False positive blood test results

Antibody in blood samples occurs by systemic connective tissue disorders og Vasculitis and can be useful when making a diagnosis. These samples are ordered at the laboratory based on clinical suspicion of the current disease. Unfortunately, the tests often show changes even though disease is not present (false positive results). The test results are often answered with results in titres. High titers are more susceptible to disease than low titers.

• A population study from northern Italy clearly showed elevated antinuclear antibody (ANA in titer 1: 160) in 8,2% of women and 3,7% of men. Most of these are unlikely to be ill or become ill (reference: Selmi C, 2016)
• The result of the antibody samples must therefore be interpreted with caution, especially at low values

Hepatitis, Rheumatic Disease and Antibody

• Please follow the link here

Some Autoimmune diseases and associated antibodies

Antifosfolipid Syndrome (ApLs)

Antibodies are detected at least twice at least 3 months apart to exclude random, transient results (false positives). Results in high titers and IgG antibodies are most important. People who have rash in all three types (lupus anticoagulant + cardiolipin + betaXUMUM glycoprotein) clearly have the highest risk of blood clots and spontaneous abortions.

• Lupus anticoagulant

  • Main marker for thromboembolism (blood clot) and risk of miscarriage. Analyzes at the coagulation laboratory

• Cardiolipin antibody

• Beta-2-Glycoprotein Antibody

Antisynthetase syndrome

• Jo-1 (Histidyl Antibody): common antibody at Antisynthetase syndrome (Lung Affection + Myositis + Antibody. Often Skin: Gottron's papules / signs, mechanic fingers, shawl / V signs, arthritis, Raynaud's phenomenon.)
• PL-7 (Theronyl antibody): Antisynthetase syndrome 
• PL-12 (Alanyl Antibody): Antisynthetase syndrome
• EJ (Glyceryl antibody): Antisynthetase syndrome 
• OJ (Isoleucyl antibody): Antisynthetase syndrome 
• KS (Asparaginyl Antibody): Antisynthetase syndrome 
• Ha-YRS (Tyrosyl antiBody): Antisynthetase syndrome 
• Zo (Phenylalanyl antibody) Antisynthetase syndrome
• SSA antibody (as by Sjögren's syndrome og SLE) also occurs at (dermato) myositis og Antisynthetase syndrome

MCTD (mixed connective tissue disease)

• ANA (antinuclear antibody)
• ENA (extractable antinuclear antibody)
• RNP (U1 small nuclear ribonucleoprotein particle (U1 snRNP)) which is mandatory part of the classification criteria and therefore with 100% occurrence (reference: Gunnarsson R, 2016)

Myositis and dermatomyositis

Literature: Betteridge ZE, 2011

Myositis Specific Antibody: (Immunological Laboratory OUS by appointment):

