Autoimmune Disease Workup Pathway

From the clinical picture to directed serology, classification criteria and the next tests · v3.0

Antibody Atlas

What each antibody points to, what it is worth, and what it obliges you to do next. The action column is the part that matters: an antibody that does not change management is a laboratory result, not a clinical finding.

1. Nuclear Antibodies of Lupus and Overlap

Antibody	Points to	Diagnostic worth	Action it obliges
Anti-dsDNA	SLE, lupus nephritis	6 points in the 2019 criteria, but only on an assay with documented 90 per cent or better specificity. An ELISA or CLIA qualifies when the laboratory documents that performance; one of unknown specificity does not.	Monitor serially. A rising titre with falling C3 and C4 precedes a nephritis flare.
Anti-Sm	SLE, essentially only SLE	The most specific antibody in the panel. Specificity 99.7 per cent, likelihood ratio around 65, but sensitivity only 17 per cent.	Establishes the diagnosis. Do not repeat it: it does not track activity.
Anti-nucleosome	SLE	Similar specificity to anti-Sm with more than twice the sensitivity, around 42 per cent. Under-used in Indian laboratories.	Worth requesting when SLE is suspected and dsDNA and Sm are negative.
Anti-ribosomal P	Neuropsychiatric SLE, lupus hepatitis	Specificity around 99.6 per cent, sensitivity around 32 per cent.	In a patient with psychosis, supports a lupus attribution. It does not remove the obligation to exclude CNS infection first.
Anti-histone	Drug-induced lupus, but also idiopathic SLE	Sensitive, not specific. Useless without the drug history.	Take a full drug history including isoniazid, hydralazine, phenytoin, minocycline and anti-TNF agents.
Anti-U1 RNP	MCTD at high titre, SLE at any titre	High titre with no SLE-specific antibody suggests MCTD, but clinical features are still required.	Baseline echocardiography. Pulmonary arterial hypertension is the leading cause of death in MCTD.
Anti-DFS70	Argues against a rheumatic disease	Only when monospecific, that is with no other antibody detectable. Present in a few per cent of healthy people.	In an otherwise well person with a dense fine speckled ANA, this is the result that lets you stop.

2. Ro, La and the Pregnancy Consequence

Antibody	Points to	Diagnostic worth	Action it obliges
Anti-Ro60 (SSA)	Sjögren's, SLE, subacute cutaneous lupus	3 of the 4 points needed to classify Sjögren's. Cannot classify alone.	In a woman planning or carrying a pregnancy, this is the finding that changes obstetric care.
Anti-Ro52 (TRIM21)	Myositis, antisynthetase syndrome, interstitial lung disease, autoimmune hepatitis	Frequently misreported as a Sjögren's marker. It is not one in isolation.	Where the phenotype includes lung disease, treat as a signal to screen the lungs.
Anti-La (SSB)	Sjögren's, when accompanying anti-Ro	Absent from the 2016 criteria. An isolated anti-La carries little weight.	Do not diagnose Sjögren's on an isolated anti-La.

Anti-Ro and pregnancy. Maternal anti-Ro antibodies cross the placenta and can cause neonatal lupus and congenital complete heart block. The risk of heart block in a first pregnancy is of the order of 1 to 2 per cent, rising substantially after a previously affected child. Serial foetal echocardiography through the second trimester is the standard response. This applies to any anti-Ro positive woman, whether or not she has been given a rheumatological diagnosis.

3. Sclerosis Antibodies and What Each Predicts

Antibody	Phenotype	Principal organ risk	Action it obliges
Anti-topoisomerase I (Scl-70)	Diffuse cutaneous systemic sclerosis	Interstitial lung disease	Baseline HRCT thorax and pulmonary function tests, then serial monitoring.
Anticentromere	Limited cutaneous disease, the CREST phenotype	Pulmonary arterial hypertension, late	Annual echocardiography. Lung fibrosis is less likely.
Anti-RNA polymerase III	Rapidly progressive diffuse skin thickening	Scleroderma renal crisis; also an association with malignancy around disease onset	Daily home blood pressure monitoring, and age-appropriate cancer screening.
Anti-PM-Scl	Sclerosis and myositis overlap	Lung and muscle	Assess both compartments.
Anti-fibrillarin (U3 RNP)	Diffuse disease, often younger patients	Pulmonary hypertension, cardiac and renal	Echocardiography and cardiac assessment.
Anti-Th/To	Limited disease	Interstitial lung disease and pulmonary hypertension	Do not be reassured by limited skin involvement. Screen the lungs.

