Publications by authors named "Cecilia Nalli"

32 Publications

Low Preconception Complement Levels Are Associated with Adverse Pregnancy Outcomes in a Multicenter Study of 260 Pregnancies in 197 Women with Antiphospholipid Syndrome or Carriers of Antiphospholipid Antibodies.

Biomedicines 2021 Jun 11;9(6). Epub 2021 Jun 11.

Lupus Clinic, Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, 00185 Rome, Italy.

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers' pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed ( = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss ( = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines9060671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230784PMC
June 2021

The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Children's Outcome.

Front Pharmacol 2021 18;12:626258. Epub 2021 Mar 18.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Brescia, Italy.

The management of reproductive issues in women with inflammatory arthritis has greatly changed over decades. In the 1980-1990s, women with refractory forms of arthritis were either not able to get pregnant or did choose not to get pregnant because of their disabling disease. Hence, the traditional belief that pregnancy can induce a remission of arthritis. The availability of biologic agents has allowed a good control of aggressive forms of arthritis. The main topic of discussion during preconception counselling is the use of drugs during pregnancy and breastfeeding. Physicians are now supported by international recommendations released by the European League Against Rheumatism and the American College of Rheumatology, but still they must face with cultural reluctance in accepting that a pregnant woman can take medications. Patient-physician communication should be centered on the message that active maternal disease during pregnancy is detrimental to fetal health. Keeping maternal disease under control with drugs which are not harmful to the fetus is the best way to ensure the best possible outcome for both the mother and the baby. However, there might be concerns about the influence of the exposure to medications on the newborn's health conditions. Particularly, studies suggesting an increased risk of autism-spectrum-disorders in children born to women with rheumatoid arthritis has raised questions about neuropsychological impairment in the offspring of women with chronic arthritis. As a multidisciplinary group of rheumatologists and child neuropsychiatrists, we conducted a study on 16 women with chronic forms of arthritis whose diagnosis was determined before pregnancy and their 18 school-age children. The children underwent a complete neurological examination and validated tests/questionnaires. Behavioral aspects of somatization and anxiety/depression (internalizing problem) or an "adult profile" were found in nearly one third of children. Children at a high risk of neurodevelopmental problems were born to mothers with a longer history of arthritis and were breastfeed for less than 6 months of age or were not breastfeed at all. No association was found with other maternal characteristics such as autoantibody existence and disease activity during and after the pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.626258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013697PMC
March 2021

Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals.

Clin Rev Allergy Immunol 2021 Mar 16. Epub 2021 Mar 16.

Department of Medicine, Rheumatology Unit, University of Perugia, Piazzale Gambuli 1, 06132, Perugia, Italy.

The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12016-021-08857-2DOI Listing
March 2021

Neuropsychiatric Outcome of Children Born to Women With Systemic Lupus Erythematosus and Exposed to Azathioprine: A Case-Control Study.

Front Pharmacol 2020 16;11:613239. Epub 2020 Dec 16.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

The long-term outcome of children born to SLE mothers still represents a controversial topic in literature, with some studies reporting a possible increased prevalence of different neurologic and psychiatric diseases (NPD), including neurodevelopmental disorders (ND), and in particular learning disorders (LD). Different risk factors have been advocated, such as the exposure to auto-antibodies and drugs, particularly Azathioprine (AZA). A case-control study was designed to compare pregnancies treated with AZA (cases) with those not treated with AZA (controls). All the pregnancies had been prospectively followed in two Italian centers. The match was based upon renal involvement, antiphospholipid (aPL) status, maternal age at pregnancy (±5 years) and child's age at the time of the study (±2 years). SLE mothers were interviewed by a telephone survey, particularly focused on the presence of a certified NPD in their children ≥6 years of age. Twenty-seven cases and 65 controls were similar in terms of demographic, immunological and clinical features, except for a higher rate of SLE flares during pregnancy in cases (22.2% vs. 10.8%, :0.191). The 92 children had a mean age of 14.0 years at the time of the survey; 11 had at least one NPD (12.0%). The frequency of each single NPD was similar to that of the general pediatric population and no association was found with either the exposure to AZA, or other specific factors (auto-antibodies, disease activity, obstetric complications, prematurity). The long-term neuropsychiatric outcome of the children born to SLE mothers did not show neither an increased frequency of NPD as compared to the general pediatric population nor a specific pattern of NPD. The exposure to AZA was not associated with the development of NPD in this case-control study of prospectively-followed pregnancies. NPD are complex conditions and large prospective studies are needed to capture the wide range of variables that may contribute to their development in the offspring of SLE women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.613239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772243PMC
December 2020

Antiphospholipid Antibody Profile Stability Over Time: Prospective Results From the APS ACTION Clinical Database and Repository.

