Antiphosphatidylethanolamine Antibodies Research Articles

Comparison of anti-phospholipid antibody titers before and after SARS-CoV-2 mRNA vaccination in hospital staff

Multiple concerning reports have emerged of cardiovascular complications, particularly thrombosis, following mRNA vaccination against the SARS-CoV-2 pathogen. The presence of serologically persistent anti-phospholipid antibodies is a characteristic of antiphospholipid syndrome, which presents with clinical manifestations including thrombosis or pregnancy morbidity. Anti-SARS-CoV-2 mRNA vaccines pose a theoretical risk of cross-reactivity between the SARS-CoV-2 spike protein and phospholipids in host tissues. In this study, serum anti-phospholipid antibody titers before and after SARS-CoV-2 mRNA vaccination were compared among 184 hospital staff members. Although no significant differences were found in terms of antibody titers targeting cardiolipin and β2-glycoprotein I, post-vaccination antibody titers targeting phosphatidylethanolamine were found to be significantly increased compared to pre-vaccination levels (p = 0.008). Anti-phosphatidylethanolamine antibodies are the most common anti-phospholipid antibodies detected in patients with recurrent miscarriages at < 10 weeks of gestation. However, the association between vaccination and these types of adverse events remains unknown, thus warranting further investigation.

Non-criteria antiphospholipid antibodies in antiphospholipid syndrome: Diagnostic value added.

Non-criteria antiphospholipid antibodies (aPLs) increase the diagnostic value for antiphospholipid syndrome (APS) and contribute to better recognition of seronegative APS (SNAPS). However, the clinical utility and the diagnostic value of non-criteria aPLs are inconsistent. This study aimed to investigate the prevalence and clinical significance of 7 non-criteria aPLs in a large APS cohort. Seven non-criteria aPLs, including anti-phosphatidylserine/prothrombin (aPS/PT) antibodies IgG/IgA/IgM, anti-phosphatidylethanolamine antibodies (aPE) IgG/IgA/IgM, anti-Annexin V antibodies (aAnnexinV) IgG/IgA/IgM, anti-phosphatidylserine antibodies (aPS) IgM, aPS IgG, antibodies directed againsta mixture of phospholipids(APhL) IgG, and APhL IgM were tested among 175 patients with APS, 122 patients with other autoimmune diseases (as disease controls), and 50 healthy controls. In the present study, the highest prevalence of non-criteria aPLs was seen in aAnnexinV (58.86%). APhL IgG and aPS IgM showed the highest specificity (95.35%) and aPS/PT showed the highest Youden index (0.3991) for the diagnostic value of APS. The aAnnexinV also showed the highest prevalence in SNAPS (43.3%), followed by APhL IgM (21.7%), aPE (16.7%) and aPS/PT (16.7%). APhL IgG, aPS/PT, and aPS IgG showed positive association with thrombotic events in APS patients [APhL IgG: odds ratio (OR) = 2.26, 95% confidence interval (CI) 1.18-4.34, p = 0.013; aPS/PT: OR = 2.48, 95% CI: 1.32-4.69, p = 0.004; aPS IgG: OR = 1.90, 95% CI 1.01-3.60, p = 0.046; respectively). The inclusion of the non-criteria aPLs increased the accuracy of APS diagnosis from 65.7% to 87.4%. Our data provide evidence that adding the non-criteria aPLs can improve the diagnostic accuracy in APS. APhL IgG, aPS/PT, and aPS IgG may be potential biomarkers to predict the risk of thrombosis in APS.

Levels and avidities of antiphosphatidylethanolamine antibodies in patients with thrombotic events and immunologically-mediated diseases.