Corticosteroids in systemic sclerosis. Doses above about 15 mg of prednisolone daily are associated with precipitating scleroderma renal crisis, and the risk is greatest in early diffuse disease and in anti-RNA polymerase III positive patients. Where steroids cannot be avoided, use the lowest effective dose and monitor blood pressure and renal function closely.

4. Myositis-specific Antibodies: One Antibody, One Syndrome

Antibody	Syndrome	What it predicts	Action it obliges
Anti-Jo-1 and other antisynthetases	Antisynthetase syndrome: myositis, ILD, arthritis, mechanic's hands, Raynaud's, fever	Interstitial lung disease dominates the prognosis, and can precede the muscle disease	HRCT thorax and pulmonary function tests at diagnosis, whatever the CK.
Anti-MDA5	Clinically amyopathic dermatomyositis with rapidly progressive ILD; cutaneous ulceration and palmar papules	Rapidly progressive, frequently fatal interstitial lung disease. CK is often normal or near normal, which is the point that catches people out	Urgent HRCT thorax. Early aggressive combined immunosuppression. Treat as a respiratory emergency, not a dermatological finding.
Anti-TIF1-gamma	Adult dermatomyositis with prominent skin disease	The strongest malignancy association among the myositis antibodies in adults. In juvenile disease it carries no malignancy association	Age-appropriate and symptom-directed malignancy screening at diagnosis, and repeated over the following three years.
Anti-NXP2	Dermatomyositis with calcinosis	Calcinosis, severe muscle disease; malignancy association in adults	Malignancy screening in adults. Anticipate calcinosis in juvenile disease.
Anti-Mi-2	Classic dermatomyositis with the full rash	Good response to treatment, favourable prognosis, low malignancy risk	Reassure, and treat conventionally.
Anti-SAE	Dermatomyositis, skin often precedes muscle	Dysphagia is common	Assess swallowing.
Anti-SRP	Immune-mediated necrotising myopathy	Very high CK, severe weakness, poor response to corticosteroids alone; cardiac involvement described	Early escalation beyond steroids: intravenous immunoglobulin or rituximab.
Anti-HMGCR	Immune-mediated necrotising myopathy, statin-associated	Weakness that persists or progresses after the statin is stopped. Can also occur without any statin exposure	Stop the statin, but do not expect that to be enough. Immunosuppression, often with intravenous immunoglobulin, is usually required.
Anti-Ku	Myositis and sclerosis overlap	Variable, often overlap features	Assess for both.

5. ANCA and Anti-GBM

Result	Points to	Cautions	Action it obliges
PR3-ANCA	Granulomatosis with polyangiitis	Also positive in cocaine adulterated with levamisole, which produces a strikingly similar destructive nasal picture	Ask about cocaine use before accepting the diagnosis. Exclude tuberculosis before accepting a cavitating lung lesion as GPA.
MPO-ANCA	Microscopic polyangiitis, EGPA, drug-induced vasculitis	The least specific result in the panel. Also seen in inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, endocarditis and tuberculosis, and with propylthiouracil, hydralazine and minocycline	A positive MPO-ANCA without a vasculitic syndrome is not a diagnosis and is not an indication to treat.
Immunofluorescence pattern alone	Nothing definite	The 2017 international consensus moved to antigen-specific immunoassay for PR3 and MPO as the primary screen. A c-ANCA or p-ANCA report without antigen specificity is an incomplete result	Request the antigen-specific assay before acting.
Anti-GBM	Anti-glomerular basement membrane disease	Around a third are also ANCA positive, usually MPO. Double-positive disease behaves like anti-GBM acutely and like ANCA vasculitis in its tendency to relapse	A true emergency. Plasma exchange, corticosteroids and cyclophosphamide, without waiting for biopsy where the presentation is fulminant. Test for ANCA in every anti-GBM patient.

