Predictive factors of psychiatric syndrome in patients with systemic lupus erythematosus.

Introduction: Early detection of neuropsychiatric systemic lupus erythematosus (NPSLE) remains a challenge in clinical settings. Previous studies have found different autoantibodies as markers for NPSLE. This study aimed to describe the distribution of psychiatric syndromes in a group of patients with systemic lupus erythematosus (SLE) and to investigate the association between psychiatric syndromes and specific autoantibodies. Methods: This retrospective study was conducted at a single medical center in China. We reviewed medical records of hospitalized patients with SLE who were consulted by psychiatrists due to potential mental disorders. Results of serum autoantibodies and general laboratory tests were collected. The correlation between clinical variables was examined. Binary logistic regression analyses were used to determine factors related to NPSLE and different psychiatric diagnoses. Results: Among the 171 psychiatric manifestations in 160 patients, 141 (82.4%) were attributed to SLE. Acute confusional state (ACS) had the highest prevalence (57.4%). Anti-cardiolipin (ACL) antibody (X2 = 142.261, p < 0.001) and anti-ß2 glycoprotein I (-ß2GP1) antibody (X2 = 139.818, p < 0.001) varied significantly between groups, with the highest positive rate found in patients with mood disorders (27.3% and 18.2%). SLE disease activity index - 2000 (SLEDAI-2K) score excluding item ACS and item psychosis was a predictor of NPSLE (OR 1.172 [95% CI 1.105 - 1.243]). Conclusions: Disease activity reflected by SLEDAI-2K score is a predictor for NPSLE. Antiphospholipid antibodies are associated with mood disorders in SLE. Further separate investigation of neuropsychiatric disorders is needed in order to better comprehend NPSLE's pathological mechanism.

Recurrent miscarriage and low-titer antiphospholipid antibodies.

OBJECTIVE: To evaluate the clinical features and pregnancy outcomes in patients experiencing recurrent miscarriage (RM) with either low-titer or medium-high titer positivity of antiphospholipid antibodies (aPL). METHODS: A retrospective review of medical records was conducted for patients with aPL positivity and recurrent miscarriage between 2018 and 2022. The clinical features, treatment strategies, outcomes were compared between the patients with low (n = 92) and medium (n = 32) titer of aPL. RESULTS: A total of 118 patients, resulting in 124 obstetric episodes (pregnancies), with a mean age of 33. 15 ± 4.56 and 31.47 ± 4.41 years between the two groups. The low-titer group exhibited a higher frequency of anti-cardiolipin antibodies IgM (P < 0.001), whereas the medium-high titer group demonstrated a higher frequency of anti-ß2-glycoprotein 1 antibodies IgG (P < 0.001) and IgM (P = 0.032). Moreover, the medium-high titer group displayed a significantly elevated erythrocyte sedimentation rate compared to the low-titer group (P < 0.05). In the low-titer group, 71 patients (77.2%) received appropriate treatment, resulting in 48 live births (67.6%) and 23 repeat abortions (32.4%). In the medium-high titer group, 29 patients (90.6%) received relevant treatment, leading to 23 live births (79.3%) and 6 repeat abortions (20.7%). No significant differences were observed in live births or maternal-fetal complications between the two groups (all P > 0.05). CONCLUSION: Noteworthy distinctions in laboratory parameters were identified between the low-titer and medium-high titer groups. However, when appropriately treated, the fetal-maternal outcomes were comparable in both groups. Timely intervention by clinicians is imperative to enhance pregnancy outcomes in patients experiencing recurrent miscarriage with low levels of aPL. Key Points • This study challenges the conventional belief that only the higher antiphospholipid antibodies (aPL) titers directly correlated with worse pregnancy outcomes, which emphasized the importance of patients with low titer positive aPL-positive RM. • The results underscore the need for timely intervention in women with low titer aPL-positive RM, as it leads to favorable maternal-fetal outcomes.

