AS01 ANTIPHOSPHOLIPID SYNDROME TOWARDS THE THIRD DECADE

001 - ANTIBODIES TO CARBAMYLATED Β2-GPI IN “SERONEGATIVE” ANTIPHOSPHOLIPID SYNDROME (ID 165)

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Abstract

Background and Aims

Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by recurrent thrombosis, pregnancy complications and circulating antiphospholipid antibodies (aPL). Anti-β2-Glycoprotein I (β2-GPI) are the main autoantibodies used for the diagnosis of APS. There are patients with APS negative for the “conventional” aPL tests (“seronegative APS”, SN-APS). Recently, several autoimmune responses have been described as a result of post-translational modifications of their target autoantigens. This study aims to evaluate carbamylated-β2-GPI (Carb-β2-GPI) as a new autoantigen of APS.

Methods

β2-GPI, carbamylated by potassium cyanate, was used to investigate its effect on monocyte-derived DC (moDC) phenotype and function. Sera from 114 SN-APS patients, 60 patients with APS, 20 with Rheumatoid Arthritis and 50 healthy donors were tested for anti-Carb-β2-GPI by ELISA.

Results

Our data indicate that Carb-β2-GPI is able to activate moDCs, inducing up-regulation of CD80, CD86, and CD40, activation of ERK, p38 MAPK and NF-kB and IL-12p70 release. Serological results showed that 37/114 SN-APS patients (32.45%) and 23/60 APS patients (38.33%) resulted positive for anti-Carb-β2-GPI. Interestingly, SN-APS patients tested positive for anti-Carb-β2-GPI showed a higher prevalence of thrombocytopenia (p=0.04, likelihood positive ratio of 3.9).

Conclusions

Data obtained from both functional tests on DCs and from immunologic approach suggest Carb-β2-GPI as a “new” antigenic target in APS. In particular, anti-Carb-β2-GPI showed potential utility in identification of a significant proportion of SN-APS patients. Furthermore, since patients tested positive for anti-Carb-β2-GPI reported a high risk of thrombocytopenia, this test may be proposed as an appropriate approach in the clinical evaluation of SN-APS.

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