Rheumatology serologies: what to order and what it means
Pick the presentation to get the panel that fits and what not to order, or enter results to see what they mean in this patient. A positive test in a patient without the matching features is often a false or bystander positive. Adults only.
1Mode
Results entered in Interpret are kept when you switch to Order; a note there counts them and offers a Clear button. The clinical picture and ANA carry across both modes.
2Clinical picture tick all that apply
Red flags
Context
Anticoagulant now needed for lupus anticoagulant
3ANA, if already done
HEp-2 indirect immunofluorescence. Titers do not apply to solid-phase ANA screens.
4Other results
Leave a test at “Not done” if it was not sent. Blank is never read as negative.
Lupus, Sjögren, MCTD
Scleroderma
Myositis
Rheumatoid arthritis
Vasculitis
Antiphospholipid
Inflammation, spondyloarthritis
How it works
Pre-test probability, in one paragraph
A test result changes the odds you started with; it does not replace them. Post-test odds = pre-test odds × likelihood ratio. When the pre-test probability is low, even a specific test produces more false positives than true positives. Example with the anti-CCP likelihood ratio from Nishimura 2007 (LR+ 12.46): at a 2% pre-test probability a positive result gives about 20%; at 30% it gives about 84%. ANA is the extreme case: 13.3% of healthy adults are positive at 1:80 (Tan 1997), and SLE is rare, so most positive ANAs in people without lupus features are not lupus. See the likelihood ratios guide.
Classification criteria are not diagnostic criteria
The ACR/EULAR criteria for RA (2010), SLE (2019), Sjögren (2016), systemic sclerosis (2013), myositis (2017), APS (2023) and GCA (2022) were built to select uniform patients for studies. This tool quotes their antibody weights because they show how much each result counts, not to label a patient. A patient can have the disease without meeting criteria, and meet criteria without having it. The PMR 2012 paper says so directly: the criteria “are not meant for diagnostic purposes.”
ANA titer and ICAP pattern
| HEp-2 titer | Healthy adults positive (Tan 1997) |
|---|---|
| 1:40 | 31.7% |
| 1:80 | 13.3% |
| 1:160 | 5.0% |
| 1:320 | 3.3% |
ICAP advises that, except for the centromere pattern (AC-3), each pattern needs an antigen-specific test before it is tied to a disease. The dense fine speckled pattern (AC-2) points away from systemic autoimmune disease only when the antibody is confirmed as anti-DFS70 and no other ENA antibody is present. Anti-SSA/Ro (Ro60), anti-Jo-1 and other myositis antibodies can be missed on HEp-2 screening, and cytoplasmic patterns may be reported as ANA-negative depending on the laboratory.
Antiphospholipid rules (2023 ACR/EULAR)
Laboratory points need at least one positive aPL within 3 years of a clinical criterion, and 3 or more points in both the clinical and the laboratory domains. Lupus anticoagulant: 1 point for a single positive, 5 for persistent. Anticardiolipin or anti-β2-glycoprotein I by ELISA, persistent: IgM moderate or high 1; IgG moderate (40–79 units) 4; IgG high in one 5; IgG high in both 7. Persistent means positive on 2 occasions at least 12 weeks apart. Moderate is 40–79 units and high is 80 units or more (Methods and Table 3 footnote; Table 1 prints “>80”, but 80 cannot be moderate). Lupus anticoagulant results taken on anticoagulation count only if a laboratory LA expert reviews and confirms them.
Not covered
- Children and adolescents (ANA in JIA, uveitis screening): adults only.
- IgG4, cryoglobulin typing, aldolase, CH50, anti-histone, anti-ribosomal P, anti-C1q, Ro52 versus Ro60, anti-PM/Scl, anti-Th/To, anti-U3-RNP, anti-SAE, anti-Ku, anti-mitochondrial and liver antibodies.
- ICAP patterns other than those listed (AC-6, AC-7, AC-11 to AC-28, mixed patterns): read them with your laboratory.
- Interpreting hepatitis B and C, HIV or parvovirus results (the tool says when to send hepatitis serology, not how to read it); Lyme testing beyond the Choosing Wisely limit.
- Anti-GBM titer levels and assay differences, kidney biopsy reading, and urine sediment.
