Clinical diagnoses in patients tested for antinuclear antibodies (ANAs)
| Disease | IIF negative | IIF 1:80 | IIF 1:160 | IIF 1:320 | IIF 1:640 | IIF ≥1:1280 | IIF SSA | Total |
| SLE (newly diagnosed) | 3 (1,0,2) | 1 (0,1,0) | 2 (1,0,1) | 6 (1,0,5) | 3 (0,0,3) | 15 | ||
| SLE (established) | 8 (2,0,6) | 6 (2,1,3) | 14 (8,0,6) | 11 (4,2,5) | 7 (2,0,5) | 6 (0,0,6) | 16 (0,0,16) | 68 |
| SLE (not fulfilling classification criteria) | 6 (3,2,1) | 2 (0,0,2) | 2 (2,0,0) | 1 (0,0,1) | 1 (1,0,0) | 3 (1,1,1) | 5 (0,0,5) | 20 |
| Cutaneous lupus | 4 (4,0,0) | 3 (1,0,2) | 4 (2,0,2) | 1 (1,0,0) | 10 (0,0,10) | 22 | ||
| Systemic sclerosis (newly diagnosed) | 3 (1,0,2) | 5 (0,0,5) | 9 (2,0,7) | 19 (3,0,16) | 36 | |||
| Systemic sclerosis (established) | 5 (1,0,4) | 5 (1,1,3) | 11 (0,0,11) | 6 (1,0,5) | 27 | |||
| Systemic sclerosis (not fulfilling classification criteria) | 1 (0,1,0) | 3 (3,0,0) | 1 (0,0,1) | 2 (0,0,2) | 4 (0,0,4) | 2 (1,0,1) | 1 (0,0,1) | 14 |
| Polymyositis/dermatomyositis (newly diagnosed) | 2 (0,0,2) | 1 (0,0,1) | 2 (1,1,0) | 2 (1,0,1) | 2 (0,0,2) | 9 | ||
| Polymyositis/dermatomyositis (established) | 1 (1,0,0) | 2 (1,1,0) | 1 (0,0,1) | 3 (1,1,1) | 1 (0,0,1) | 8 | ||
| Polymyositis/dermatomyositis (not fulfilling classification criteria) | 2 (0,0,2) | 1 (0,1,0) | 2 (2,0,0) | 4 (3,0,1) | 2 (0,0,2) | 1 (0,0,1) | 12 | |
| Sjögren’s syndrome (newly diagnosed) | 4 (0,0,4) | 1 (0,0,1) | 1 (0,0,1) | 13 (0,0,13) | 19 | |||
| Sjögren (established) | 2 (0,1,1) | 2 (2,0,0) | 1 (0,0,1) | 3 (0,0,3) | 1 (0,0,1) | 1 (0,0,1) | 16 (0,0,16) | 26 |
| Sjögren (not fulfilling classification criteria) | 2 (1,1,0) | 1 (1,0,0) | 1 (0,0,1) | 4 | ||||
| Mixed connective tissue disease (newly diagnosed) | 4 (0,0,4) | 4 | ||||||
| Mixed connective tissue disease (established) | 1 (0,0,1) | 1 (0,0,1) | 2 (0,0,2) | 4 | ||||
| Mixed connective tissue disease (not fulfilling classification criteria) | 1 (0,1,0) | 3 (0,0,3) | 4 | |||||
| Not differentiated (doubtful) | 1 (1,0,0) | 3 (3,0,0) | 2 (1, 1) | 1 (1,0,0) | 1 (0,0,1) | 8 | ||
| Non-AASRD | 47 (30,3,14) | 30 (22,0,8) | 18 (17,01) | 8 (6,0,2) | 2 (1,0,1) | 2 (2,0,0) | 3 (0,0,3) | 110 |
| Rheumatic disease | 49 (25,11,13) | 42 (37,1,4) | 52 (48,0,4) | 23 (20,1,2) | 6 (5,1,0) | 4 (4,0,0) | 7 (0,0,7) | 183 |
| Inflammatory disease | 76 (39,15,22) | 64 (54,4,6) | 44 (37,2,5) | 27 (3,15,9) | 12 (10,1,1) | 12 (10, , 2) | 6 (0,0,6) | 241 |
| No inflammatory disease | 655 (395,96,164) | 439 (399,10,30) | 332 (296,13,23) | 109 (92,9,8) | 43 (33,4,6) | 29 (18,1,10) | 34 (4,2,28) | 1641 |
| Total | 859 (500,130,229) | 594 (521,17,56) | 488 (419,16,53) | 207 (145,19,43) | 104 (56,5,43) | 105 (42,4,59) | 118 (4,2,112) | 2475 |
| Positive predictive values (PPVs) | ||||||||
| PPV of IIF for SLE | 0.001 | 0.010 | 0.035 | 0.058 | 0.087 | 0.118 | 0.168 | |
| PPV of IIF/EliA(−) SLE | 0.004 | 0.022 | 0.028 | 0.055 | 0.024 | |||
| PPV of IIF/EliA(+)* SLE | 0.056 | 0.116 | 0.131 | 0.125 | 0.180 | 0.174 | ||
| PPV of IIF for AASRD | 0.020 | 0.069 | 0.157 | 0.344 | 0.515 | 0.541 | ||
| PPV of IIF/EliA(−) for AASRD | 0.010 | 0.034 | 0.057 | 0.109 | 0.150 | |||