J Rheumatol 2021 Apr 1;48(4):541-547. Epub 2020 Sep 1.

D. Erkan, MD, MPH, Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Weill Cornell Medicine, New York, New York, USA.

Objective: The APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine (1) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and (2) predictors of unstable aPL profiles over time.

Methods: A clinically meaningful aPL profile was defined as positive lupus anticoagulant (LAC) test and/or anticardiolipin (aCL)/anti-β glycoprotein-I (anti-β-GPI) IgG/M ≥ 40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis.

Results: Of 472 patients with clinically meaningful aPL profile at baseline (median follow-up 5.1 yrs), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable, and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate ( = 0.906) and multivariable analysis ( = 0.790). Baseline triple aPL positivity decreased (OR 0.25, 95% CI 0.10-0.64, = 0.004) and isolated LAC test positivity increased (OR 3.3, 95% CI 1.53-7.13, = 0.002) the odds of an unstable aPL profile over time.

Conclusion: Approximately 80% of our international cohort patients with clinically meaningful aPL profiles at baseline remain stable at a median follow-up of 5 years; triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.200513DOI Listing
April 2021

Disease course and obstetric outcomes of pregnancies in juvenile idiopathic arthritis: are there any differences among disease subtypes? A single-centre retrospective study of prospectively followed pregnancies in a dedicated pregnancy clinic.

Clin Rheumatol 2021 Jan 18;40(1):239-244. Epub 2020 Sep 18.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, Brescia, Italy.

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-020-05404-wDOI Listing
January 2021

The pathogenic role of circulating Hashimoto's Thyroiditis-derived TPO-positive IgG on fetal loss in naïve mice.

Am J Reprod Immunol 2021 01 20;85(1):e13331. Epub 2020 Sep 20.

Laboratory of the Mosaic of Autoimmunity, Saint Petersburg State University, Saint Petersburg, Russia.

Problem: Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies.

Aim: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model.

Method Of Study: Naïve ICR female mice, infused intravenously with 100 μg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti-TPO-positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO-positive IgG-treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti-TPO-positive IgG samples.

Conclusion: The current study shows in the first time, a direct proof of concept, on the association of human TPO-positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.13331DOI Listing
January 2021

"APS pregnancy - The offspring".

Lupus 2020 Oct 4;29(11):1336-1345. Epub 2020 Aug 4.

Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

Background: Antiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates.

Methods: A keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS).

Results: Offspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported.

Conclusions: The limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0961203320947154DOI Listing
October 2020

Cluster analysis for the identification of clinical phenotypes among antiphospholipid antibody-positive patients from the APS ACTION Registry.

Lupus 2020 Jul 23:961203320940776. Epub 2020 Jul 23.

Barbara Volcker Centre for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Cornell Medicine, New York, USA.

Objective: This study aimed to use cluster analysis (CA) to identify different clinical phenotypes among antiphospholipid antibodies (aPL)-positive patients.

Methods: The Alliance for Clinical Trials and International Networking (APS ACTION) Registry includes persistently positive aPL of any isotype based on the Sydney antiphospholipid syndrome (APS) classification criteria. We performed CA on the baseline characteristics collected retrospectively at the time of the registry entry of the first 500 patients included in the registry. A total of 30 clinical data points were included in the primary CA to cover the broad spectrum of aPL-positive patients.

Results: A total of 497 patients from international centres were analysed, resulting in three main exclusive clusters: (a) female patients with no other autoimmune diseases but with venous thromboembolism (VTE) and triple-aPL positivity; (b) female patients with systemic lupus erythematosus, VTE, aPL nephropathy, thrombocytopaenia, haemolytic anaemia and a positive lupus anticoagulant test; and (c) older men with arterial thrombosis, heart valve disease, livedo, skin ulcers, neurological manifestations and cardiovascular disease (CVD) risk factors.