6. Antiphospholipid Antibodies

Assay	Note	Action it obliges
Lupus anticoagulant	The strongest single predictor of thrombosis of the three. Cannot be interpreted reliably on warfarin, a direct oral anticoagulant, or during acute thrombosis	Time the test. If the patient is anticoagulated, say so on the request form and interpret with the laboratory.
Anticardiolipin IgG or IgM	Only medium or high titre counts: above 40 GPL or MPL units, or above the 99th centile	A low-titre transient positive after infection is common and should not be classified.
Anti-beta-2 glycoprotein I	Above the 99th centile	Part of the triple-positive assessment.
Triple positivity	All three positive carries the highest thrombotic risk	Warfarin, not a direct oral anticoagulant. The TRAPS trial found rivaroxaban inferior to warfarin in triple-positive patients, with excess arterial events.

The 12-week rule. Antiphospholipid antibodies must be persistently positive on two or more occasions at least 12 weeks apart before the syndrome can be classified. Transient positivity after infection is frequent. Committing a patient to lifelong anticoagulation on a single positive result is the commonest serious error in this area.

7. What a Negative Panel Does Not Exclude

A module organised around antibodies can imply, by its silence, that a negative panel is reassuring. It is not. The following are substantially or entirely seronegative, and several are more common in Indian practice than the diseases above.

Disease	How it is diagnosed instead
Takayasu arteritis	Imaging of the aorta and its branches: CT or MR angiography. Young Indian women with limb claudication, absent pulses, a blood pressure difference between arms, or unexplained hypertension. No serological marker.
Behçet's disease	Clinical: recurrent oral and genital ulceration, uveitis, pathergy. HLA-B51 supports but does not diagnose.
Axial spondyloarthritis	Inflammatory back pain, sacroiliac imaging, HLA-B27. ANA and RF are irrelevant.
Adult-onset Still's disease	Quotidian fever, evanescent rash, arthritis, very high ferritin with a low glycosylated fraction. Diagnosis of exclusion. ANA and RF negative by definition in the classification criteria.
Sarcoidosis	Histology showing non-caseating granulomas, after tuberculosis has been excluded. In India that exclusion is the whole difficulty.
IgG4-related disease	Histology with storiform fibrosis and IgG4-positive plasma cells. Serum IgG4 is neither sensitive nor specific enough to stand alone.
Polymyalgia rheumatica and giant cell arteritis	Clinical, with acute phase response, temporal artery imaging or biopsy.
ANA-negative SLE	A small but real group. The 2019 criteria cannot classify them, and the authors say so explicitly. Classification criteria are not diagnostic criteria.

8. Organ-specific Antibodies: When to Send, and What Confirms

Signposts only. None of these is scored by the module, and in each the antibody supports a diagnosis that something else anchors.

Picture	Antibody	What anchors the diagnosis	Source
Nephrotic syndrome, bland sediment	Anti-PLA2R	With nephrotic syndrome, a positive anti-PLA2R makes a biopsy unnecessary to confirm membranous nephropathy. Associated conditions are looked for whatever the result.	KDIGO 2021, practice points 3.1.1 and 3.1.2
Blistering or erosive skin and mucosal disease	Anti-desmoglein 1 and 3; anti-BP180 and BP230	Perilesional biopsy with direct immunofluorescence. In bullous pemphigoid the ELISA supports; clinical picture, histology and immunofluorescence make the diagnosis.	Borradori 2022 (pemphigoid)
Acute flaccid weakness; ophthalmoplegia with ataxia	Anti-ganglioside; anti-GQ1b	Clinical diagnosis, nerve conduction and CSF. The antibodies have limited value and a negative result does not exclude GBS; anti-GQ1b is found in up to 90 per cent of Miller Fisher syndrome.	Leonhard 2019
Subacute encephalopathy with seizures, focal signs or CSF pleocytosis	Neuronal antibodies, serum and CSF	Clinical criteria for possible autoimmune encephalitis, with alternatives excluded. Treatment is not held for the antibody, which can take weeks.	Graus 2016
Raised ALT, hepatitic pattern	ANA, anti-smooth muscle, anti-LKM1, anti-SLA	IgG elevation, autoantibodies and compatible histology, taken together.	EASL 2025
Raised ALP, cholestatic pattern	AMA-M2; sp100 and gp210 when AMA is negative	In an adult with cholestasis and no likelihood of systemic disease, raised ALP with AMA is diagnostic.	EASL 2017

