Background: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of venous and/or arterial thrombosis, habitual miscarriage (HM), thrombocytopenia, and various neurological, skin, cardiovascular and haematological disorders, in the presence of aPLs, namely antiphospholipid antibodies (aPL) [2, 4]. Antibodies against β2-glycoprotein I (anti-β2GPI antibodies) and cardiolipin (aCL), together with the functional assay lupus anticoagulant (LAC), are the three laboratory tests considered in the revised criteria for the diagnosis of the syndrome .
Although aPL are found in 1% to 5% of the general population, the prevalence of APS is said to be no more than 0.5%. APS may be associated with other autoimmune diseases, mainly SLE, but it can also be found in patients having neither clinical nor laboratory evidence of another definable condition (primary APS). Occasionally it can accompany other diseases, such as infections, drugs or malignancies .
In 30-35% of systemic lupus erythematosus (SLE) cases, aPL are associated with the development of secondary antiphospholipid syndrome, which is on the background of unfavourable prognosis for SLE. Hp (haptoglobin) is a hemoglobin-binding glycoprotein of α2-globulin serum proteins fraction induced by seromucoid proteins at the early stages of an inflammatory process. The main practical value of Hp phenotype test in SLE patients is to predict a genetic predisposition to the development of APS to provide optimal management.
Objectives: Determine the carriage frequency of different Hp phenotypes in SLE patients with APS, and reveal a correlation between the level of serum Hp and clinical manifestations.
Methods: The study is based on the follow-up results of 103 SLE patients at the Republican Centre of Rheumatology in Tashkent Medical Academy. Entry criteria: reliable diagnosis of SLE, verified with SLICC (2012) criteria. The diagnosis of secondary APS (SAPS) was based on the Sydney (2006) Classification Criteria for APS. Hp test was performed using disc polyacrylamide gel electrophoresis (PAGE).
Results: We has defined APS in 44 of 103 (42.7%) SLE patients. In 29 of 44 (65%) cases the APS diagnosis was based on major manifestations, and in 15 of 44 (35%) – by the presence of two or more additional signs. Distribution of SLE patients with APS, depending on the Hp phenotype: 38 (86.4%) patients with APS had Hp 1-1, 6 (13.6%) – Hp 2-1, 0 (0%) - Hp 2-2 (P<0.01, 95% CI). Distribution of SLE patients without APS depending on the Hp: 23 (39%) patients – Hp 1-1, 27 (45.8%) – Hp 2-1, 9 (15.3%) – Hp 2-2. After distribution of the patients into groups according to the Hp value, more than 3 g/l (I group) and less than 3 g/l (II group), we have analysed the correlation between Hp and clinical manifestations of APS: thrombocytopenia: I – 7 (22,5%), II – 3 (23,07%), HM – I – 13 (41,9%), II – 4 (30,7%), livedo reticularis: I – 15 (48,3%), II – 5 (38,4%), finger gangrene: I – 5 (16,1%), II – 0 (0%); finger necrosis: I – 6 (19,3%), II – 1 (7,6%); migraine: I – 20 (64,5%), II – 5 (38,4%); chorea: I – 5 (16,1%), II – 2 (15,3%); transitory ischemic attack (TIA): I – 16 (51,6%), II – 7 (53,8%); chronic ulcers of lower extremities: I – 22 (70,9%), II – 8 (61,5%) (P<0.05, 95% CI).
Conclusions: Results of our investigation showed that development of SLE and APS is characteristic for Hp 1-1 phenotype. Apparently, it Hp 1-1 a predisposing factor to the development of autosensitisation and is a genetic marker for APS. The results related to clinical manifestations of APS, depending on the level of Hp showed expressed correlation between Hp level and clinical manifestations of APS.
- Abou-Nassar K, Carrier M, Ramsay T et al. The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis. Thromb Res 2011;128:77–85.
- Cervera R, Espinosa G. Update in the catastrophic antiphospholipid syndrome and the ‘CAPS Registry’. Semin Thromb Hemost 2012;38:333-8.
- Nayfe R, Uthman I, Aoun J, Saad Aldin E, Merashli M, Khamashta MA. Seronegative antiphospholipid syndrome. Rheumatology. 2013;52(8):1358–1367.
- Otomo K, Atsumi T, Amengual O, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum 2012;64:504-12.
- Sciascia S, Sanna G, Murru V, Khamashta MA, Bertolaccini ML. Validation of a commercially available kit to detect antiphosphatidylserine/prothrombin antibodies in a cohort of systemic lupus erythematosus patients. Thrombosis Research. 2014;133(3):451–454.