Conclusions: Based on our hierarchical cluster analysis, we identified different clinical phenotypes of aPL-positive patients discriminated by aPL profile, lupus or CVD risk factors. Our results, while supporting the heterogeneity of aPL-positive patients, also provide a foundation to understand disease mechanisms, create new approaches for APS classification and ultimately develop new management approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0961203320940776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216235PMC
July 2020

Infertility in women with systemic autoimmune diseases.

Best Pract Res Clin Endocrinol Metab 2019 12 2;33(6):101369. Epub 2019 Dec 2.

Department of Obstetrics and Gynecology of I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

Infertility consists by definition in" failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse" while the term subfertility means a delay to achieve pregnancy. Several factors can contribute to infertility or subfertility in patients with systemic autoimmune diseases. The association of systemic autoimmune conditions with endometriosis, celiac disease and thyroid autoimmunity that are well known causes of infertility and/or subfertility need to be taken in consideration when difficulties in the onset of pregnancy is reported. The majority of the used antirheumatic drugs do not interfere with fertility. However, the use of cyclophosphamide, limited to severe disease, can provoke premature ovarian failure; to preserve fertility a preventive treatment is available. Nonsteroidal anti-inflammatory drugs can cause temporary infertility and corticosteroids are associated to a prolonged time to pregnancy in some rheumatic diseases. Data on the association of antiphospholipid antibodies (aPL) with infertility are still debated but in general an increased rate of aPL is described patients undergoing medically assisted reproductive techniques. In systemic lupus erythematosus aPL and other autoantibodies (i.e. anti-oocytes) can contribute to the infertility of some patients. Subfertility, rather than infertility, is observed in patients with rheumatoid arthritis; the particular physical conditions of these women can also account for this. Physicians should not forget the patients' age, that is mandatory in order to preserve their chance to have children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.beem.2019.101369DOI Listing
December 2019

Long-term outcome of children born from mothers with autoimmune diseases.

Best Pract Res Clin Obstet Gynaecol 2020 Apr 13;64:107-116. Epub 2019 Nov 13.

Rheumatology and Immunology Unit, Department of Clinical and Experimental Sciences, University of Brescia and ASST Spedali Civili of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.

Autoimmune diseases often affect young women and this may represent a problem in family planning. Pregnancies in these patients may carry several complications but nowadays the continued amelioration in treatment and management has greatly improved the pregnancy outcome. The main concern of these women obviously is the short- and long-term outcome of their children. A child born from a woman with autoimmune disease is potentially exposed in utero to maternal autoantibodies, cytokines, and drugs, and each item could impair his or her development. In addition, the maternal genetic heritage can favor autoimmunity. All these items could have a role, for example, in the development of autoimmune diseases (the same as the mother or different ones) or neurological disorders. Data in literature are controversial. This review will gather the available data possibly providing a useful tool for counseling future mothers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpobgyn.2019.11.003DOI Listing
April 2020

Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry.

Rheumatology (Oxford) 2020 06;59(6):1306-1314

Clinical Research Unit, Althaia Healthcare University Network of Manresa, University of Vic - Central University of Catalonia, Barcelona.

Objectives: To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS).

Methods: This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome.

Results: A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C).

Conclusion: Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/kez419DOI Listing
June 2020

Autoimmune diseases and pregnancy.

Best Pract Res Clin Endocrinol Metab 2019 12 11;33(6):101322. Epub 2019 Sep 11.

Department of Obstetrics and Gynecology of I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

Pregnancy in autoimmune diseases remains an argument of debate. In last years great improvements were done and with the correct medical support women with disease such as Systemic Lupus Erythematosus or Antiphospholipid Syndrome can afford a pregnancy and have healthy babies. The starting point is a good counselling. Women should be informed about risks that can occur taking some medications while pregnant and, on the other hand, that there are medications that can be safety assumed during pregnancy. Furthermore, there are known maternal risks factor such as the presence of antiphospholipid antibodies or anti-Ro/SSA antibodies that must be carefully manage by both rheumatologists and obstetrics. In addition, also disease activity during pregnancy can represent an issue. For all these reason, a multidisciplinary approach is mandatory in order to give our patients an optimal medical support, before, during and after pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.beem.2019.101322DOI Listing
December 2019

The comparison of real world and core laboratory antiphospholipid antibody ELISA results from antiphospholipid syndrome alliance for clinical trials & international networking (APS ACTION) clinical database and repository analysis.