1. Why Pre-test Probability Is the Whole Argument

The probability that the patient has the disease before the result is known. It decides what a positive result means, and nothing about the assay changes it.

In the United States NHANES survey, antinuclear antibodies were present in 13.8 per cent of the population aged 12 and over. Take a clinic where 1,000 people are tested and 20 of them have lupus. At a sensitivity of 98 per cent and a specificity of 90 per cent, about 20 of the 20 with lupus test positive and about 98 of the 980 without it also test positive. Of 118 positive results, 20 are true. A positive ANA in that setting is wrong about five times out of six.

Who is positive without being ill. The 13.8 per cent is at a 1:80 cut-off and is not spread evenly. In NHANES it was 17.8 per cent of women against 9.6 per cent of men, and it rose with age, with the female-to-male ratio peaking at 40 to 49 years (Satoh 2012). The same titre in a 60-year-old woman and in a 20-year-old man is not the same finding.
The question to ask before ordering. Not "could this be lupus" but "what would I do differently if it came back positive, and what would I do differently if it came back negative". If the answer to both is nothing, the test is not indicated.
Indian context. ANA is increasingly ordered from primary care and in direct-to-consumer laboratory packages, bundled into a panel the patient bought with no clinical question attached, and unpicking an incidental low-titre ANA in a well person now takes up a great deal of rheumatology outpatient time. Stage 1 of this module exists to make the prior explicit before the number is looked at.

2. What Each Dilution Means

Fifteen international reference laboratories tested sera from healthy individuals on HEp-2 cells at four dilutions (Tan EM, Feltkamp TE, Smolen JS, et al. Arthritis Rheum. 1997;40(9):1601-1611). The figures below are the proportion of healthy people positive at each, and they are the reason a titre is reported at all.

Titre	Healthy people positive	What it means at the bedside
1:40	31.7 per cent	Almost a third of well people. Sensitive, and close to useless on its own. Below the entry criterion for the 2019 SLE criteria, which this module therefore will not apply at 1:40.
1:80	13.3 per cent	The 2019 SLE entry criterion, and the NHANES cut-off. Roughly one well person in eight. Entry to the criteria, not evidence of disease.
1:160	5.0 per cent	Excludes about 95 per cent of well people. Tan and colleagues recommend laboratories report at both 1:40 and 1:160 for exactly this reason.
1:320 and above	3.3 per cent at 1:320	Uncommon in health, and where the likelihood ratio starts to do real work. Still not a diagnosis: 3.3 per cent of a large well population is a large number of people.

Titre and pattern are two different results. The titre says how much antibody is present. The pattern says what it is against. A high titre with no pattern reported and no clinical syndrome is a laboratory number; a moderate titre with a centromere pattern in a woman with Raynaud's is a diagnosis waiting to be confirmed.

3. The Great Indian Mimics

Before an autoimmune diagnosis is accepted in India, the endemic mimics must be actively excluded, not merely considered. Empirical corticosteroids given to a patient with disseminated tuberculosis are not a neutral act.