Epidemiology of antiphospholipid syndrome: macro- and microvascular manifestations.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic and non-thrombotic macro- and microvascular manifestations and pregnancy complications in the setting of persistent antiphospholipid antibodies (aPL), namely anticardiolipin antibodies, anti-ß2 glycoprotein-I antibodies and lupus anticoagulant. Four decades after its first description, APS prevalence and incidence are still not completely understood due to the limited number of well-designed, population-based multi-ethnic studies. Furthermore, despite decades of efforts to standardise aPL immunoassays, considerable intraassay and interlaboratory variances in aPL measures still exist. Large multicentre APS cohorts have shown a 10-year survival of ∼91% and the presence of catastrophic APS occurs in about 1% of the entire population, associated with a 50% mortality rate. Clinically, any organ can be affected in the context of large, medium or small vessel (artery and/or vein) thrombosis. Macrovascular thrombosis is the hallmark of the disease and veins are more frequently affected than arteries. Deep vein thrombosis/pulmonary embolism thromboembolic disease is the most common APS manifestation, while stroke and transient ischaemic attack are the most frequent arterial thrombosis events. Myocardial infarction can also occur and contributes to increased mortality in APS. A minority of patients present with thrombosis affecting the intraabdominal organs, including the liver, spleen, small and large bowel, and the kidneys. Microvascular thrombosis, including APS nephropathy, chronic skin ulcers and livedoid vasculopathy represent a diagnostic challenge requiring histologic confirmation. In this narrative review we summarize the available evidence on APS epidemiology, focusing on the description of the prevalence of macro- and microvascular manifestations of the disease.

Anti-phosphatidyl-serine/prothrombin (aPS/PT) antibodies are superior predictors of LAC presence and APS diagnoses: A single center study.

BACKGROUND AND AIMS: Several non-criteria (NC) anti-phospholipid antibodies (APLA) have been proposed as candidates for antiphospholipid antibody syndrome (APS) diagnosis. The objectives of this study were 1) to determine the association of five different NC-APLA with positivity for Lupus anti-coagulant (LAC) and the criteria antibodies anti-cardiolipin (aCL) and anti-beta glycoprotein (aB2GPI), and 2) to assess the ability of NC-APLA to predict LAC presence and clinical APS diagnoses. MATERIAL AND METHODS: Results from 486 patients tested for LAC and APLA were retrieved. Patients were grouped according to LAC and serology positivity into three groups: Single-positives (SP) for LAC, aCL or aB2GPI; Double-positives for aCL and aB2GPI; Triple-positives (TP) for LAC, aCL and aB2GPI. NC-ALPA titers were compared between LAC-positive and negative and APS and non-APS patients. RESULTS: Forty-two of 486 patients were LAC-positive and 28 were diagnosed with APS. All criteria and NC-APLA titers were significantly higher in TP than SP patients. ROC analyses based on LAC status showed highest area under the curve (AUC, 95% CI) for aPS/PT IgG (0.75, 0.65-0.85) and aPS/PT IgM (0.73, 0.63-0.82). Based on APS diagnosis, aPS/PT IgM achieved highest AUC (0.87; 0.79-0.95). CONCLUSION: Anti-phosphatidyl-serine/prothrombin (aPS/PT) antibodies are superior predictors of LAC presence and APS diagnoses.

Antiphospholipid (Hughes) syndrome 40th anniversary.

This article is a celebration of the 40th anniversary of APS, a disease that appears to affect one in 2000 people. The quality of life of patients affected has improved significantly as a result of early diagnosis and effective treatment.

How I diagnose and treat antiphospholipid syndrome in pregnancy.

ABSTRACT: Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by arterial, venous, or microvascular thrombosis, pregnancy morbidities, or nonthrombotic manifestations in patients with persistently positive antiphospholipid antibodies. These antibodies bind cellular phospholipids and phospholipid-protein complexes resulting in cellular activation and inflammation that lead to the clinical features of APS. Our evolving understanding of APS has resulted in more specific classification criteria. Patients meeting these criteria should be treated during pregnancy according to current guidelines. Yet, despite treatment, those positive for lupus anticoagulant have at least a 30% likelihood of adverse pregnancy outcomes. Patients with recurrent early miscarriage or fetal death in the absence of preeclampsia or placental insufficiency may not meet current classification criteria for APS. Patients with only low titer anticardiolipin or anti-ß(2)-glycoprotein I antibodies or immunoglobulin M isotype antibodies will not meet current classification criteria. In such cases, clinicians should implement management plans that balance potential risks and benefits, some of which involve emotional concerns surrounding the patient's reproductive future. Finally, APS may present in pregnancy or postpartum as a thrombotic microangiopathy, a life-threatening condition that may initially mimic preeclampsia with severe features but requires a very different treatment approach.

The estimated prevalence of antiphospholipid antibodies and criteria-antiphospholipid syndrome in subjects with renal thrombotic microangiopathy.