- Treatment of any disease named here. For anticoagulation in APS, use the VTE treatment tool.
- Cancer screening details for myositis antibodies (see IMACS 2023), and fetal echocardiography schedules for anti-SSA/Ro pregnancies (see ACR 2020 reproductive health guideline).
- Crystal arthritis and synovial fluid analysis.
Versions and what was left out
Checked 21 October 2026 (revised after an independent audit): EULAR 2025 PMR/large-vessel vasculitis recommendations (published July 2026) for GCA timing; ACR 2021 GCA guideline; KDIGO 2024 ANCA vasculitis with the KDOQI 2026 US commentary; 2017 and 2020 ANCA testing consensus statements; EULAR 2023 systemic sclerosis update; ACR/CHEST 2023 ILD guidelines; 2023 ACR/EULAR APS criteria; ISTH 2020 lupus anticoagulant guidance. Also KDIGO 2021 glomerular diseases and KDIGO 2022 hepatitis C in CKD for hepatitis and cryoglobulin testing. Infection mimics of ANCA vasculitis (endocarditis, hepatitis C, tuberculosis) and ANCA-inducing drugs are sourced to Bossuyt 2017 p. 690 and KDOQI 2026. Still expert opinion: cryoglobulin testing for purpura or neuropathy without kidney involvement. Left out because they could not be verified: pooled ANCA sensitivity figures, complement causes other than SLE, aldolase, any fetal monitoring schedule, and the BSR 2006 recommendation grades.
Sources
- Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997;40(9):1601–11 (HEp-2 IIF, 15 laboratories: positive in 31.7% at 1:40, 13.3% at 1:80, 5.0% at 1:160, 3.3% at 1:320). doi:10.1002/art.1780400909
- Damoiseaux J, Andrade LEC, Carballo OG, et al. Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective. Ann Rheum Dis 2019;78(7):879–89 (Tables 1–2, AC-1 to AC-29). doi:10.1136/annrheumdis-2018-214436
- Aringer M, Costenbader K, Daikh D, et al. 2019 EULAR/ACR classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 2019;71(9):1400–12 (Table 1 definitions, Table 2 weights; ANA ≥1:80 entry criterion, sensitivity 97.8% by meta-regression). doi:10.1002/art.40930
- American College of Rheumatology. Choosing Wisely: Five things physicians and patients should question, 21 February 2013 (#1 ANA sub-serologies; #2 Lyme testing). ACR pediatric rheumatology Choosing Wisely list, 2013: “Don’t repeat a confirmed positive ANA in patients with established JIA or SLE” (as reported by Ullman K, The Rheumatologist, 1 November 2013; secondary).
- Choosing Wisely Canada / Canadian Rheumatology Association. Nine tests and treatments to question in rheumatology, version 4.0, May 2025 (#1 ANA screening, #2 HLA-B27, #9 RF and ACPA).
- American Society for Clinical Pathology. Choosing Wisely recommendation on ESR versus CRP (as reported by Medical Laboratory Observer, 9 February 2015; secondary).
- Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 2007;146(11):797–808 (pooled anti-CCP sensitivity 67%, specificity 95%, LR+ 12.46, LR− 0.36; IgM RF 69%, 85%, 4.86, 0.38). doi:10.7326/0003-4819-146-11-200706050-00008
- Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an ACR/EULAR collaborative initiative. Arthritis Rheum 2010;62(9):2569–81. doi:10.1002/art.27584. Serology footnote checked against two reprints (Arch Rheumatol 2020;35:592, Table 2; ebm.one), both secondary; both drop the ≤/> symbols.