Antiphosphatidylethanolamine antibodies (aPE) represent one type of antiphospholipid antibody (aPL) directed against the neutral phospholipids - phosphatidylethanolamines. The aim of this study was to evaluate levels and avidities of aPE in several groups of patients and compare them with conventional aPLs. aPE were analysed in a cohort consisting of 68 hospitalized patients. The other cohort comprised 22 patients with immunologically-mediated diseases. The control group consisted of 20 healthy persons. ELISA methods were used for determination of aPL. Avidities of aPE were tested by modified ELISA with urea as a chaotropic agent. aPE IgG/IgM were significantly higher in the group of patients with venous thromboembolism than those with non-thrombotic internal disorders (P=0.02 for both Ig classes). aPE IgG/IgM elevated above cut-off values were found in 10.8% of patients with venous thromboembolism and as a single aPL in 6.5%. Levels of aPE IgG higher than our limit (>6 U/mL) were detected in 29% of patients with immunologically-mediated diseases with other positive aPL. Low-, intermediate- and high-avidity aPE IgG were found in patients of both cohorts. The avidities of aPE IgG differed from those of anticardiolipin antibodies IgG. Neither aPE IgG levels nor avidity dynamics significantly changed during follow-up. aPE may be related to venous thromboembolism and may be part of the repertoire of aPL in immunologically-mediated diseases. There are patients with thrombosis negative for conventional aPL but positive for aPE. aPE IgG may have different avidities.

Significance of Anti-Phosphatidylethanolamine Antibodies in the Pathogenesis of Recurrent Pregnancy Loss.

Anti-phosphatidylethanolamine antibody (aPE), an anti-phospholipid autoantibody (aPL), has been proposed as a factor in recurrent pregnancy loss (RPL). However, conflicting views exist on the pathogenicity of RPL, and aPE has not yet been included in the classification criteria for antiphospholipid syndrome (APS). Here, we aimed to determine the clinical importance of examining aPE. aPE (IgG, IgM) was measured in 1705 patients with a history of RPL and re-examined after a 12-week interval in patients who tested positive. Persistent positive patients were administered low-dose aspirin during the subsequent pregnancy and clinical outcomes depending on the presence, type, and persistence of aPE were evaluated. Among the patients positive for aPE IgG and aPE IgM in the first examination (n= 117; 6.87%, and n= 235; 13.6%, respectively), 31.5% and 37.6% were negative upon re-examination, respectively. Moreover, among the cases with known pregnancy outcome, the miscarriage rate in the cumulative positive aPE group was 32.6% (29/89), which did not differ significantly from that of the aPE negative group (27.7%; 80/209; P= 0.178). Alternatively, the miscarriage rate in the persistently positive group was 40.7% (22/54), which was significantly higher than that in the transient positive group, 20.0% (7/35) (P= 0.041). Particularly, this difference become more significant when focusing on aPE IgM, 46.9% (15/32) in the persistent, compared with 16.7% (4/24) in the transient positive group (P= 0.024). aPE IgM is suggested to serve as a pathogenic aPL together with anti-cardiolipin antibodies and lupus anticoagulants, particularly if these factors persist over an extended period of time.

Increased Plasma Levels of Platelet Factor 4 and β-thromboglobulin in Women with Recurrent Pregnancy Loss.

Thrombosis in decidual vessels is one of the mechanisms of pregnancy loss. However, few studies have assessed the relation between platelet activation, which is known to cause of thrombosis, and recurrent pregnancy loss (RPL). We investigated platelet activation in women with RPL compared to controls by measuring plasma levels of platelet factor 4 (PF4) and β-thromboglobulin (βTG), and assessed correlations between PF4/βTG and coagulative risk factors associated with RPL. The study group included 135 women who had experienced two or more consecutive pregnancy losses. The control group included 28 age-matched healthy women who had never experienced pregnancy loss. PF4 and βTG plasma levels were significantly higher in the women with RPL than controls (PF4: 14.0 [8.0-20.0] vs. 9.0 [6.0-12.0] ng/ml, p=0.043; βTG: 42.0 [24.3-59.8] vs. 31.5 [26.6-36.4] ng/ml, p=0.002). There was a significant association between βTG and anti-phosphatidylethanolamine antibody immunoglobulin M (aPE IgM) (p=0.048). Among the women with RPL, 18 of those who were positive for PF4 (45%) and 18 of those who were positive for βTG (37%) were negative for all known coagulative risk factors associated with RPL. Measurements of PF4 and βTG may be important because they help identify women who are at risk of RPL.