The mimic	How it presents	Which antibodies it can turn positive	What separates them
Tuberculosis	Chronic fever, weight loss, cavitating lung lesions resembling GPA, serositis, Poncet's reactive polyarthritis	RF, low-titre ANA, occasionally ANCA	Tissue diagnosis, CBNAAT, culture. A cavitating lesion in India is tuberculosis until proven otherwise.
Leprosy	Polyarthritis, neuropathy, skin lesions. Type 2 lepra reaction with erythema nodosum leprosum closely mimics systemic vasculitis	ANA, RF, sometimes ANCA, and false-positive antiphospholipid antibodies	Slit skin smear, nerve thickening, the distribution of the skin lesions.
Dengue and chikungunya	Severe symmetric polyarthritis, rash, thrombocytopenia. Chikungunya arthritis can persist for months and is regularly mistaken for early rheumatoid arthritis	RF, low-titre ANA, transient antiphospholipid antibodies	The epidemic context, the acute febrile prodrome, and serology for the virus.
Kikuchi-Fujimoto disease	Young woman, fever, tender cervical lymphadenopathy, cytopenias. Reproduces an SLE flare closely, and can coexist with SLE	Low-titre ANA	Lymph node biopsy. There is no serological shortcut.
HIV	Cytopenias, arthralgia, sicca, vasculitic rash, diffuse infiltrative lymphocytosis syndrome resembling Sjögren's	ANA, RF, antiphospholipid antibodies	HIV testing before immunosuppression, without exception.
Hepatitis C	Cryoglobulinaemic vasculitis, arthralgia, sicca	RF strongly positive, ANA, antiphospholipid antibodies	Hepatitis C serology and viral load. It is also a formal exclusion in the Sjögren's criteria.
Infective endocarditis	Fever, glomerulonephritis, splinter haemorrhages, low complement, cytopenias. Reproduces lupus nephritis and ANCA vasculitis together	ANCA, RF, ANA, low C3 and C4	Blood cultures before antibiotics, and echocardiography. This is the classic error: a patient given pulse steroids for a presumed pulmonary-renal syndrome who had endocarditis.
IgG4-related disease	Tumefactive masses, pancreatitis, sialadenitis, retroperitoneal fibrosis. Mimics Sjögren's and vasculitis	Modestly raised serum IgG4; ANA can be positive	Histology showing storiform fibrosis and an IgG4-positive plasma cell infiltrate.

4. Static and Dynamic Markers

Repeating a static marker costs money, delays nothing and answers no question. Where the patient is paying out of pocket, a repeated ENA panel is a real harm.

Static: establish the diagnosis, do not repeat

ANA by immunofluorescence, and its pattern
Anti-Sm, anti-Ro, anti-La
Anti-U1 RNP, anti-Scl-70, anticentromere
Myositis-specific antibodies
Anti-CCP

Titres do not track disease activity. Once positive, the information has been obtained.

Dynamic: monitor serially

Anti-dsDNA titre
Complement C3 and C4
Urine protein-creatinine ratio and sediment
ANCA titre, in selected patients
Creatine kinase, in myositis

A rising anti-dsDNA with falling C3 and C4 precedes a lupus nephritis flare and is the pairing worth watching.

5. The ANA Pattern Is Half the Test

The staining pattern on HEp-2 cells, standardised internationally as ICAP anti-cell (AC) codes, predicts which antibodies will be found. A titre reported without a pattern has discarded half of what the test produced.

Pattern	ICAP code	Expect	Associations
Homogeneous	AC-1	dsDNA, nucleosome, histone	SLE, drug-induced lupus, juvenile idiopathic arthritis
Dense fine speckled	AC-2	DFS70, and nothing else	Argues against a rheumatic disease when monospecific
Centromere	AC-3	CENP-A, CENP-B	Limited cutaneous systemic sclerosis, primary biliary cholangitis
Fine or coarse speckled	AC-4, AC-5	Ro, La, Sm, U1 RNP	SLE, Sjögren's, MCTD
Nuclear dots	AC-6, AC-7	Sp100, PML	Primary biliary cholangitis
Nucleolar	AC-8 to AC-10	Scl-70, PM-Scl, fibrillarin, Th/To, RNA pol I	Systemic sclerosis and overlap
Nuclear envelope	AC-11, AC-12	gp210, lamins	Primary biliary cholangitis, autoimmune hepatitis
Cytoplasmic	AC-15 to AC-21	Jo-1, ribosomal P, AMA-M2, SRP	Myositis, neuropsychiatric SLE, primary biliary cholangitis

Point to note. A cytoplasmic pattern is frequently reported by laboratories as "ANA negative", because strictly it is not nuclear. In a patient with myositis or unexplained interstitial lung disease that reported negative may be concealing an anti-Jo-1. Read the comment on the report, not only the conclusion.