BACKGROUND: While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA. METHODS: We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against ß2-glycoprotein-I (anti-ß2GPI) and lupus anticoagulant (LA) was then calculated. RESULTS: 522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22-56). The estimated prevalence of aCL (IgG/IgM), anti-ß2GPI, (IgG/IgM) and LA was 4.0% (range 3-27), 4.0% (range 3-16) and 18.9% (range 13-25), respectively. APS was diagnosed in 16.3% (range 11-29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study. CONCLUSIONS: This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases.

Unveiling the Link Between Antiphospholipid Antibodies and Cognitive Dysfunction in the Almenara Lupus Cohort.

OBJECTIVE: Cognitive dysfunction is a prevalent manifestation of systemic lupus erythematosus (SLE). There is evidence for the role of antiphospholipid (aPL) antibodies on its etiopathogenesis. Our objective was to identify the association between aPL antibodies and cognitive dysfunction in SLE patients. METHODS: This cross-sectional study included 135 patients evaluated from March 2015 to October 2017 at one center. Cognitive deficit was measured using the NEUROPSI test. Disease activity and damage were ascertained using the SLEDAI-2K (SLE Disease Activity Index 2000) and the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), respectively; aPL antibodies were measured by enzyme-linked immunosorbent assay. The association between cognitive dysfunction and aPL antibodies was evaluated using univariable and multivariable linear regression models adjusted for age, sex, education, socioeconomic status, disease duration, SLEDAI-2K, SDI, mean current dose of prednisone, time of exposure to glucocorticoids, and drug use (immunosuppressants, hydroxychloroquine, aspirin, and warfarin). RESULTS: One hundred thirty-one patients (97.1%) were women; their mean (SD) age was 46.6 (12.5) years; 59 patients (43.7%) had positivity for at least 1 aPL antibody. IgM anticardiolipin (aCL) was positive in 24.5%, IgG in 13.5%, IgM aß2GP1 in 16.8%, IgG anti-ß2 glycoprotein in 24.6%, and the lupus anticoagulant in 5.3%. Ninety patients (66.7%) had some cognitive dysfunction. In the univariable analysis, a significant correlation between the NEUROPSI score and IgM aCL antibodies was found (B = -20.87 [SE, 3.2]; p < 0.001), which remained significant in the multivariable model (B = -13.89 [SE, 3.14]; p < 0.001). CONCLUSIONS: IgM aCL antibodies are associated with cognitive dysfunction in patients with SLE. Larger and longitudinal studies are needed to assess the impact of these findings.

PREVALENCE OF ANTIPHOSPHOLIPID SYNDROME AMONG PREGNANT WOMEN IN LAUTECH TEACHING HOSPITAL OGBOMOSO NIGERIA.

Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by clinical thrombotic events which may be arterial or venous vasculature associated with the presence of antiphospholipid antibodies (aPL) in patient plasma. Majority of the studies done in this part of the world utilized single auto-antibody to phospholipids or phospholipid binding protein which resulted in an underestimation of the actual prevalence of this treatable disease entity. Hence, this study incorporates the use of triple auto-antibodies to determine the prevalence of APS among pregnant women in LAUTECH Teaching Hospital, Ogbomoso. Aim: To determine the prevalence of antiphospholipid syndrome using triple autoantibodies among pregnant women attending LAUTECH Teaching Hospital, Ogbomoso. Methodology: The study was a longitudinal descriptive design that involved eighty pregnant women with pregnancy complications and apparently eighty healthy pregnant women as control. Participants were tested for APS (antibeta-2-glycoprotein one (Antiß2GP1), anticardiolipin antibody (ACA), and lupus anticoagulant (LAC)) at first contact and persistent positivity after twelve-week intervals using the ELISA method. Results: The prevalence of persistent positivity to anti-phospholipids antibodies in this study are 28.8% and 2.5% among the study and control groups respectively. Persistent positivity to ACA was evident in 26.3%, ß2-GP1 in 21.1% and LAC in 16.3% of participants in the study group and ACA (2.5%), ß2-GP1 (1.3%) and LAC (2.5%) in the control group respectively. Persistent positivity to anti-phospholipids syndrome was associated with hypertension and recurrent miscarriage (≥3). Conclusion: Findings in this study revealed that the prevalence of APS among pregnant women with pregnancy complications using triple auto-antibodies was 28.8%, while the prevalence among healthy pregnant women was 2.5%. This indicates an underestimation of the actual prevalence of APS among pregnant women using single or double autoantibody. Hence, triple auto-antibodies screening is advised as a routine screening during pregnancy especially among those with a previous history of pregnancy complications.

[Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages].

OBJECTIVE: To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages. METHODS: In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table. RESULTS: Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-ß2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%. CONCLUSION: Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

Thrombosis and antiphospholipid antibodies in Japanese COVID-19: based on propensity score matching.

Background: Thrombosis is a unique complication of coronavirus disease 2019 (COVID-19). Although antiphospholipid antibodies (aPL) are detected in COVID-19 patients, their clinical significance remains elusive. We evaluated the prevalence of aPL and serum concentrations of beta-2 glycoprotein I (ß2GPI), a major self-antigen for aPL, in Japanese COVID-19 patients with and without thrombosis. Methods: This retrospective single-center nested case-control study included 594 hospitalized patients with COVID-19 between January 2020 and August 2021. Thrombotic complications were collected from medical records. Propensity score-matching method (PSM) (1:2 matching including age, sex, severity on admission, and prior history of thrombosis) was performed to compare the prevalence and titer of aPL (anti-cardiolipin (aCL) IgG/IgM, anti-ß2GPI IgG/IgM/IgA, and anti-phosphatidylserine/prothrombin antibody (aPS/PT) IgG/IgM) and serum ß2GPI concentration. In addition, PSM (1:1 matching including age and sex) was performed to compare the serum ß2GPI concentration between COVID-19 patients and healthy donors. Results: Among the patients, 31 patients with thrombosis and 62 patients without were compared. The prevalence of any aPLs was indifferent regardless of the thrombosis (41.9% in those with thrombosis vs. 38.7% in those without, p =0.82). The positive rates of individual aPL were as follows: anti-CL IgG (9.7% vs. 1.6%, p =0.11)/IgM (0% vs. 3.2%, p =0.55), anti-ß2GP1 IgG (22.6% vs. 9.7%, p =0.12)/IgA (9.7% vs. 9.7%, p =1.0)/IgM (0% vs. 0%, p =1.0), and anti-PS/PT IgG (0% vs. 1.6%, p =1.0)/IgM (12.9% vs. 21.0%, p =0.41), respectively. The aPL titers were also similar regardless of thrombosis. The levels of ß2GPI in COVID-19 patients were lower than those in the healthy donors. Conclusion: Although aPLs were frequently detected in Japanese COVID-19 patients, their prevalence and titer were irrelevant to thrombotic complications. While COVID-19 patients have lower levels of serum ß2GPI than healthy blood donors, ß2GPI levels were indifferent regardless of thrombosis. Although most of the titers were below cut-offs, positive correlations were observed among aPLs, suggesting that the immune reactions against aPL antigens were induced by COVID-19. We should focus on the long-term thromboembolic risk and the development of APS in the aPL-positive patients with high titer or multiple aPLs.

Antiphospholipid antibodies are enriched post-acute COVID-19 but do not modulate the thrombotic risk.

BACKGROUND AND OBJECTIVES: COVID-19-associated coagulopathy, shown to increase the risk for the occurrence of thromboses and microthromboses, displays phenotypic features of the antiphospholipid syndrome (APS), a prototype antibody-mediated autoimmune disease. Several groups have reported elevated levels of criteria and non-criteria antiphospholipid antibodies (aPL), assumed to cause APS, during acute or post-acute COVID-19. However, disease heterogeneity of COVID-19 is accompanied by heterogeneity in molecular signatures, including aberrant cytokine profiles and an increased occurrence of autoantibodies. Moreover, little is known about the association between autoantibodies and the clinical events. Here, we first aim to characterise the antiphospholipid antibody, anti-SARS-CoV-2 antibody, and the cytokine profiles in a diverse collective of COVID-19 patients (disease severity: asymptomatic to intensive care), using vaccinated individuals and influenza patients as comparisons. We then aim to assess whether the presence of aPL in COVID-19 is associated with an increased incidence of thrombotic events in COVID-19. METHODS AND RESULTS: We conducted anti-SARS-CoV-2 IgG and IgA microELISA and IgG, IgA, and IgM antiphospholipid line immunoassay (LIA) against 10 criteria and non-criteria antigens in 155 plasma samples of 124 individuals, and we measured 16 cytokines and chemokines in 112 plasma samples. We additionally employed clinical and demographic parameters to conduct multivariable regression analyses within multiple paradigms. In line with recent results, we find that IgM autoantibodies against annexin V (AnV), ß2-glycoprotein I (ß2GPI), and prothrombin (PT) are enriched upon infection with SARS-CoV-2. There was no evidence for seroconversion from IgM to IgG or IgA. PT, ß2GPI, and AnV IgM as well as cardiolipin (CL) IgG antiphospholipid levels were significantly elevated in the COVID-19 but not in the influenza or control groups. They were associated predominantly with the strength of the anti-SARS-CoV-2 antibody titres and the major correlate for thromboses was SARS-CoV-2 disease severity. CONCLUSION: While we have recapitulated previous findings, we conclude that the presence of the aPL, most notably PT, ß2GPI, AnV IgM, and CL IgG in COVID-19 are not associated with a higher incidence of thrombotic events.