Quelle place pour la recherche des anticorps antiphosphatidyléthanolamine dans la suspicion du syndrome des antiphospholipides séronégatif ?

PurposeAntiphospholipid syndrome (APS) is a clinico-biological syndrome, which associates vascular injury and persisting antiphospholipid antibodies (aPL). Patients with clinical symptoms of APS but without aPL are defined as “seronegative APS” (SNAPS). The aim of this study was to evaluate antiphosphatidylethanolamine antibody (aPE) investigation in patients with SNAPS suspicion. MethodsThis retrospective study was conducted in patients with SNAPS suspicion. A homemade enzyme-linked immunosorbent assay (ELISA) was used to search for aPE. The results of this homemade method were compared with those from a global screening ELISA. ResultsTwo hundred twenty-eight patients with SNAPS suspicion were included. Among them, 58.3% had a thrombotic event. The homemade ELISA found positive persisting aPE in 23 patients (10%): 15 with a thrombotic event, 6 with obstetrical morbidity and 2 with a combined event. The global screening ELISA was positive in only 11 of these 23 patients (47.8%). ConclusionThese results suggest the implication of aPE in SNAPS.

Thromboses in tuberculosis are linked to antiphosphatidylethanolamine antibodies levels: A cross-sectional study

Venous thromboses have been associated with tuberculosis, but the relationship with circulating anticoagulant has not been studied yet. In a cohort of 48 patients with tuberculosis, 22.9% of them presented with venous thromboses significantly associated with dose dependent level of antiphosphophatidyl-ethanolamine antibodies.

Antiphosphatidylethanolamine Antibodies and Deep Vein Thrombosis in Lupus Patients with Antiphospholipid Syndrome

Abstract Backgroud. Which factors determine venous thrombotic events in some antiphospholipid syndrome (APS) patients and arterial thrombosis or conditions related to pregnancy in others has not been established yet. Purpose. The aim of this study was to search the antiphospholipid antibodies (APLAs) correlates in regard to deep vein thrombosis (DVT) in patients with systemic lupus erythematosus (SLE) and APS. Methods. Twenty-nine patients fulfilling the criteria of both SLE and APS were included. Complete anamnesis and clinical examination was performed on inclusion. Also, for all patients, disease activity was assessed by the SLEDAI score. An extended APLAs profile, ten Abs, was searched. Results. The titers of IgG anticardiolipin (aCL), IgG anti-β2 glycoprotein I (aβ2GPI), IgG antiphosphatidylethanolamine (aPE), and also of IgG antiprothrombin (aPT) were significant higher in patients with DVT history. After analysis by ROC curve and univariate logistic regression, the strongest association was found for IgG aPE. Also, in multivariate analysis, SLEDAI score correlated with the DVT antecedents. Conclusions. IgG aPE might be involved in DVT pathogenic pathways in patients with SLE and APS as their titers remain significantly higher in patients with previous DVT. Lupus patients with DVT events represent a subgroup of patients with more severe underlying pathology.

Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies

Phosphatidylethanolamine (PE) is a major phospholipid species with important roles in membrane trafficking and reorganization. Accumulating clinical data indicate that the presence of circulating antibodies against PE is positively correlated with the symptoms of antiphospholipid syndromes (APS), including thrombosis and repeated pregnancy loss. However, PE is generally sequestered inside a normal resting cell, and the mechanism by which circulating anti-PE antibodies access cellular PE remains unknown. The studies presented here were conducted with synthetic PE-binding agents, plasma samples from patients with anti-PE autoimmunity, and purified anti-PE antibodies. The results suggest that the cellular vulnerability to anti-PE antibodies may be mediated by the binding of PE molecules in the membrane of the early endosome. Endosomal PE binding led to functional changes in endothelial cells, including declines in proliferation and increases in the production of reactive oxygen species, as well as the expression of inflammatory molecules. Collectively, our findings provide insight into the etiology of anti-PE autoimmunity and, because endosomes are of central importance in almost all types of cells, could have important implications for a wide range of biological processes.

Serum Interleukin-23 in Polish Patients with Systemic Lupus Erythematosus: Association with Lupus Nephritis, Obesity, and Peripheral Vascular Disease

Objectives To analyze the correlation between the serum concentration of interleukin- (IL-) 23 and atherosclerotic changes, traditional atherosclerotic risk factors, the autoantibody profile, and involvement of selected organs in systemic lupus erythematosus (SLE) patients. Patients and Methods We studied 94 SLE patients and 27 controls. We analyzed the IL-23 serum concentration, autoantibodies, carotid intima-media thickness and atherosclerotic plaque, the ankle-brachial index, atherosclerotic risk factors, and organ manifestations. Results Concentrations of IL-23 significantly differed between SLE patients and the controls (p = 0.0015). On the basis of multivariate stepwise analysis, we revealed that high levels of IL-23 were associated with atherosclerotic plaque in common femoral arteries (OR = 12.67; 95% CI: 1.41–113.84), lupus nephritis (OR = 3.69; 95% CI: 1.16–12.22), and obesity (OR = 4.21; 95% CI: 1.40–12.67). Autoantibodies related to IL-23 were anti-phosphatidylethanolamine antibodies (OR = 11.06; 95% CI: 1.24–98.65) and anti-SS-B/La antibodies (OR = 15.43; 95% CI: 1.73–137.25). Conclusions IL-23 may be involved in lupus nephritis pathogenesis. Through its association with obesity and selected antiphospholipid antibodies, IL-23 might promote a hypercoagulable state contributing to atherothrombosis development in SLE patients.

The outcome of ELISA for antiphosphatidylethanolamine antibodies is dependent on the composition of phosphatidylethanolamine

ObjectiveThe presence of circulating autoantibodies against phosphatidylethanolamine (PE) has been shown to be positively associated with symptoms of antiphospholipid syndromes (APS). However, the current ELISA-based tests for antiphosphatidylethanolamine (aPE) antibodies remain inconsistent and controversial. The term PE refers to a collection of phospholipids that have phosphorylethanolamine head group as a common structural feature, but can vary in fatty acids with diverse physicochemical properties. The present study was to investigate, using synthetic positionally symmetrical PE species as a model system, the impact of PE structural variations on aPE ELISA. MethodsSingle and combinations of synthetic PE species, including 16:0 (fatty acid length:degree of unsaturation), 18:0, 18:1, 20:4 and 22:6, were screened with ELISA using serum samples from aPE patients and compared with chicken egg PE. There were a total of 37 aPE patient serum samples, including 11 cofactor-independent IgM, 14 ABP-independent IgG and 12 ABP-dependent aPE serum samples (3 IgM, 8 IgG and 1 IgA). The ELISA conditions were investigated for different isotypes and cofactor dependence. Based on the initial screening, adjustments in phospholipid compositions were made for achieving optimal OD readings. Finally, we isolated total IgG from aPE sera to validate different antigenic preferences. ResultsThe antigenic preference was different among immunoglobulin isotypes and between cofactor-dependent versus cofactor-independent aPE antibodies. More specifically, 18:1 PE was a preferred antigen for cofactor-dependent aPE, whereas 20:4 PE was the preferred antigen for cofactor-independent IgG aPE. In contrast, cofactor-independent IgM aPE appeared to have a general preference for a more complex PE combination with longer fatty acids and a higher degree of unsaturation. ConclusionThe present data indicated that the outcome of aPE ELISA was dependent on the composition and physicochemical properties of PE antigens. The discovery that aPE antibodies may have different antigenic preferences could shed light on the nature of their binding interactions.