6. Classification Criteria Are Not Diagnostic Criteria

They exist to assemble homogeneous groups for research, and are weighted towards specificity so that trial cohorts are clean.

The authors of the 2019 SLE criteria state directly that the criteria "should never be used to exclude patients who do not fully meet these criteria from receiving appropriate therapies".
The commonest misuse is the reverse of the one people expect: not that criteria are used too loosely, but that a patient who genuinely has the disease is denied treatment because a score came to 8 rather than 10.
This module reports the score and says whether the threshold is met. It does not tell you whether to treat.

7. Likelihood Ratios, and Why This Module Refuses to Multiply Them

Post-test odds equal pre-test odds multiplied by the likelihood ratio, but sequential multiplication is only valid when the tests are conditionally independent given the disease state. Autoantibodies are not: a patient with anti-Sm is far more likely than chance to also have anti-dsDNA and a high-titre ANA, and multiplying the ratios treats correlated evidence as independent.

This module applies the single strongest likelihood ratio present, names it, and states its source and its limitations on screen.
The one composite figure it uses, the likelihood ratio attached to the number of positive autoantibodies, was measured as a composite in the source study and is legitimate as a single step.
Provenance. The likelihood ratios come from Li and colleagues, a retrospective study of 1,297 patients at a single Chinese tertiary hospital, of whom 148 had SLE. The comparison group is other patients who had the panel sent, not healthy people, so these figures describe a rheumatology referral population. Li graded the ANA as immunofluorescence intensity, 1+ to 4+, not as a dilution titre; the titre bands this module uses are an approximate alignment, which is one more reason to read the output as an order of magnitude. They should not be applied to unselected screening, and no equivalent Indian dataset was available. Where the module shows a probability it repeats this caveat.

8. What This Module Does Not Cover

Stated so that the boundary is explicit rather than implied.

Organ-specific autoimmunity is signposted, not classified. Autoimmune hepatitis, primary biliary cholangitis, membranous nephropathy, pemphigus and pemphigoid, Guillain-Barré syndrome and autoimmune encephalitis each get a signpost to the test that confirms them (Antibody Patterns, section 8). Coeliac disease, autoimmune thyroid disease, type 1 diabetes and LADA, myasthenia gravis, AQP4 and MOG antibody disease, and autoimmune gastritis are not covered.
The seronegative diseases are signposted, not classified. Their criteria are named with their entry rules, but none is scored.
The EULAR/ACR 2017 myositis probability is not computed. Those criteria convert a weighted score into a probability through a published regression model whose coefficients could not be verified to the standard this project requires. The module interprets the myositis-specific antibodies instead, and says so on every run.
The ACR/EULAR 2023 antiphospholipid criteria are not applied. Sydney 2006 is what the module applies, and those criteria are verified against the primary record. The 2023 criteria exist and are more restrictive.
Paediatric practice is not covered. The weights and thresholds here are the adult ones.
Disease activity indices are not calculated. SLEDAI, BVAS, mRSS and the ESSDAI are separate instruments.