16th International congress on antiphospholipid antibodies task force report on antiphospholipid syndrome laboratory diagnostics and trends.

Classification criteria for antiphospholipid syndrome (APS) require IgG or IgM isotypes of the anticardiolipin (aCL) antibodies, anti-ß2 glycoprotein I (anti-ß2GPI) antibodies, and/or the lupus anticoagulant (LA) to satisfy the laboratory disease definition. Over the past 20 years, non-criteria antiphospholipid antibodies (aPL) directed to other proteins of the coagulation cascade (i.e. prothrombin and/or phosphatidylserine-prothrombin complex) or to some domains of ß2GPI have been proposed. This task force concentrated and reviewed the literature on data including aPS/PT, antibodies to domain 4/5 of ß2GPI and the newly described antibodies to protein/HLA-DR complex. In addition, we discussed testing of LA in the 'new' oral anticoagulants' era and the value of triple positivity in the risk assessment of aPL. The conclusions were presented at a special session during the 16th International Congress on aPL, Manchester, UK, September 2019.

Prevalence, clinical significance, and persistence of autoantibodies in COVID-19.

BACKGROUND: Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. METHODS: We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. RESULTS: A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-ß2Glycoprotein1 antibody (aß2-GPI) in 32 patients, and IgG aß2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aß2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. CONCLUSION: A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation.

Antibodies to Domain I ß2-Glycoprotein 1 in Patients with Antiphospholipid Syndrome and Systemic Lupus Erythematosus.

The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of ß2-glycoprotein 1 (ß2-GP1), IgG anti-ß2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-ß2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-ß2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-ß2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-ß2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-ß2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-ß2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-ß2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-ß2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-ß2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-ß2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-ß2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively).

Haematological and other manifestations in the presence of antiphospholipid antibodies in a multicentric paediatric cohort.

OBJECTIVES: To identify the variables associated with the development of haematological manifestations in the presence of antiphospholipid antibodies (aPLs) in a paediatric cohort. METHODS: We conducted a multicentric retrospective cohort study of children under the age of 18 years. RESULTS: One hundred and thirty-four children were included; 12.2% had at least one thrombotic event (TE) and 67% at least one non-criterion manifestation. Of them, 90% did not develop any TE. Haematological manifestations were the most frequent (42%), followed by neurological (19.8%), cutaneous (17.6%), cardiac (16.8%) and renal (1.5%) manifestations. In those children with haematological disorders, the aPLs positivity rate was: 67.3% LA, 65.6% aß2GPI, 60% aCL, 45.5% single, 23.6% double and 30.9% triple. A univariate analysis showed that children with IgM aCL+, IgM aß2GPI+, triple positivity and with a SLE diagnosis had a significantly higher frequency of haematological manifestations (p<0.05). Finally, a stepwise regression analysis identified IgG aß2GPI positivity [OR 2.91, 95% CI (1.26-6.74), p=0.013], SLE [OR 2.67, 95% CI (1.13-6.3), p=0.026] and LA positivity [OR 2.53, 95% CI (1.08-5.94), p=0.033] as independent risk factors for the development of haematological manifestations. CONCLUSIONS: Non-criteria manifestations and among them haematological disorders, are the most frequent events in the presence of aPLs and/or LA in our paediatric cohort. Children with SLE, LA and/or IgG aß2GPI positivity showed a higher risk of haematological manifestations.

Risk factors for cardiovascular diseases in patients with systemic lupus erythematosus: an umbrella review.