Influence of Phosphatidylethanolamine Concentration and Composition on the Detection of Antiphosphatidylethanolamine Antibodies by ELISA.

Accumulating evidence supports a positive correlation between the presence of antiphosphatidylethanolamine (aPE) autoantibodies and clinical symptoms of antiphospholipid syndrome (APS). However, there is a lack of standardized ELISA-based method for detecting aPE. The current study was conducted to investigate the dependence of aPE ELISA on lipid concentration and composition of PE antigens. A range of ELISA conditions were examined by varying the concentrations of egg PE and by substituting egg PE with combinations of synthetic DOPE and DSPE. The physical properties of the synthetic PE species were also characterized. Our data indicated that there are different optimal PE concentrations for conducting ELISA assays for cofactor-dependent and cofactor-independent aPEs. In addition, using a two-component synthetic lipid system, we demonstrated aPE ELISA readouts can be modulated to approach the performance level of egg PE, which is currently the most commonly used PE antigen. These data raised the possibility of ultimately replacing natural PE antigens with a blend of defined synthetic lipid species, thus overcoming a known variable factor in aPE detection. The outcome of this study will help pave the way to developing a standardized aPE test.

Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients

The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate. To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients. 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE's criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS's criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive "criteria" APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-P2 glycoprotein I antibodies (aβ2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT). Results. Only the aβ2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/ without positive APLAs): median (min; max) 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p<0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aβ2 GPI (IgG and IgM ) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the "non-criteria" APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels. IgG aβ2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the "non-criteria" APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the "non-criteria" APLAs with the antiDNA and complement C3 levels were also observed.

Lien entre trouble du spectre autistique de l’enfant et anticorps antiphospholipides : une étude cas–témoin

To evaluate the association between the presence of antiphospholipid (APL) antibodies and the occurrence of autism spectrum disorder (ASD) in childhood. A prospective, monocentric case-control study from February 2012 to August 2014 comparing the APL antibodies of children with ASD (group 1) and children without ASD (group 2). Group 1 consisted of 44 children with ASD defined by clinical, genetic, metabolic, and morphological criteria. Group 2 consisted of 26 control children without ASD. One of children with ASD (2.3 %) had persistent anticardiolipin (ACL) antibodies, five of them (11.4 %) had persistent APL antibodies, one of them (2.3 %) had antiannexin V (AAV) antibodies, and two of them (4.5 %) had antiphosphatidylethanolamine (APE) antibodies. Two of the control children (7.7 %) had persistent APL antibodies. None of them had persistent ACL, AAV, or APE antibodies. Comparing group 1 and 2 children, no significant difference was found between the presence and the titers of conventional and non conventional antibodies (P<0.05). Furthermore, one mother of an autistic child (3 %) had persistent APL antibodies. ASD had no significant relation with the presence of APL antibodies.