• SRP (Signal recognition particle (SRP) antibody): Myositis. Often acute onset of swallowing (esophageal insufficiency) and not all respond well to treatment (see also IMNM (immuno-mediated necrotizing myopathy) (reference: Kao HA, 2004)
• Mi-2 (Anti-Nucleosome Remodeling Deacetylal complex (NuRD)): Adult and juvenile (in children) dermatomyositis (JDM). Occurs at 4-18% with myositis (total) and 31% with Dermatomyositis (reference: Ghiradello A, 2004)
• P-155 / 140 / TIF1-γ: (Anti-Transcriptional Intermediary Factor 1 Gamma). Associated with Juvenile dermatomyositis and myopathy with severe skin affections in adults. Increased incidence of cancer in adults (Ref Muro Y, 2012). Juvenil DM with calcines
• SAE (anti-small ubiquitin-like modifier activating enzyme). Adults with dermatomyositis
• MDA-5 / Anti-CADM-140: (anti-Melanoma differentiation-associated genes 5). MDA-5 Syndrome, Amyopathic dermatomyositis, often with severe lung depression
• TIF1Υ / P-155 / 140 cancer associated myopathy / dermatomyositis
• NXP-2 (anti-nuclear matrix protein): cancer associated myopathy / dermatomyositis (Ref: Fierotino DF, 2013)
• HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase): Statin (cholesterol lowering drug) triggered myopathy (but may be available without statin use, then associated with high CK). Also associated with IMNM (Immunmediated Necrotizing Myopathy). Slightly increased cancer risk indicates general examination
• Jo-1 (histidyl antibody): common antibody at Antisynthetase syndrome (Lung Affection + Myositis + Antibody. Often Skin: Gottron's papules / signs, mechanic fingers, shawl / V signs, arthritis, Raynaud's phenomenon.)
• PL-7 (Theronyl antibody) Antisynthetase syndrome
• PL-12 (Alanyl antibody):  Antisynthetase syndrome
• EJ (Glyceryl antibody): Antisynthetase syndrome
• OJ (Isoleucyl antibody):  Antisynthetase syndrome 
• KS (Asparaginyl Antibody):Antisynthetase syndrome 
• Ha-YRS (Tyrosyl antiBody): Antisynthetase syndrome 
• Zo (Phenylalanyl antibody) Antisynthetase syndrome 
• SSA antibody (as by Sjögren's syndrome og SLE) also occurs at (dermato) myositis og antisyntetasesyndromet
• 5-NT1A (anti-cytosolic 5′-nucleotidase 1A) may be present at Inclusion Body-myositis (reference: Pick H, 2013)
• anti-Ku: Unspecific antibody that also occurs in several other autoimmune diseases such as RA, Systemic sclerosis, myositis and overlap syndromes (reference: Hi S, 2016)

Rheumatoid arthritis (RA), arthritis

• RF (Rheumatoid factors): Non-specific test that can be “false positive” in 13% of healthy people (Reference: Steiner R, 2002). Occurs at 60-80% at Rheumatoid arthritis (RA) (Reference: Steiner R, 2002). By joint symptoms can the test indicate arthritis (Rheumatoid arthritis (RA)
• Further medical investigation with anti-citrulline protein antibody (ACPA / CCP antibody) and further clinical assessment is necessary
  • CCP / ACPA: detected in 67% with Rheumatoid arthritis (RA), but rarely among healthy people (high specificity 95%) (Reference: Nishimura K, 2007)
  • CCP antibody may occur several years before the disease (RA) occurs
• ANCA (p-ANCA and atypical ANCA subgroups) may be positive at RA, but are without diagnostic significance

SLE (Systemic Lupus Erythematosus)