Cardiovascular disease in patients with systemic lupus erythematosus (SLE) remains one of the most common causes of death and is caused by several factors, including both traditional and disease-specific risk factors. We aimed to systematically appraise the evidence of cardiovascular disease risk factors focusing on the SLE population. The protocol for this umbrella review is registered in PROSPERO (registration no. CRD42020206858). A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library from database inception to June 22, 2022, for systematic reviews and meta-analyzes that examined cardiovascular disease risk factors in patients with SLE. Two reviewers independently extracted data and assessed the quality of the included studies using the "Assessing the Methodological Quality of Systematic Reviews 2 (AMSTER 2)" tool. Of the 102 identified articles, nine systematic reviews were included in this umbrella review. All included systematic reviews were assessed as critically low quality according to the AMSTER 2 tool. The traditional risk factors identified in this study were older age, male sex, hypertension, dyslipidemia, smoking, and a family history of cardiovascular disease. SLE-specific risk factors were long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant. This umbrella review identified some cardiovascular disease risk factors in patients with SLE; however, the study quality of all included systematic reviews was critically low. Key Points • We examined the evidence of cardiovascular disease risk factors focusing on patients with systemic lupus erythematosus. • We found that long-term disease duration, lupus nephritis, neurological disorders, high disease activity, organ damage, use of glucocorticoids, azathioprine, and antiphospholipid antibodies, including anticardiolipin antibodies and lupus anticoagulant, were cardiovascular disease risk factors among patients with systemic lupus erythematosus. • The review indicates the need for well-validated and high-quality future reviews that assess major adverse cardiovascular events as an outcome in patients with systemic lupus erythematosus.

Antiphospholipid Antibody Testing for Anti-cardiolipin and Anti-ß2 Glycoprotein I Antibodies Using Chemiluminescence-Based Panels.

Antiphospholipid (antibody) syndrome (APS) is a prothrombotic condition with increased risk for thrombosis and pregnancy-related morbidity. In addition to clinical criteria related to these risks, APS is characterized by the persistent presence of antiphospholipid antibodies (aPL), as detected in the laboratory using a potentially wide variety of assays. The three APS criteria-related assays are lupus anticoagulant (LA), as detected using clot-based assays, and the solid-phase assays of anti-cardiolipin antibodies (aCL) and anti-ß2 glycoprotein I antibodies (aß2GPI), with immunoglobulin subclasses of IgG and/or IgM. These tests may also be used for the diagnosis of systemic lupus erythematosus (SLE). In particular, APS diagnosis/exclusion remains challenging for clinicians and laboratories because of the heterogeneity of clinical presentations in those being evaluated and the technical application and variety of the associated tests used in laboratories. Although LA testing is affected by a wide variety of anticoagulants, which are often given to APS patients to prevent any associated clinical morbidity, detection of solid-phase aPL is not influenced by these anticoagulants, and this thus represents a potential advantage to their application. On the other hand, various technical issues challenge accurate laboratory detection or exclusion of aPL. This report describes protocols for the assessment of solid-phase aPL, specifically aCL and aß2GPI of IgG and IgM class by means of a chemiluminescence-based assay panel. These protocols reflect tests able to be performed on the AcuStar instrument (Werfen/Instrumentation Laboratory). Certain regional approvals may also allow this testing to be performed on a BIO-FLASH instrument (Werfen/Instrumentation Laboratory).

Laboratory Testing for Non-criteria Antiphospholipid Antibodies: Antibodies Toward the Domain I of Beta2-Glycoprotein I (aDI).

Anti-ß2GPI antibodies (aß2GPI) are one of the laboratory criteria for antiphospholipid syndrome (APS), along with lupus anticoagulant (LA) and anticardiolipin antibodies (aCL). A subset of the aß2GPI are the antibodies directed toward the domain I of the ß2GPI (aDI). The aDI are regarded as non-criteria aPL and are among the most studied non-criteria aPL. Antibodies directed against a specific epitope in the domain I (G40-R43) of ß2GPI were shown to be strongly correlated with thrombotic and obstetric events in APS. Many studies illustrated the pathogenic capacity of these antibodies, although with various results, depending on the assay used. The first studies were performed with an in-house ELISA with high specificity for aDI toward the G40-R43 epitope. More recently, a commercial chemiluminescence immunoassay for aDI IgG became obtainable for diagnostic laboratories. Although the added value of aDI on top of the criteria aPL is not clear, with opposing findings in literature, the assay might help in the diagnosis of APS, identifying the patients at risk since aDI are frequently present with high titers in triple-positive patients (positive for LA, aß2GPI, and aCL). aDI can be used as a confirmatory test and is useful for proving the specificity of the aß2GPI antibodies. In this chapter, the procedure for detecting these antibodies is outlined, using an automated chemiluminescence assay which can be used to determine the presence of IgG aDI in human samples. General guidelines that will facilitate optimal performance of the aDI assay are also provided.