Thromb Res 2019 Mar 18;175:32-36. Epub 2019 Jan 18.

Academic Department of Vascular Surgery, Cardiovascular School of Medicine & Sciences, King's College London, UK.

Background: The APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies (aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network.

Objective: To assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β-glycoprotein-I antibody (aβGPI) ELISA testing results.

Methods: Patients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available.

Results: 497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen's kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβGPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβGPI).

Conclusions: The results of inclusion for aCL and aβGPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβGPI results showed very good categorical agreement. This agreement increased when considering high titer (>40 units) samples. APS ACTION is a reliable and useful research resource for APS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2019.01.010DOI Listing
March 2019

"Disease knowledge index" and perspectives on reproductive issues: A nationwide study on 398 women with autoimmune rheumatic diseases.

Joint Bone Spine 2019 07 21;86(4):475-481. Epub 2018 Dec 21.

Rheumatology Unit, Department of Medicine, University of Perugia, Piazzale Gambuli, 1, 06132 Perugia, Italy.

Objective: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age.

Methods: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149).

Results: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning.

Conclusion: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbspin.2018.12.002DOI Listing
July 2019

Antiphospholipid syndrome: state of the art on clinical practice guidelines.

RMD Open 2018 18;4(Suppl 1):e000785. Epub 2018 Oct 18.

Liga Portuguesa Contra as Doenças Reumáticas, Núcleo Síndrome de Sjögren, Lisbon, Portugal.

Antiphospholipid syndrome (APS) is a rare disease characterised by venous and/or arterial thrombosis, pregnancy complications and the presence of specific autoantibodies called antiphospholipid antibodies. This review aims to identify existing clinical practice guidelines (CPG) as part of the ERN ReCONNET project, aimed at evaluating existing CPGs or recommendations in rare and complex diseases. Seventeen papers providing important data were identified; however, the literature search highlighted the scarceness of reliable clinical data to develop CPGs. With no formal clinical guidelines in place, diagnosis and treatment of APS is largely based on consensus and expert opinion. Patients' unmet need refers to the understanding of the disease and its clinical picture and implications, the need of education for patients, family members and healthcare providers, as well as to the development of monitoring pathways involving multiple healthcare providers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/rmdopen-2018-000785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203101PMC
October 2018

Anti-phospholipid IgG antibodies detected by line immunoassay differentiate patients with anti-phospholipid syndrome and other autoimmune diseases.

Auto Immun Highlights 2018 May 29;9(1). Epub 2018 May 29.

University of Brescia, Brescia, Italy.

Purpose: Anti-phospholipid antibodies (aPL) analyzed by line immunoassay (LIA) can recognize beta-glycoprotein I (βGPI) domain 1 (D1) epitopes depending on βGPI binding to distinct phospholipids. The aPL LIA was compared with consensus ELISA to investigate whether both techniques can discriminate anti-phospholipid syndrome (APS) patients from aPL-positive, systemic autoimmune rheumatic diseases (SARD) patients without clinical symptoms of APS and controls.

Methods: Thirty-four APS patients (14 arterial/venous thrombosis, 16 pregnancy morbidity, and 4 both), 41 patients with SARD lacking clinical APS criteria but demonstrating positivity for anti-βGPI (aβGPI) IgG, and 20 healthy subjects (HS) were tested for aPL to cardiolipin (aCL), phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol (aPG), phosphatidylinositol, phosphatidylserine, βGPI, prothrombin, and annexin V by LIA. Samples were also tested for aCL, aβGPI, aβGPI-domain 1 (aD1), and aβGPI-domains 4-5 (aD4-5) by ELISA and for lupus anti-coagulant.

Results: Comparison of LIA with ELISA revealed a good agreement for the consensus criteria aPL aβGPI and aCL IgG (kappa = 0.69, 0.68, respectively) and a moderate agreement for IgM (kappa = 0.52, 0.49, respectively). Regarding ELISA, aD1/aD4-5 demonstrated the best performance of differentiating APS from asymptomatic SARD [area under the curve (AUC): 0.76]. aPG IgG had the best performance by LIA (AUC: 0.72) not significantly different from aD1/aD4-5. There was a good agreement for aPG IgG with aD1/aD4-5 (kappa = 0.71).