• Anti-nuclear antibody (ANA): Non-specific test that can be “positive” in healthy people (low titers in 18,1%, high titers in 6,1%, reference: Selmi C, 2015). If current symptoms are present, further investigations for connective tissue disease (see below), other autoimmune diseases (thyroiditis, hepatitis, Primary biliary cirrhosis), infection or cancer
  • ENA (extractable nuclear antibody): "Positive" test result strengthens suspicion of systemic connective tissue disease or other autoimmune condition, but does not provide assistance in further specification of diagnosis. However, the laboratory analyzes further with more specific tests (see below)
• DNA-Antibodies: Systemic Lupus (SLE). Low titers are also seen in healthy and some viral infections (HIV, Parvovirus B19, BK virus), as well as at autoimmune hepatitis (Liver inflammation). High titers are suspicious of SLE. Increased risk of renal infection (glomerulonephritis / lupus-free). The titers may vary somewhat with the disease activity
• Sm / SmD antibody: SLE (especially suspected if several other typical antibodies are also present). Increased incidence of cerebral lupus and renal failure. Low titers also appear among fresh
• C1q antibody is detected in up to 50% with SLE. Studies indicate an increased incidence of kidney disease and that the titles follow the disease activity (reference: Bock M, 2015)
  • C1q is also detected at
    • RA
    • Felty's syndrome
    • Hypochondrial urticaria (HUVS) (HUVS also occurs at SLE)
  • Reference range <10 U / ml
    • C1q (not anti-C1q) is often reduced by SLE (ref area 50-150 mg / L)
• PCNA antibody (proliferating cell nuclear antigen) is elevated in 5-10% with SLE (and primarily in Sjøgren's syndrome, as well as hepatitis B and C) (reference: Cozzani F, 2014). Is the discovery associated with various cancers (both solid tumors and haematological types) (reference: Guttroy A, 2016)
• SSA / Ro antibodies:
  • Sjögren's syndrome
  • SLE (30%), often subacute cutaneous type which rarely attacks internal organs, but causes rashes, especially during sunbathing
  • Myositis
  • Risk (1-2%) for the heartblock of the fetus in pregnancy (and neonatal lupus)
  • Ro60kD almost always at Sjøgren's syndrome, Ro52 kD is less specific
• SSB / la antibody: Sjøgrens syndrome (most often together with SSA), SLE (10%)
• RNP antibody: MCTD (mixed connective tissue disease) (100%), SLE (20-30%), Systemic sclerosis, myositis
• Lupus anticoagulant, anti-cardiolipin and anti-Beta2 glycoprotein are associated with Antifosfolipid syndrome which causes blood clots and spontaneous abortion. Also associated with neuropsychiatric SLE.
  • Use of anticoagulants (Marevan, Albyl-E, Factor Xa inhibitor (Xarelto, Eliquis) or Factor IIa inhibitor (Pradaxa)) affects the outcome
• Ribosomal P antibody relatively specific and associated SLE, particularly neuropsychiatric (cerebral) SLE. Detected among 13-40% with SLE (reference: Cozzani F, 2014)
• Histon antibody: "Positive" in relatively many healthy people, but may indicate drug-induced SLE
• NMO-IgG antibody (against aquaporin 4 water channel) is relatively specific to neuromyelitis optica and can help separate the condition from multiple sclerosis
• ANCA (p-ANCA and atypical ANCA) may be positive but are without diagnostic significance. However, the high-impact subgroups PR-3 and MPO-ANCA are suspected of respectively GPA (Wegener's granulomatosis) og MPA (microscopic polyangiite)

Sjögren's syndrome

• ANA (antinuclear antibody)
• ENA (extractable antinuclear antibody)
• SSA (Ro 52 and Ro60) (Sjøgren Syndrome A Antibody). SSA occurs at 76% (Reference: Palm O, 2013), but are among the less specific antibodies and also occur in others Autoimmune diseases that Myositis, thyroiditis (metabolic disease) and in many healthy people (especially in low titers)
• SSB (La) (Sjøgrens syndrome -B antibody) is seen at 40%, usually with SSA (Reference: Palm O, 2013)
• PCNA antibody (proliferating cell nuclear antigen) in primarily Sjøgrens syndrome (and in SLE). Has been found to be associated with various cancers (both solid tumors and hematological types) (Reference: Guttroy A, 2016)
• Autoimmune Metabolism Disorders (TPO antibody) and Primary biliary cirrhosis (liver disease) (mitochondrial antibody) may occur with Sjøgrens disease at 7-14% and 12%, respectively (reference: Patel R, 2014)

Systemic sclerosis (scleroderma)

• ANA (antinuclear antibody)
• ENA (extractable antinuclear antibody)
  • CENP (anti-centromere): Systemic sclerosis, limited form (especially suspected if at the simultaneously Raynaud's phenomenon )
  • Fibrillarin antibody
    • Please see U2-RNP below
  • Ku antibody: Nonspecific antibody that also occurs in several other autoimmune diseases such as RA, Systemic Sclerosis and Myositis: 1 of 3 has overlap syndrome (often with systemic sclerosis), 28% SLE, 4% dermatomyositis / polymyositis (DM / PM), 14 % Systemic Sclerosis and 20% Other Autoimmune Diseases (reference: HoT, 2003)
  • PM-Scl 100 or PM-Scl 75 indicates scleroderma myositis (myositis overlap: check skin changes, muscle strength, atrophies and CK, EMG and MRI thigh muscles, Raynaud's phenomenon). PM-Scl 100 or PM-Scl 75 occurs in approx. 80% with scleromyositis
  • RNA polymerase III: increased risk of renal crisis (new crisis with severe blood pressure increase and kidney failure)
  • SCL 70 (anti-topoisomerase I): Systemic sclerosis, diffuse type (especially if simultaneously Raynaud's phenomenon)
  • Th / Two Antibody: Occurs by Systemic Sclerosis, limited form. Supposedly increased risk of pulmonary manifestations og Pulmonary hypertension
  • U3-RNP (fibrillarine antibody). Most often by diffuse form of systemic sclerosis, but can also be seen by Primary Raynaud's phenomenon and SLE. Increased risk of Pulmonary arterial hypertension
  • NOR 90. Detected in less than 5% with systemic sclerosis. Appears in isolation and is associated with a mild course of disease. Not specific and can be seen in other systemic connective tissue disorders