FACTORS ASSOCIATED WITH THE DEEP VEIN THROMBOSIS IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME

Introduction. Patients with antiphospholipid syndrome (APS) may have a large spectrum of thrombotic clinical events (arterial or venous), but the factors that determine the occurrence of specific clinical manifestation has not been clearly established. Objective. The aim of the study was to determine the factors associated with a history of deep vein thrombosis (DVT) in patients with APS. We were especially interested to fi nd an association between the criteria and non-criteria antiphospholipid antibodies (APLAs) and the DVT. Methods. We realized a cross-sectional study, with consecutive enrollment of all patients presented in our department with the diagnosis of APS in the period 2008-2011. From the total of 106 patients for which the demographic, clinical and biological parameters were collected, the assessment of the criteria and non-criteria APLAs was performed in 73 patients. Results. The mean age at inclusion was 44.7 years, the female-to-male ratio 6.6, and the mean APS disease duration 6.7 years. The majority of the patients included presented with secondary APS (70 patients). Lupus anticoagulant was the most frequent immunological marker used to sustain the diagnosis of APS, found positive in 102 patients (96.2%). The recurrent DVT was more frequently observed in patients with primary APS than in those with secondary APS (p = 0.02). No significant association with DVT was found for the clinical parameters traditionally associated with the risk of thrombosis that we have taken into study: smoking, body mass index (BMI), waist circumference and waist-to-hip ratio. We found a positive association between the DVT history and the positivity for the IgM anti-β2 glycoprotein I antibodies [OR (95%CI) = 6.95 (1.36-35.58), p = 0.01]. The titer of IgG antiprothrombin antibodies and IgG antiphosphatidylethanolamine antibodies was higher in patients with previous DVT [3.0 (0.0-151.0) versus 2.0 (0.0-2.0), p = 0.01, respectively 5.0 (1.0-33.0) versus 3.0 (1.0-7.0), p = 0.01]. In the subgroup of patients with secondary APS, the previous DVT was associated only with the positivity for IgM anti-β2 glycoprotein I antibodies [OR (95%) = 13.63 (1.46-127.15), p = 0.02]. In the same subgroup, the levels of IgG anticardiolipin and the IgG antiphosphatidylethanolamine antibodies were higher in patients with previous DVT [2.0 (0.0-64.0) versus 1.0 (0.0-20.0), p = 0.02, respectively 3.0 (0.0-151.0) versus 2.0 (0.0-7.0), p = 0.03]. In patients with primary APS, the titer of IgG antiprothrombin antibodies was significantly higher when DVT history were present [5.0 (1.0-3.0) versus 3.0 (1.0-7.0), p = 0.01. Only the titer of IgG antiprothrombin antibodies was associated with the history of recurrent thrombosis [5.0 (1.0-3.0) versus 3.0 (1.0-7.0), p = 0.01]. Conclusions. In patients with APS, the DVT history was related with the prevalence of the anti-β2 glycoprotein I antibodies, but also with the levels of some non-criteria antibodies, IgG antiprothrombin antibodies and IgG antiphosphatidylethanolamine antibodies. In patients with primary APS, previous DVT is associated only with the titer of IgG antiprothrombin antibodies, whereas in patients with secondary APS, the DVT history were related with the presence of anti-β2 glycoprotein I antibodies and with the titers of both criteria antibodies (IgG anticardiolipin antibodies) and non-criteria antibodies (IgG antiphosphatidylethanolamine antibodies). The risk of recurrent thrombosis was higher in patients with primary APS when compared with those with secondary APS. Only the titers of IgG antiprothrombin antibodies were correlated with recurrent thrombosis.

Association of anti phosphatidyl ethanolamine antibodies and low complement levels in systemic sclerosis patients – results of a cross-sectional study

Some systemic sclerosis (Ssc) patients express antiphospholipid antibodies and their percentage varies within studies in the literature. The particular role of these antibodies in clinical manifestations of Ssc is still unknown. The aim of the study was to examine an extended panel of antiphospholipid antibodies in Ssc patients who did not have any clinical features of antiphospholipid antibody syndrome. A cross-sectional study was designed and 36 consecutive patients with Ssc were recruited. A relatively high proportion of patients (14 patients – 38.9%) had antiphospholipid antibody presence. Most Ssc patients (11 patients – 30.6%) had IgM anti phosphatidyl ethanolamine antibodies. Serum IgM anti phosphatidyl ethanolamine antibodies, IgM anti prothrombin and IgG anti β2 glycoprotein 1 antibodies were associated with low complement levels in Ssc patients. In multivariate analysis, only serum IgM anti phosphatidyl ethanolamine antibodies concentration and serum IgG anti β2 glycoprotein 1 antibodies concentration were independently associated with hypocomplementemia after adjusting for age and gender. No other correlations with Ssc clinical characteristics were found. In conclusion, antiphospholipid antibodies are present in a large proportion of Ssc patients who do not have clinical features or a history of antiphospholipid antibodies. IgM anti phosphatidyl ethanolamine antibodies seem to be more frequent and the dominant antiphospholipid antibody type in the group recruited from the Romanian Ssc population.