Conclusions: aD1/aD4-5 (ELISA) and aPG IgG (LIA) differentiate APS from SARD patients. PG appears to interact with βGPI of APS patients and exposes D1 thereof for disease-specific aPL binding in LIA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13317-018-0106-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975024PMC
May 2018

Beyond thrombosis: Anti-β2GPI domain 1 antibodies identify late pregnancy morbidity in anti-phospholipid syndrome.

J Autoimmun 2018 06 14;90:76-83. Epub 2018 Feb 14.

Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy; Experimental Laboratory of Immunological and Rheumatologic Researches, IRCCS Istituto Auxologico Italiano, Via Zucchi 18, 20095 Cusano Milanino, Milan, Italy; Department of Rheumatology, ASST Istituto Gaetano Pini & CTO, Piazza Cardinal Ferrari, 1 20122 Milan, Italy. Electronic address:

Antibodies against β2 glycoprotein I (anti-β2GPI) have been identified as the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the most relevant epitope is a cryptic and conformation-dependent structure on β2GPI domain (D) 1. Anti-β2GPI domain profiling has been investigated in thrombotic APS, leading to the identification of antibodies targeting D1 as the main subpopulation. In contrast, scarce attention has been paid to obstetric APS, hence this study aimed at characterizing the domain reactivity with regards to pregnancy morbidity (PM). To this end, 135 women with persistently positive, medium/high titre anti-β2GPI IgG, without any associated systemic autoimmune diseases and at least one previous pregnancy were included: 27 asymptomatic carriers; 53 women with obstetric APS; 20 women with thrombotic APS; and 35 women with both thrombotic and obstetric complications. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a research ELISA assay, respectively (QUANTA Flash β2GPI Domain 1 IgG and QUANTA Lite β2GPI D4/5 IgG, Inova Diagnostics). Positivity for anti-D1 antibodies, but not anti-D4/5 antibodies, was differently distributed across the 4 subgroups of patients (p < 0.0001) and significantly correlated with thrombosis (χ2 = 17.28, p < 0.0001) and PM (χ2 = 4.28, p = 0.039). Patients with triple positivity for anti-phospholipid antibodies displayed higher anti-D1 titres and lower anti-D4/5 titres compared to women with one or two positive tests (p < 0.0001 and p = 0.005, respectively). Reactivity against D1 was identified as a predictor for PM (OR 2.4, 95% confidence interval [CI] 1.2-5.0, p = 0.017); in particular, anti-D1 antibodies were predictive of late PM, conveying an odds ratio of 7.3 (95% CI 2.1-25.5, p = 0.022). Positivity for anti-D1 antibodies was not associated with early pregnancy loss. Anti-D4/5 antibodies were not associated with clinical APS manifestations. As a whole, our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis, but also with late PM, while positive anti-D4/5 antibodies are not predictive of thrombosis or PM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaut.2018.02.002DOI Listing
June 2018

A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus.

J Autoimmun 2016 11 2;74:106-117. Epub 2016 Jul 2.

Rheumatology and Clinical Immunology, Spedali Civili of Brescia, Italy; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Electronic address:

Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaut.2016.06.016DOI Listing
November 2016

Antirheumatic drugs and reproduction in women and men with chronic arthritis.

RMD Open 2015 15;1(Suppl 1):e000048. Epub 2015 Aug 15.

Rheumatology and Clinical Immunology Unit , Spedali Civili di Brescia , Brescia , Italy ; Department of Clinical and Experimental Sciences , University of Brescia , Brescia , Italy.

The impact of rheumatic disease on fertility and reproduction can be remarkable. Many disease-related factors can influence patients' sexual functioning, perturb fertility and limit family planning. Antirheumatic pharmacological treatment can also have a crucial role in this field. Proper counselling, preferably provided by a multidisciplinary team of rheumatologists, obstetricians, gynaecologists and neonatologists, is recommended for patients taking antirheumatic drugs, not only at the beginning, but also during the course of treatment. Paternal exposure to antirheumatic drugs was not found to be specifically associated with congenital malformation and adverse pregnancy outcome, therefore discontinuation of these drugs while planning for conception should be weighed against the risk of disease flare. Drugs in Food and Drug Administration (FDA) category 'X' should be withdrawn in a timely manner in women who desire a pregnancy. Meanwhile, disease control can be achieved with anti-tumour necrosis factor (TNF)-α agents, which are not teratogenic drugs. If maternal disease control is permissive, they can be stopped as soon as the pregnancy test turns positive and be resumed during pregnancy in case of a flare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/rmdopen-2015-000048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632146PMC
November 2015

The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation.