- Bossuyt X, Cohen Tervaert JW, Arimura Y, et al. Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol 2017;13(11):683–92 (Box 1 recommendation 3, p. 689: other immunoassays and/or IIF, or an experienced laboratory, when both are negative and suspicion stays strong; p. 690 explanatory text, not a numbered statement: infective endocarditis, hepatitis C and tuberculosis should be excluded; levamisole-adulterated cocaine, hydralazine, propylthiouracil and minocycline). doi:10.1038/nrrheum.2017.140
- KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021;100(4S):S1–S276 (Practice Point 1.8.2: screen for TB, HBV, HCV, HIV and syphilis in clinically appropriate patients; Practice Point 7.2.2.1.1: test for HBV in proteinuric glomerular disease). doi:10.1016/j.kint.2021.05.021
- KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in CKD. Kidney Int 2022;102(6S):S129–S205 (Recommendation 1.1.1, 1C: screen for HCV at initial CKD evaluation; Recommendation 5.1 and Figure 4: hematuria, low C4, circulating cryoglobulins, systemic signs of cryoglobulinemia and rheumatoid factor mark typical HCV-associated glomerulonephritis). doi:10.1016/j.kint.2022.07.013
- Chung SA, Langford CA, Maz M, et al. 2021 ACR/Vasculitis Foundation guideline for the management of ANCA-associated vasculitis. Arthritis Rheumatol 2021;73(8):1366–83 (background: GPA with PR3, MPA with MPO, about 40% of EGPA ANCA-positive). doi:10.1002/art.41773
- KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis. Kidney Int 2024;105(3S):S71–S116 (Practice Point 9.1.1; Figure 1 biopsy strategy; Figure 3 RPGN work-up: ANCA, ANA, anti-GBM, complement, exclude infection; anti-GBM text). doi:10.1016/j.kint.2023.10.008
- Almaani S, Ayoub I, Geetha D. KDOQI US commentary on the KDIGO 2024 clinical practice guideline for the management of ANCA-associated vasculitis. Am J Kidney Dis 2026;87(5):597–609 (drug-induced AAV: hydralazine, propylthiouracil, levamisole-adulterated cocaine, minocycline; ANCA-positive endocarditis-associated glomerulonephritis). doi:10.1053/j.ajkd.2025.12.002
- Moiseev S, Cohen Tervaert JW, Arimura Y, et al. 2020 international consensus on ANCA testing beyond systemic vasculitis. Autoimmun Rev 2020;19(9):102618 (abstract: PR3/MPO testing in anti-GBM disease, idiopathic interstitial pneumonia and endocarditis with nephritis). doi:10.1016/j.autrev.2020.102618. (Verified this session.)
- McGrath MM, Isakova T, Rennke HG, et al. Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease. Clin J Am Soc Nephrol 2011;6(12):2799–805 (30 cases: all MPO-ANCA, 50% also PR3-ANCA). doi:10.2215/CJN.03440411
- Kumar B, Strouse J, Swee M, et al. Hydralazine-associated vasculitis: overlapping features of drug-induced lupus and vasculitis. Semin Arthritis Rheum 2018;48(2):283–7 (12 patients: all ANA and anti-histone positive, 11 MPO-ANCA, 11 anti-dsDNA). doi:10.1016/j.semarthrit.2018.01.005
- Barbhaiya M, Zuily S, Naden R, et al. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol 2023;75(10):1687–702, doi:10.1002/art.42624; co-published Ann Rheum Dis 2023;82:1258–70 (laboratory domains 7–8: moderate 40–79 units, high ≥80 units in the Methods and Table 3 footnote; persistence rule; LA testing notes). Read from the author repository copy (archive-ouverte.unige.ch).
- Tripodi A, Cohen H, Devreese KMJ. Lupus anticoagulant detection in anticoagulated patients: ISTH SSC guidance. J Thromb Haemost 2020;18(7):1569–75 (DOACs: LA detection not recommended; VKA: dilution into normal plasma not reliable; some reagents neutralize UFH or LMWH up to 1.0 U/mL). PMID 32619349. Devreese KMJ, et al. ISTH SSC update of the guidelines for lupus anticoagulant detection and interpretation. J Thromb Haemost 2020;18(11):2828–39, doi:10.1111/jth.15047; LMWH 12 h timing taken from Favaloro EJ, Pasalic L. Res Pract Thromb Haemost 2022;6(2):e12676, Table 2 (secondary).
- Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019;78(10):1296–304 (Box 1: high-risk profile requires positivity on 2 or more occasions at least 12 weeks apart; no rivaroxaban in triple positivity). doi:10.1136/annrheumdis-2019-215213
- Shiboski CH, Shiboski SC, Seror R, et al. 2016 ACR/EULAR classification criteria for primary Sjögren’s syndrome. Arthritis Rheumatol 2017;69(1):35–45. doi:10.1002/art.39859
- Izmirly P, Kim M, Friedman DM, et al. Hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti-SSA/Ro-positive mothers (PATCH). J Am Coll Cardiol 2020;76(3):292–302 (background risk about 2%; historical recurrence 18%; 7.4% on hydroxychloroquine). doi:10.1016/j.jacc.2020.05.045. Sammaritano LR, et al. 2020 ACR guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 2020;72(4):529–56. doi:10.1002/art.41191
- van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an ACR/EULAR collaborative initiative. Arthritis Rheum 2013;65(11):2737–47. doi:10.1002/art.38098
- Elhannani A, Martel ME, Collet A, et al. Anti-RNA polymerase III antibodies in systemic sclerosis: prevalence and clinical associations from a systematic review and meta-analysis. Rheumatology (Oxford) 2025;64(12):6023–35 (renal crisis OR 7.82; cancer OR 1.86; diffuse skin OR 2.20). doi:10.1093/rheumatology/keaf392
- Del Galdo F, Lescoat A, Conaghan PG, et al. EULAR recommendations for the treatment of systemic sclerosis: 2023 update. Ann Rheum Dis 2025;84:29–40 (renal crisis recommendations: ACE inhibitor at diagnosis, LoE 4, grade C; blood pressure monitoring on glucocorticoids, LoE 3, grade C). doi:10.1136/ard-2024-226430. Butler EA, Baron M, Fogo AB, et al. Generation of a core set of items to develop classification criteria for scleroderma renal crisis. Arthritis Rheumatol 2019;71(6):964–71. doi:10.1002/art.40809
- Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies. Arthritis Rheumatol 2017;69(12):2271–82 (without muscle biopsy: anti-Jo-1 3.9, raised CK/LDH/AST/ALT 1.3; with biopsy 3.8 and 1.4). doi:10.1002/art.40320
- Sato S, Hirakata M, Kuwana M, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 2005;52(5):1571–6 (rapidly progressive ILD 50% vs 6%). doi:10.1002/art.21023
- Mammen AL, Chung T, Christopher-Stine L, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum 2011;63(3):713–21 (92.3% of anti-HMGCR patients aged 50 or older had taken statins). doi:10.1002/art.30156
- Oldroyd AGS, Callen JP, Chinoy H, et al. International guideline for idiopathic inflammatory myopathy-associated cancer screening: an IMACS initiative. Nat Rev Rheumatol 2023;19(12):805–17 (high: anti-TIF1-γ, anti-NXP2; intermediate: anti-HMGCR, anti-Mi-2, anti-MDA5; low: anti-SRP, anti-Jo-1). doi:10.1038/s41584-023-01045-w
- Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 ACR/CHEST guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Rheumatol 2024;76(8):1201–13. doi:10.1002/art.42860. Treatment companion guideline, Arthritis Rheumatol 2024;76(8):1182–200 (rapidly progressive ILD definition). doi:10.1002/art.42861
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- Reveille JD, Hirsch R, Dillon CF, et al. The prevalence of HLA-B27 in the US: data from NHANES 2009. Arthritis Rheum 2012;64(5):1407–11 (6.1% overall; 7.5% non-Hispanic white; 3.5% all other groups combined). doi:10.1002/art.33503. Rudwaleit M, van der Heijde D, Landewé R, et al. ASAS classification criteria for axial spondyloarthritis (part II). Ann Rheum Dis 2009;68(6):777–83. doi:10.1136/ard.2009.108233
- Maz M, Chung SA, Abril A, et al. 2021 ACR/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol 2021;73(8):1349–65 (recommendations 3, 6 and 9). doi:10.1002/art.41774. Mukhtyar CB, Nikiphorou E, Bartoletti A, et al. 2025 EULAR recommendations for the management of polymyalgia rheumatica and primary large vessel vasculitis. Ann Rheum Dis 2026 (online 21 July 2026; abstract). doi:10.1016/j.ard.2026.06.009
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Educational reference only — not a substitute for clinical judgment, institutional protocols, or specialist advice. Calculations run in your browser; nothing you enter is sent or stored.