Abbreviations

AC code (ICAP Anti-Cell code) · ACPA (Anti-Citrullinated Protein Antibody) · ACR (American College of Rheumatology) · AMA-M2 (Anti-Mitochondrial Antibody, M2 Subtype) · AOSD (Adult-Onset Still Disease) · ANA (Antinuclear Antibody) · ANCA (Antineutrophil Cytoplasmic Antibody) · APS (Antiphospholipid Syndrome) · AQP4 (Aquaporin-4) · ASAS (Assessment of SpondyloArthritis international Society) · ATT (Anti-Tubercular Therapy) · BP180 / BP230 (Bullous Pemphigoid Antigens 180 and 230 kDa) · BVAS (Birmingham Vasculitis Activity Score) · C3 (Complement Component 3) · C4 (Complement Component 4) · c-ANCA (Cytoplasmic Antineutrophil Cytoplasmic Antibody) · CBNAAT (Cartridge-Based Nucleic Acid Amplification Test) · CCP (Cyclic Citrullinated Peptide) · CD4 (Cluster of Differentiation 4) · CENP-A / CENP-B (Centromere Protein A / Centromere Protein B) · CK (Creatine Kinase) · CLIA (Chemiluminescence Immunoassay) · CNS (Central Nervous System) · CRP (C-Reactive Protein) · CSF (Cerebrospinal Fluid) · CT (Computed Tomography) · DFS70 (Dense Fine Speckled 70 kDa) · DIF (Direct Immunofluorescence) · DLCO (Diffusing Capacity of the Lung for Carbon Monoxide) · DMARD (Disease-Modifying Antirheumatic Drug) · dsDNA (Double-stranded DNA) · EADV (European Academy of Dermatology and Venereology) · EASL (European Association for the Study of the Liver) · EEG (Electroencephalogram) · EGPA (Eosinophilic Granulomatosis with Polyangiitis) · ELISA (Enzyme-Linked Immunosorbent Assay) · ENA (Extractable Nuclear Antigen) · ENT (Ear, Nose and Throat) · ESR (Erythrocyte Sedimentation Rate) · ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index) · EULAR (European Alliance of Associations for Rheumatology) · GBM (Glomerular Basement Membrane) · GBS (Guillain-Barré Syndrome) · GCA (Giant Cell Arteritis) · gp210 (Glycoprotein 210 kDa) · GPA (Granulomatosis with Polyangiitis) · HEp-2 (Human Epithelial Type 2 Cell Line) · HIV (Human Immunodeficiency Virus) · HLA (Human Leucocyte Antigen) · HMGCR (3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase) · HRCT (High Resolution Computed Tomography) · HSV (Herpes Simplex Virus) · ICAP (International Consensus on ANA Patterns) · ICBD (International Criteria for Behçet's Disease) · IFA (Immunofluorescence Assay) · IGRA (Interferon-Gamma Release Assay) · IgG (Immunoglobulin G) · IgG4 (Immunoglobulin G4) · IgM (Immunoglobulin M) · IIM (Idiopathic Inflammatory Myopathy) · ILD (Interstitial Lung Disease) · ISN/RPS (International Society of Nephrology / Renal Pathology Society) · ISTH (International Society on Thrombosis and Haemostasis) · Jo-1 (Histidyl-tRNA Synthetase) · KDIGO (Kidney Disease: Improving Global Outcomes) · LADA (Latent Autoimmune Diabetes in Adults) · LDH (Lactate Dehydrogenase) · LFT (Liver Function Tests) · LKM1 (Liver-Kidney Microsomal Antibody Type 1) · LR (Likelihood Ratio) · MCP (Metacarpophalangeal) · MCTD (Mixed Connective Tissue Disease) · MDA5 (Melanoma Differentiation-Associated Gene 5) · MOG (Myelin Oligodendrocyte Glycoprotein) · MPA (Microscopic Polyangiitis) · MPO (Myeloperoxidase) · MR (Magnetic Resonance) · MRI (Magnetic Resonance Imaging) · mRSS (Modified Rodnan Skin Score) · MSA (Myositis-Specific Antibody) · NHANES (National Health and Nutrition Examination Survey) · NXP2 (Nuclear Matrix Protein 2) · OSS (Ocular Staining Score) · PAH (Pulmonary Arterial Hypertension) · p-ANCA (Perinuclear Antineutrophil Cytoplasmic Antibody) · PIP (Proximal Interphalangeal) · PLA2R (Phospholipase A2 Receptor) · PL-12 (Alanyl-tRNA Synthetase) · PL-7 (Threonyl-tRNA Synthetase) · PML (Promyelocytic Leukaemia Protein) · PM-Scl (Polymyositis-Scleroderma) · PMR (Polymyalgia Rheumatica) · PR3 (Proteinase 3) · RA (Rheumatoid Arthritis) · RF (Rheumatoid Factor) · RNA (Ribonucleic Acid) · RNP (Ribonucleoprotein) · SAE (Small Ubiquitin-like Modifier Activating Enzyme) · SLA (Soluble Liver Antigen) · Scl-70 (Scleroderma 70 kDa Antigen, Topoisomerase I) · SLE (Systemic Lupus Erythematosus) · SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) · SpA (Spondyloarthritis) · Sp100 (Speckled 100 kDa Protein) · SRP (Signal Recognition Particle) · SSA (Sjögren's Syndrome-Related Antigen A) · SSB (Sjögren's Syndrome-Related Antigen B) · SSc (Systemic Sclerosis) · TIF1-gamma (Transcriptional Intermediary Factor 1 Gamma) · TNF (Tumour Necrosis Factor) · TRIM21 (Tripartite Motif-containing Protein 21) · TSH (Thyroid Stimulating Hormone) · UACR (Urine Albumin-to-Creatinine Ratio) · UPCR (Urine Protein-to-Creatinine Ratio)

