Welcome to the Autoimmunity 2021 Congress Calendar

Background and Aims

It is well established that the humoral immunity in antiphospholipid syndrome (APS) is presented by circulating pathogenic anti-β2GPI autoantibodies. These antibodies play a major role in the disease pathogenesis by targeting mainly domain I of the β2GPI protein. In the current trial, we had orally administered a domain-I derivative of the β2GPI molecule, in order to evaluate a new therapeutic approach: induction of oral tolerance in a mouse model of APS.

Methods

BALB/c mice immunized with β2GPI, were fed with either domain-I, domain-V or complete β2GPI molecule.

Results

β2GPI immunized mice developed experimental APS which were fed with domain-I significantly had decreased fetal loss (p<0.004), a lower size of thrombi (p<0.001) and lower circulating anti-β2GPI Abs in comparison to mice fed with domain-V or PBS (p<0.002). Likewise, Domain-I
fed mice had a lowered inflammatory response, exhibited by decreased expression of inflammatory cytokines (IFNγ, IL-6, IL-17) and elevated production of IL-10 anti-inflammatory cytokine by splenocytes. Moreover, the anti-inflammatory response in the domain-I fed APS mice was associated with alterations in circulating miRNAs, which is associated with immunomodulation of the immune network.

Conclusions

Our results show that DI-β2GPI fed APS mice developed tolerance scenario manifested by a reduction in fetal loss, thrombi size, inhibition of inflammatory cytokine production and upregulation of IL-10 and T regulatory cells. This sequence of events is associated with circulating plasma miRNA related to the immune network. Therefore we propose the DI-β2GPI derivative treatment for patients with APS.

Background and Aims

Circulating immunecom­plexes between IgA anti Beta2-glycoprotein (aB2GP1) antibodies and B2GP1 (B2A-CIC) have been associated with acute thrombotic events in patients positive for IgA aB2GP1. In renal transplantation, B2A-CIC associates early graft loss. Interestingly, patients negative for B2A-CIC and positive por IgA aBGP1 have the same risk than those without antiphospholipid antibodies. The aim of this study is to determine the role of B2A-CIC after heart trasplantation.

Methods

151 consecutive patients who received a heart transplant were followed-up for 2 years. IgA aB2GP1 and B2A-CIC were quantified in pretransplant serum samples. Patients were divided into 3 groups: Group-1, positive for IgA aB2GP1 and B2A-CIC (N=19). Group-2, only positive for IgA aB2GP1 (N=28). Group-0 (control group): IgA aB2GP1 negative (N=104).

Results

Mortality in Group-1 was higher than group-0 at 3 months (HR:5.08; 95%CI: 1.36-19.01). There were no significant differences between group-2 and group-0. Multivariate analysis identified B2A-CIC as the most important independent risk factor for early mortality (OR=6.12; 95% CI:1.93-19.4).

Post-transplant incidence of thrombosis was higher in Group-1 than control group (OR:6.42; 95%CI: 2.1-19.63). Multivariate analysis identified B2A-CIC (OR:6.13; 95%CI:2.1-19.63) and pretrasplant active smoking as independent risk factor for thrombosis.

The proportion of patients who had thrombotic events or died in the first trimester was significantly higher in group-1 (73.7%) than in group-0 (16.3%; p<0.001) and in group-2 (39.3%; p=0.02). Multivariate analysis identified B2A-CIC as the main independent risk factor for early outcomes (mortality or thrombosis) in the first three months after heart transplant (OR=11.42, 95% CI: 1.69-9.68).

Conclusions

B2A-CIC predict early mortality and thrombosis after heart transplant

Background and Aims

Preeclampsia complicates about 10-17% of pregnancies with antiphospholipid syndrome (APS). It is often severe and might occur sometimes at early gestation. The development of preeclampsia before fetal viability is a huge challenge for obstetricians and demands an intensive discussion regarding the therapeutical options.

.

Methods

We retrospectively reviewed the data of 7 women with primary APS who developed preeclampsia before 24 weeks of gestation.

Results

Plasma exchange had been performed in four of the cases and two women received corticosteroids. One of the women had received 20 mg of pravastatin daily, starting at 18 weeks of gestation. Neonatal outcome was: live birth in four cases and IUFD in three cases. The main pediatric complications were noted in a 28-week-old premature born boy, who developed severe IRDS and thrombocytopenia. At the present time, the boy continues to have a retarded status.