Autoantibodies to Factor XII and Kininogen-Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation.

Numerous studies have suggested that factor XII (FXII) deficiency, autoantibodies to FXII (anti-FXII), and antiphosphatidylethanolamine antibodies (aPE) are associated with recurrent pregnancy loss (RPL). aPE in RPL patients recognize the LDC27 peptide of kininogen domain 3. Anti-FXII in RPL patients recognizes the heavy chain of FXII, especially the amino-terminal sequences IPP30 peptide. Previous studies suggested that LDC27 and IPP30 are the responsible sites competing for the same binding site on platelets and inhibiting augmentation of thrombin-induced platelet aggregation. Our aim was to study the influence of antibodies to LDC27 and IPP30 on platelet aggregation. In fifteen healthy volunteers, platelet aggregation induced by γ-thrombin in the presence or absence of antibodies to LDC27 and IPP30 was measured. Sixteen RPL patients who were positive for anti-FXII were measured for spontaneous small platelet aggregate (SSPA) formation. Antibodies to LDC27 and IPP30 markedly increased aggregation of normal platelets stimulated by γ-thrombin. Augmentation of SSPA formation was more frequent in the patients with RPL who were positive for anti-FXII than in the control group (P = 0.003). This study strongly supports the hypothesis that aPE and anti-FXII may cause RPL due to disruption of the normal antithrombotic effects of kininogens and FXII.

Comment on “Associations between the incidence of antiphosphatidylserine and antiphosphatidylethanolamine antibodies and clinical manifestations of systemic lupus erythematosus”. Authors' reply

Comment on “Associations between the incidence of antiphosphatidylserine and antiphosphatidylethanolamine antibodies and clinical manifestations of systemic lupus erythematosus”. Authors' reply

Comment on “Associations between the incidence of antiphosphatidylserine and antiphosphatidylethanolamine antibodies and clinical manifestations of systemic lupus erythematosus”

Comment on “Associations between the incidence of antiphosphatidylserine and antiphosphatidylethanolamine antibodies and clinical manifestations of systemic lupus erythematosus”

Antiphosphatidylethanolamine Antibodies: New Pieces to the Puzzle of the Antiphospholipid Syndrome?

Objective: To show the contribution of antiphosphatidylethanolamine antibodies (aPE) screening in Antiphospholipid antibody syndrome (APS) diagnosis, especially in Antiphosphopholipid Syndrome (SNAPS) patients, based on litterature data. Methods: A comprehensive literature review of English-language articles from January 1st 2000 to December 31th 2014 was performed using PudMed. Keywords used for the search were: seronegative antiphospholipid antibody OR phosphatidylethanolamine function, biosynthesis and physiological roles OR antiphosphatidylethanolamine antibody OR seronegative antiphospholipid syndrome. Results: Although aPE was not included in the Sapporo criteria for the classification of APS, many studies described a significant association between aPE and the main clinical events of APS: thrombosis and obstetrical complications. Conclusion: Because of aPL family’s heterogeneity, it appears necessary to look for non-criteria aPL in order to improve the diagnostic yield in APS, especially in patients with SNAPS. One of the most promising of this heterogeneous aPL family is aPE. Although these molecules may allow early detection of APS, their clinical relevance is still debatable and needs standardized aPE ELISA, in addition to well-designed clinical studies to confirm its diagnostic value, such as the association between recursion of thrombotic events and the presence of aPE.