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How to Cite This Tool

DOIhttps://doi.org/10.5281/zenodo.22401558

AMA Style:Umakanth S. Autoimmune Disease Workup Pathway. Version 3.0. MEDiscuss Clinical Decision Support System. Published 2026. Accessed . https://mediscuss.org/cdss/autoimmune-profile-evaluator. doi:10.5281/zenodo.22401558

Vancouver Style:Umakanth S. Autoimmune Disease Workup Pathway [Internet]. Version 3.0. MEDiscuss.org; 2026 [cited ]. Available from: https://mediscuss.org/cdss/autoimmune-profile-evaluator. doi:10.5281/zenodo.22401558

Category Advanced DiagnosticsPathway

Specialties Immunology, Internal Medicine, Rheumatology, Nephrology

Status Essential

Written and maintained by

Dr Shashikiran Umakanth

Last revised 24 September 2026

How these tools are written and reviewed

Autoimmune Disease Workup Pathway

Stage 1. Clinical Context and Pre-test Probability

Stage 2. The Antinuclear Antibody

Stage 3. Directed Antibody Panel

Stage 4. Confirmatory and Organ-staging Tests

Antibody Atlas

1. Nuclear Antibodies of Lupus and Overlap

2. Ro, La and the Pregnancy Consequence

3. Sclerosis Antibodies and What Each Predicts

4. Myositis-specific Antibodies: One Antibody, One Syndrome

5. ANCA and Anti-GBM

6. Antiphospholipid Antibodies

7. What a Negative Panel Does Not Exclude

8. Organ-specific Antibodies: When to Send, and What Confirms

1. Why Pre-test Probability Is the Whole Argument

2. What Each Dilution Means

3. The Great Indian Mimics

4. Static and Dynamic Markers

5. The ANA Pattern Is Half the Test

6. Classification Criteria Are Not Diagnostic Criteria

7. Likelihood Ratios, and Why This Module Refuses to Multiply Them

8. What This Module Does Not Cover

Save this calculation

Autoimmune Disease Workup Pathway

How to use this tool

What this tool does not cover

Stage 1. Clinical Context and Pre-test Probability

Stage 2. The Antinuclear Antibody

Stage 3. Directed Antibody Panel

Stage 4. Confirmatory and Organ-staging Tests

Antibody Atlas

1. Nuclear Antibodies of Lupus and Overlap

2. Ro, La and the Pregnancy Consequence

3. Sclerosis Antibodies and What Each Predicts

4. Myositis-specific Antibodies: One Antibody, One Syndrome

5. ANCA and Anti-GBM

6. Antiphospholipid Antibodies

7. What a Negative Panel Does Not Exclude

8. Organ-specific Antibodies: When to Send, and What Confirms

1. Why Pre-test Probability Is the Whole Argument

2. What Each Dilution Means

3. The Great Indian Mimics

4. Static and Dynamic Markers

5. The ANA Pattern Is Half the Test

6. Classification Criteria Are Not Diagnostic Criteria

7. Likelihood Ratios, and Why This Module Refuses to Multiply Them

8. What This Module Does Not Cover

Save this calculation