |
| Scleroderma (%) | 34 | 77 | 57 | 91 |
| PM/DM (%) | 26 | 41 | 59 | 74 |
| RA (%) | 67 | 86 | 77 | 92 |
| Other diseases (%) | 69 | 69 | 76 | 76 |
| Specificity (NHV) (%) | 90 | 91 | 95 | 98 |
| Two-tiered AUC | 0.781 | 0.804 | 0.894 | 0.913§ |
The diagnostic methodology involved two consecutive ‘tiers’ of analysis in which the aggregated diagnostic value of anti-dsDNA, anti-Sm, ANA combined with CBCAPS (EC4d and BC4d) and antibody specificity component (positivity to either anti-MCV, SS-B/La, Jo-1, Scl-70 or CENP) (model #4 as presented figure 1) was compared with model #1.
Model#1 relied on anti-dsDNA (>301 units confirmed by Crithidia) or anti-Sm (>10 units) reactivities in tier 1. Tier 2 was determined among subjects negative in tier 1 and consisted of an index score of the ANA component only (as defined in figure 1 legend); positivity for the index score (>0) was indicative of SLE, and the two-tier combination resulted in the overall performance characteristics (total sensitivity and total specificity). The stepwise addition of CBCAPS (model #3) and the antibody specificity component (model #4) to model #1 maximised the performances characteristics.
Total sensitivity and specificity are SLE vs. all others diseases. The individual sensitivities and specificities are SLE vs. the individual disease.
*ANA component.
†Antibody specificity component.
‡CBCAPS component.
§p<0.01 vs. model 1, 2 and 3.
ANA, antinuclear antibodies; anti-Sm, anti-Smith; AUC, area under the curve; CBCAPS, complement C4 activation products; anti-dsDNA, antibodies to double-stranded DNA; PM/DM, polymyositis/dermatomyositis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; NHV, normal healthy volunteers; anti-MCV, anti-mutated citrullinated vimentin; EC4d, complement C4d levels on erythrocytes; BC4d, complement C4d levels on cells; CENP, Centromere extractable nuclear antigen; Scl, scleroderma; SS, Sjogren's syndrome.