Ales Ambrozic

European registry of babies born to mothers with antiphospholipid syndrome

Objectives This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the childs immunological profile with their mothers. Methods A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years. Results 134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β2 glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mothers antibodies before 6 months of age (p<0.05). Conclusion Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.

Laboratory criteria of the obstetrical antiphospholipid syndrome - Data from a multicentric prospective European women cohort

A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-beta2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS). We report new data on a prospective multicenter European cohort of 109 pregnant women having APS. Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-beta2-GPI IgM was present in three women. These results suggest that aCL and a-beta2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS. The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.

Obstetrical APS : Is there a place for hydroxychloroquine to improve the pregnancy outcome?

The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary.

Extended report: Development of patient-centred standards of care for osteoarthritis in Europe: the eumusc.net-project

Objective The eumusc.net project is an initiative founded by the European Community and the European League Against Rheumatism. One aim of the project was to facilitate equal standards for musculoskeletal health across Europe. The aim of this work-package was to develop patient-centred and consensus based standards of care (SOC) for osteoarthritis (OA), which should be available in a professional and a patient version. Methods A systematic review concerning guidelines dealing with OA was conducted. Furthermore, experts in musculoskeletal diseases were contacted to ensure that ‘grey’ literature was not excluded. Documents that fulfilled predefined inclusion/exclusion criteria were included and all interventions for OA were extracted and categorised. Based on this list of interventions, a three round Delphi exercise with an international and multidisciplinary expert panel, including patient research partners, was performed to achieve expert consensus. Results Six documents were included and used for further analysis. Out of them, 46 interventions have been extracted and 10 consensus based SOC were formulated. In addition, a patient version, written in a lay-understandable wording and in the format of checklist questions was developed. An example is SOC 5: “People with OA should achieve optimal pain control using pharmacological and non-pharmacological means.” The matching patient-centred checklist question reads: “Do I know how to control pain associated with OA?” Conclusions The SOC for OA will be available in the 23 languages of the European Union to enhance unified information to patients and professionals and to further harmonise the treatment/care of OA within Europe.

Heterogeneous behaviour of anti-beta2-glycoprotein I antibodies on different "high binding" microtiter plates.

We recently identified anti-β2GPI antibodies in a high proportion of sera from children with atopic dermatitis (AD) and showed that these anti- β2GPI most probably recognise domain V of β2GPI by contrast to anti-β2GPI from patients with the anti-phospholipid syndrome (APS) which epitopes apparently reside in domain I or IV. The aim of the present study was to compare the binding of IgG anti-β2GPI in AD and APS on four representative commerciallyavailable types of high binding microtiter plates. Selected plates: Costar, Nunc, Linbro and Sumilon C. Randomly selected sera from 29 children with AD and sera from 43 SLE patients (24 with secondary APS) were tested by anti-β2GPI ELISA using affinity purified β2GPI. Assays were calibrated with the HCAL, chimeric anti-β2GPI monoclonal antibodies with human γ1 constant regions. The calibration curves for HCAL were practically the same on all four types of plates. Sera from 7/24 APS patients with medium or high anti-β2GPI levels showed similar binding properties on all four plates, while 3/24 sera expressed values either slightly above or below the cut-off points. On the other hand, anti-β2GPI from AD sera showed very simmilar binding on Costar, Nunc and Linbro plates, while only 3/13 positive sera with the highest values on these 3 types of plates expressed low positive values for IgG anti-β2GPI on Sumilon C plates (Table ​(Table1).1). Except for one serum (low positive on Linbro plate) all sera from SLE patients without APS were negative on all the plates. Table 1 Our results point to substantial differences in the binding to β2GPI coated on different microtiter plates by anti-β2GPI in AD (with signs of APS) but not by anti-β2GPI in APS. In contrast to the other plate types, Sumilon C plates coated with β2GPI bound only minimally antibodies from AD children. If such anti-β2GPI prove non-thrombogenic, we will be able to increase the specificity of detecting anti-β2GPI relevant for APS by the use of this type of microtiter plates. Alternatively, if both anti-β2GPI specificities prove thrombogenic, we will be able to increase the sensitivity of the assay system by the use of other less discriminatory types of plates. k, slope of linear regression plot and R2 - determination coefficient: both compared to Costar. N, number of IgG anti-β2GPI positive sera in the group. *P < 0.001 (significant difference when compared with Costar, Nunc or Linbro)