Cardiolipin Antibodies | β2-Glycoprotein I Antibodies

Cardiolipin Antibodies

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Performance characteristics
EliA APS (pdf)
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Antigens

Cardiolipin is not, like most other autoantigens, a protein, but a phospholipid. Phospholipids are major components of membranes of living cells and of organelles within these cells. Cardiolipin is located in bacterial membranes, mitochondria, and chloroplasts.

Cardiolipin is made up of two phosphatidic acid groups, each attached to a glyceride moiety by a phosphodiester bond, and joined by a central glycerol moiety.

Antibodies bind to the complex of cardiolipin and the cofactor ß2-GPI.

Phadia assays are coated with purified cardiolipin.

Antibody specificity and prevalence

• Antiphospholipid syndrome (APS) (one of two laboratory criteria for the diagnosis of APS)
• Stroke (7%), stroke in young patients (18%)
• Pregnancy loss*: 3 or more consecutive pregnancy losses (15%), in 2nd or 3rd trimester (30%), with growth retardation and late loss (40%)
• Secondary APS in SLE (10-15%)
• Connective tissue diseases like SLE (44%), RA (4-49%), Scleroderma (25%), juvenile chronic arthritis (42%) (numbers of secondary APS included)
• Infectious diseases like Lyme disease (32%), syphilis (75%), leprosy (67%), tuberculosis (53%) and some more (Q fever, AIDS)
• Epilepsy (11%)
• Healthy individuals (0-7.5%)

* numbers refer to antiphospholipid antibodies in general

Information about the Antiphospholipid Syndrome

Disease activity

High aCL levels are associated with increasing risk for thrombosis or fetal loss. Raised anticardiolipin antibody levels may be detected many years prior to the expression of thrombosis or fetal loss. The risk for fetal loss increases from 6.5% (aCL negative) to 15.8% with aCL positivity.

When is the measurement recommended?

• Suspicion of antiphospholipid syndrome
• Fetal loss
• Stroke in young patients
• Unexplained thrombosis
• In discussion: migraine, epilepsy, chorea, heart valve disease, skin ulcers etc.

Antibody isotypes

IgG is accepted as the most frequent and most important isotype in aCL detection but the measurement of IgM and IgA is recommended, too, otherwise some risk patients would be lost. The clinical association of different aCL isotypes is discussed controversially in the literature.

References

• Moris V, Mackworth-Young C (1996) Autoantibodies to phospholipids. In: Van Venrooij WJ, Maine RN (eds.) Manual of biological markers of disease, Kluwer Academic Publishers, Dordrecht
• Khamashta MA, Hughes GRV (1996) Phospholipid Autoantibodies - Cardiolipin. In: Peter JB, Shoenfeld Y (eds.) Autoantibodies, pp 624-629, Elsevier, Amsterdam
• Roubey RA (1999) Immunology of the antiphospholipid syndrome: antibodies, antigens, and autoimmune response. Thromb Haemost 82: 656-661

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β2-Glycoprotein I Antibodies

Antigens

ß2-Glycoprotein I (ß2GPI) binds to negatively charged substances such as phospholipids and lipoproteins. An increasing number of studies indicate that ß2GPI is required as a cofactor or even is the "real" antigen for binding of antiphospholipid antibodies. The conformational epitopes for anti-ß2GPI develop when it interacts with a lipid membrane composed of negatively charged phospholipids or when ß2GPI is adsorbed on a polyoxygenated polystyrene plate.

ß2GP1 is a 50 kDa plasma protein, composed of five homologous motifs of approximately 60 amino acids.

ß2GP1 in Phadia assays is purified from human plasma.

Antibody specificity and prevalence

• Antiphospholipid syndrome (APS)
• Ischemic stroke (24%) 
• Pregnancy loss (7-14%) 
• Connective tissue diseases like SLE (36%), rheumatoid arthritis (RA), Scleroderma, juvenile chronic arthritis 
• Epilepsy (18%) 
• Healthy individuals (very rarely)

(available numbers vary widely because of different methods and isotypes)

Information about the Antiphospholipid Syndrome

Disease activity

High levels are associated with increasing risk for thrombosis or fetal loss.

When is the measurement recommended?

• Fetal loss 
• Stroke in young patients
• Unexplained thrombosis 
• in aCL negative patients with suspected APS 
• in aCL positive patients possibly having APS to confirm the diagnosis

Antibody isotypes

According to the Classification Criteria for Definite Antiphospholipid Syndrome (2006), IgG and IgM are the relevant isotypes for the detection of antibodies against beta 2 glycoprotein I. Nevertheless, an increasing number of studies indicate a clinical relevance of the isotype IgA, too. 

Detection methods

For antibody detection, ß2GP1 has to be bound to a lipid membrane composed of negatively charged phospholipids. Alternatively, ß2GP1 can be adsorbed onto a polyoxygenated (irradiated) polystyrene plate.

References

• Matsuura E, Koike T (1996) ß2-Glycoprotein 1 Autoantibodies. In: Peter JB, Shoenfeld Y (eds.), Autoantibodies, pp 109-114, Elsevier, Amsterdam
•  Reddel SW, Krilis SA (1999) Testing for and Clinical Significance of Anticardiolipin Antibodies. Clin Diagn Lab Immunol, Nov 99, 775-782 
• Tincani A, Balestieri G, Spatola L et al. (1998) Anticardiolipin and anti-ß2glycoprotein 1 immunoassays in the diagnosis of antiphospholipid syndrome. Clin Exp Rheumatol 16, 396-402

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