 MAS / HLH

• Soluble IL-2 receptor  (sCD25) is a marker for lymphocyte activation and can be obtained from the Immunological lab Oslo University Hospital. Soluble IL-2 receptor is included in diagnostic criteria macrophage activation syndrome High values ​​are expected, but are not specific
  • Increased level of soluble IL-2 receptor also in other inflammatory diseases
    • RA, SLE, Sarcoidosis, psoriasis), infections and cancer (especially Lymphoma)

Vasculitis diseases

• anti-cytoplasmic antibody (ANCA): Non-specific test that is "positive" for various diseases (among others Ulcerative colitis og Crohn's disease) and sometimes in healthy people.
  • PR3- ANCA: GPA / Wegeners granulomatosis og EGPA / Churg Strauss vasculitis: Further investigated
  • MPO-ANCA: Microscopic Polyangiitis (MPA): Further investigations (renal failure?)

• anti-C1q: Hypochondrial urticaria vasculitis (HUV))
  • The antigen is Complement factor C1q

Encephalitis (brain inflammation)

• GKC complex, mostly LGi1 (face and arm cramps)
• anti-hu (cranial neuropathy)
• anti-GBA-b receptor (cramps)
• anti-GAD65 (Stiff-person Syndrome, New Diabetes I)
• AMPAR antibody (psychosis)
• anti-NMDAR (psychosis, cramps)
• D2R (dystonia)
• GlyR (hyperplexia, overreaction)
• GABA -AR (convulsions)
• Caspr2 (muscle cramps, facials)
• DPPX (myoclonus, delirium, superficial intestine)
• Ma2 (cranial neuropathy)
• Miller-Fisher (cranial neuropathy), (cranial neuropathy)

(Reference: Lancaster E, 2016)

Antibody occurs in serum and in spinal fluid.

Other conditions & antibody:

• Addison's disease: 21 hydroxylase
• alopecia areata: T cells
• Anti-glomerular basement membrane (GBM) syndrome: Please see Goodpasture's syndrome below
• Antisynthetase syndrome: see above
• Celiac Disease: Anti-tissue transglutaminase, anti-GM-1, anti-GD1a, anti GQ1b
• Demyelinating polynevropathy chronic inflammatory : anti-ganglioside antibody, anti MAG
• Diabetes mellitus type 1: anti-glutamate decarboxylase (GADA), ocular cell antibody (ICA), insulinoma-associated antibody (IA-2), anti-insulin antibody
• Encephalitis
  • anti-NMDA receptor encephalitis
  • Anto-MGO encephalomyelitis
  • GAD65 antibody is also detected at Autoimmune epilepsy, including Limbic encephalitis which may be related to cancer, especially cancer tested (see also limbic encephalitis below). PNMA2 in limbic encephalitis
  • Cerebral stem encephalitis
    • PNMA2
• Goodpastures syndrome: Anti-Glomerolus Basement Membrane (Anti-GBM).
  • The antigen is the alpha3 chain of type IV collagen
  • About. 35% also has ANCA antibody, most often MPO-ANCA as in vasculitis (Microscopic polyangiite, MPA)
• Graves Disease (Hyperthyroidism) Tyreotropin antibody (TRAS)
• Guillian-Barre syndrome: anti-ganglioside
• Hashimotos encephalopathy: anti-alpha endolase
• Hashimotos thyroiditis: anti-thyroid peroxidase (TPO) and / or thyroglobin
• Hepatitis (Autoimmune): anti-smooth muscle (SMA), LKM-1 (Liver-Kidney Microsomes), anti-F actin (3-10% of healthy)
• Hyperthyroidism, Please see Grave's disease above
• Hypothyroidism, please see Hashimoto's thyroidite above
• Labert-Eaton myasthenic syndrome: Voltage-gated calcium channel antibody, Q-type calcium channel, synaptogagmin, muscarinic acetylcholine receptor M1, SOX1. NOTE! Small cell lung carcinoma
• Lembic encephalitis: VGKC antibody, GAD65, PNMA2, CV2. (See also encephalitis above)
• Hepatitis (autoimmune, “lupiod”): anti-LKM-1, LKM-2, or LKM-3, anti soluble liver antigen (anti-SLA, anti-LP)
• BUT: See soluble IL-2 receptor above
• MCTD: see above
• Miller-Fisher Syndrome / Guillian Barre: anti GQ1b
• Morvan's syndrome: VGKC antibody
• Multiple Sclerosis (MS): anti-Kir4.1
• Myastenia gravis: anti-Nicotinic acetylcholine receptor, MuSK protein. anti-Titin (NOTE! Thymoma in Myasthenia)
• Myositis: see above
• Narcolepsy: anti-hypocretin or orexin
• Neuromyelitis optics (Devic's Disease): NMO-IgG Aquaporin 4
  • Aquaporin -negative cases may be related to MOG antibody (see encephalitis above)
• Pancreatitis (autoimmune): anti-lactoferrin, anti-carbonic anhydrase
• Paraneoplastic cerebellar degeneration: Anti-Yo (anti-cdr-2 in purkinje fibers), anti-Hu, anti-Tr, antiglutamate receptor
• Pemfigus vulgaris: Anti-Skin Desmosome IIF (Desmoglein 3)
• Pemphigus bullous type: Anti-Skin Basement Membrane IIF
• Pernicious anemia: anti-parietal cell
• Polyendocrine syndrome (autoimmune)
  • Triad (often from childhood): chronic candiasis, hypoparathyroidism, adrenal insufficiency.
  • Anti-INF-ω or anti INF-α
  • Genetic diagnosis: sequencing of the AIRE gene
• Primary biliary cirrhosis: anti-p62, anti-sp100, anti-Mitochondria (M2), anti SSA / Ro
• Rasmussen's encephalitis (chronic focal encephalitis): anti-NR2A
• Rheumatic fever: Streptococcal M protein cross-reacts with human myosin
• Rheumatoid arthritis: See above
• Sarcoidosis: ACE (Angiotensin Converting Encyme), Soluble IL-2 Receptor
• Schmidts syndrome (autoimmune polyendocrine syndrome type2): anti-21 hydroxylase, anti-17 hydroxylase
• SLE: See above
• Stiff person syndrome: Glutamate acid decarboxylase (GAD). Amphiphysin. Amphiphysin-1 is associated with breast cancer.
• Systemic sclerosis: see above
• Thrombocytopenic purple (autoimmune): anti-gpIII1 or 1b-IX. See also thrombocytopenia below.
• Thrombocytopenia: glycoprotein IIb-III3 or Ib-IX by ITP, anti-ADAMTS13 in TTP and HOUSE, anti-cardiolipin and beta2 glycoprotein in antifosfolipid syndrome (and lupus anticoagulant) and anti HPA-1a, anti-HPA-5b and others at NAIT
• Thyroiditis (Autoimmune): Please see Hashimoto's Thyroiditis above
• Vasculitis diseases: see above
• Urticaria vasculitis: anti-C1q antibody, soluble IL-2 receptor

Literature

Monarch PA, 2014 (vasculitis antibody)

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