Anti-phospholipid syndrome

Clinical information

According to the classification criteria for anti-phospholipid syndrome (APS) of 1998 (also known as “Sapporo criteria”), APS can be diagnosed if at least one clinical and one serological criterion are met (Wilson et al., Arthritis Rheum (1999) 42:1309-1311). Clinical criteria include vascular thrombosis, which must be established according to the stipulated criteria, and pregnancy complications such as premature birth, spontaneous abortion and eclampsia. When the criteria were updated in 2004 (“Miyakis criteria”; Miyakis et al., J Thromb Haemost (2006) 4:295-306), antibodies against β2 glycoprotein 1 were added. Serological criteria now include the detection of antibodies against cardiolipin (ACA; IgG or IgM), against β2 glycoprotein 1 (anti-β2GP1; IgG or IgM) and a positive result in a type of coagulation test called lupus anticoagulant (LA) test. According to official recommendations, the serological criteria for APS diagnostics are only fulfilled when the result is confirmed 12 weeks later in a further test. The classification criteria were expanded in 2012 (Lakos et al., Arthritis Rheum (2012) 64:1-10) and now include the recommendation to also test for IgA if an IgG and IgM test for ACA or anti-β2GP1 is negative. The association of specific immunoglobulin classes with defined clinical parameters is controversially discussed.

Since around 10% of the healthy normal population exhibit anti-phospholipid antibodies (APLA) in the form of ACA or LA and these antibodies can also be induced by infections or certain medications (e.g. procainamide and hydralazine), a clinical criterion must be fulfilled in addition to a positive serological finding in order to diagnose APS.

Diagnostics

ELISA is the method of choice for detection of APLA, since it is highly sensitive, simple to perform and does not require fresh plasma. EUROIMMUN offers microtiter ELISAs for the quantitative determination of autoantibodies against cardiolipin, β2GP1 and phosphatidylserine of the individual immunoglobulin classes IgA, IgG or IgM or of several immunoglobulins (IgAGM) in one preparation. Alternatively, lupus anticoagulant can be determined using a multi-stage procedure as described in the guidelines of the International Society on Thrombosis and Haemostasis. The phospholipid-dependent coagulation tests used for this purpose have a high specificity for APS, but a low sensitivity. Moreover, since there is no gold standard, results vary depending on the test method used, making reliable serological diagnostics difficult.

EUROIMMUN ELISAs for the detection of antibodies against cardiolipin and β2GP1 show a very high specificity in clinical studies. Only 0% to 2% of sera from patients with viral hepatitis or parvovirus B19 infections and sera from healthy blood donors were positive, while values between 12% and 50% were obtained in studies using tests from other manufacturers. APLA can occur in cases of syphilis, which explains the somewhat high occurrence of ACA (11%) and anti-β2GP1 antibodies (13%) in these cases. The prevalence values of the two autoantibodies for APS (86%) and SLE (24% to 25%) obtained in a study using EUROIMMUN ELISAs correspond to data in literature. For ACA in particular a very high agreement with the results of an international meta-study was found (cohort of 1000 patients, 88% of APS patients were ACA positive Cervera R. et al., Arthritis Rheum (2002) 46:1019-1027).