Conclusions

This retrospective analysis revealed that women with APS can develop severe preeclampsia even before 20 weeks of gestation. Several management options for prolongation of pregnancy such as plasma exchange, pravastatin, LMHW, hydroxychloroquine/HCQ, or TNF-alpha blocker should be discussed with the patients.

Optimal management of preeclampsia before 24 weeks of gestation usually depends on weighing the maternal and fetal complications from expectant management with prolongation of pregnancy versus the predominant fetal and neonatal risks of extreme prematurity from “aggressive” management with immediate delivery.

Background and Aims

The relevance of antiphospholipid (aPL), antibodies in women undergoing in vitro fertilization (IVF) is debated. There are several studies regarding this topic but to date none of them evaluated the specific role of aPL antibodies in the context of IVF with donor oocytes.

The aim of this study is to investigate the prevalence and clinical association of aPL antibodies on women undergoing first oocyte donation fertility treatment.

Methods

Eighty consecutive women who underwent IVF with donor oocytes were prospectivelly studied in a fertility centre. Plasma levels of classical (anticardiolipin antibody IgG/IgM, anti-β2-glycoprotein I IgG/IgM) and non-classical (anti-β2-glycoprotein I IgA, aPS/PT IgG/IgM and anti-anexine V IgG/IgM) antiphospholipid antibodies were measured by ELISA method. IVF and pregnancy outcomes were assessed.

Results

In the studied cohort 13,75% (11/80) were positive or in grey zone for aPL antibodies, 6,25% (5/80) were positive for non-classical aPL antibodies and only 7.5% (6/80) for classic aPL antibodies. IVF and pregnancy outcomes was described for aPLs positive patient compared to aPL negative population. Although live birth rate was similar in both groups, misscarriage rate in APL+ was 35% compared to 16% in APL- population. Pregnancy complications ocurred in 14% of APL+ vs 2% in APL- group.

Conclusions

Despite the low prevalence of this or aPL antibodies in this cohort, the presence of non-conventional aPL antibodies was associated with adverse IVF and pregnancy outcomes.The testing of non-conventional aPL antibodies might be useful to identify a group of patients that could benefit of specific treatment.

Background and Aims

Antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP) are important factors in diagnosis of celiac disease (CD). This study aimed to compare the performance of novel tTG and DGP assays with reference methods using clinically characterized samples.

Methods

A total of 461 samples were included in the study, consisting of 161 samples from CD patients, and 290 samples from patients with various other diseases including other gastroenterological conditions. All samples were tested by a novel fully automated particle-based multi-analyte technology (PMAT, research use only, Inova Diagnostics, USA). Additionally, all samples were tested in parallel using chemiluminescent based assays currently on the market (QUANTA Flash, Inova Diagnostics, USA). Qualitative correlations were calculated, and clinical performance was assessed for each of the analytes.

Results

The results derived from the clinical evaluation and the method comparisons are summarized in the tables below.

Conclusions

Our data show good agreement between the results obtained using the novel PMAT assays and the reference methods. Additionally, all analytes in the Aptiva Celiac Disease IgA and IgG Reagents showed excellent clinical performance.

Background and Aims

Behçet’s disease (BD) is a systemic autoinflammatory disorder characterized by recurrent oral ulcers, genital ulcers, ophthalmologic, musculoskeletal, vascular and cutaneous manifestations. Vascular involvement in BD is present in up to 40% of cases, 75% of which are venous, whereas the other 25% are arterial.

Methods

Herein, we present a 36-year-old male with previous medical history of psoriasis, and deep vein thrombosis (DVT) of the right common iliac vein following a pyeloplasty. Then, a year later, with ongoing anti-vitamin K treatment, he made a new DVT of the right popliteal and distal femoral veins, so anticoagulation was switched to enoxaparin for 1.5 months, and later switched to dabigatran. One year later, with a new episode of left popliteal DVT, it was decided to keep anticoagulation with enoxaparin.

Results

In association, he presented a migratory tibio-tarsal arthritis, oral aphthosis and erythema nodosum, which led us to the diagnosis of BD. Immunosuppressive therapy was started with corticosteroid and methotrexate (regarding his past history of psoriasis), without further episodes of thrombosis until then.

Conclusions

While the role of immunosuppressive therapy is well acknowledged, a controversy exists regarding the value of anticoagulant treatment, and the usefulness of anticoagulation in different vascular manifestations related to BS is still unclear. However, the presence of DVT in atypical sites other than the lower extremities, should raise concern over new episodes of DVT in the future. Therefore, anticoagulation should be considered in these patients associated with immunosupressive therapy, which is the key for a successful therapy.