| PPV of IIF/EliA(+)* for AASRD | 0.040 | 0.100 | 0.284 | 0.404 | 0.659 | 0.772 | 0.562 | |
| PPV of IIF/EliA(+)† for AASRD | 0.058 | 0.111 | 0.365 | 0.447 | 0.750 | 0.796 | 0.573 | |
| Estimated likelihood ratios (LRs) | ||||||||
| Estimated LR of IIF for SLE | 0.096 | 1.2 | 4.1 | 7.0 | 10.9 | 15.1 | 23.0 | |
| Estimated LR of IIF/EliA(−) for SLE | 0.44 | 2.5 | 3.2 | 6.6 | 2.8 | |||
| Estimated LR of IIF/EliA(+) for SLE | 6.8 | 14.9 | 17.1 | 16.2 | 25.0 | 24.0 |
9851 consecutive patients were tested for ANA by indirect immunofluorescence (IIF) (HEp-2000; ImmunoConcepts) and by solid phase (EliA CTD screen, detecting antibodies to dsDNA, SSA/Ro 52, SSA/Ro 60, SSB/La, U1-RNP (RNP-70, A, C), Sm, Jo-1, Scl-70, CENP, fibrillarin, RNA Pol III, PM-Scl, Mi-2, Rib-P and PCNA). The table gives an overview of the clinical diagnoses and the test results in consecutive patients who tested positive for ANA by IIF and/or CTD screen and in a selection on 500 patients who tested negative by both assays (total n=2475; 325 patients were excluded because there were insufficient data for proper clinical categorisation). The values indicate the number of patients with a particular IIF result. The values in parentheses indicate the number of patients who tested negative (first number), equivocal (second number) or positive (third number) with CTD screen. The population has been described in Willems et al.7 Non-AASRD (non-ANA-associated systemic rheumatic disease) includes, for example, different types of vasculitis, polymyalgia rheumatica and sarcoidosis. Rheumatic diseases include, for example, rheumatoid arthritis and psoriatic arthritis. Inflammatory diseases include, for example, colitis ulcerosa, Crohn’s disease, autoimmune hepatitis, autoimmune thyroiditis, psoriasis and immune thrombocytopenic purpura.
Newly diagnosed: tested on a diagnostic sample (ie, at the time of diagnosis).
Established: tested on a follow-up sample (most of these patients had received immunosuppressive therapy and had been diagnosed in another centre).
Not fulfilling classification criteria: the clinician strongly considered the presence of an AASRD and initiated immunosuppressive therapy, but the patient did not fulfil the classification criteria. For description of the classification criteria, see Willems et al.7
For the estimation of the PPV of a negative IIF result for systemic lupus erythematosus (SLE), we only took into account the SLE cases documented (1) in the patients who were single positive for CTD screen and (2) in a selection of 500 patients who were negative for IIF and CTD screen. This probably is an underestimation as we did not check the medical records of all double-negative patients. Patients with AASRD were checked whether they fulfilled the classification criteria of Sjögren’s syndrome, systemic sclerosis, dermatomyositis/polymyositis, mixed connective tissue disease and SLE as described in Willems et al.7 For estimation of the PPV, we excluded patients who did not fulfil the classification criteria. For estimation of the PPV for AASRD, we included cutaneous lupus as an AASRD.
*Including equivocal results.
†Excluding equivocal results.