J Immunol Res 2015 22;2015:638129. Epub 2015 Jun 22.

Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany.

To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/638129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491572PMC
March 2016

Efficacy and safety of off-label use of rituximab in refractory lupus: data from the Italian Multicentre Registry.

Clin Exp Rheumatol 2015 Jul-Aug;33(4):449-56. Epub 2015 Jun 8.

Department of Medicine-DIMED, Division of Rheumatology, University of Padova, Italy.

Objectives: To evaluate the efficacy and safety of rituximab (RTX) in patients with systemic lupus erythematosus (SLE) refractory to standard therapy in the clinical practice setting.

Methods: 145 SLE patients (ACR criteria) were treated with RTX in 11 Italian Centres: 118 with two infusions (1 g), two weeks apart; 27 with 4 infusions (375 mg/m2), one week apart, followed in 10 cases by two further doses, after 1 and 2 months. Systemic complete response (CR) was defined as European Consensus Lupus Activity Measurement (ECLAM) score ≤1 and partial response (PR) as 1< ECLAM ≤3. Renal CR (RCR) and renal PR (RPR) were defined according to EULAR recommendations for management of lupus nephritis.

Results: Data from 134 (92.4%) patients were available. The mean±SD follow-up was 27.3±18.5 months. After the first course of RTX, CR or PR were observed in 85.8% and CR in 45.5% of cases; RCR or RPR in 94.1% and RCR in 30.9% of patients after 12-month follow-up. Disease flares occurred in 35.1% and renal flares in 31.2% of patients during observational period. Among patients retreated, CR or PR were observed in 84.4% and CR in 57.8% of cases. Adverse events, infections, and infusion reactions occurred after first RTX course in 23.8%, 16.4%, and 3.8% of patients and after retreatment in 33.3%, 22.2% and 11.1%, respectively. No severe infusion reactions or deaths occurred.

Conclusions: Data from Italian multicentre RTX Registry confirmed the efficacy and safety of RTX in SLE patients refractory to standard treatment in clinical practice setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2015

Clinical characterization of antiphospholipid syndrome by detection of IgG antibodies against β2 -glycoprotein i domain 1 and domain 4/5: ratio of anti-domain 1 to anti-domain 4/5 as a useful new biomarker for antiphospholipid syndrome.

Arthritis Rheumatol 2015 May;67(8):2196-204

University of Brescia, Brescia, Italy.

Objective: It has been suggested that only antibodies against domain 1 (D1) of β2 -glycoprotein I (β2 GPI) are pathogenic and diagnostic. The role of antibodies against other β2 GPI domains is still debated. This study was undertaken to evaluate the clinical relevance of domain specificity profiling of anti-β2 GPI IgG antibodies in antiphospholipid syndrome (APS) patients and in control groups of patients with systemic autoimmune rheumatic diseases and in asymptomatic antiphospholipid antibody (aPL) carriers.

Methods: We evaluated 159 subjects with persistently positive, medium or high-titer anti-β2 GPI IgG, including 56 patients with thrombotic (obstetric or nonobstetric) primary APS, 31 women with obstetric primary APS, 42 aPL-positive patients with systemic autoimmune rheumatic diseases, and 30 asymptomatic aPL carriers. One hundred healthy donors were included. Anti-β2 GPI D1 and D4/5 IgG were tested on research enzyme-linked immunosorbent assays containing recombinant β2 GPI domains.

Results: As compared to other groups, aPL carriers displayed higher frequency/titer of anti-D4/5 IgG. Unlike anti-D4/5, anti-D1 IgG antibodies were more frequent and at higher titer in triple than in single or double aPL-positive subjects. An anti-D1 to anti-D4/5 ratio of ≥1.5 was predictive of systemic autoimmunity (odds ratio 3.25 [95% confidence interval 1.45-7.49], P = 0.005). Neither anti-D1 nor anti-D4/5 antibodies were associated with APS clinical criteria.

Conclusion: Anti-D1 IgG is the preferential specificity not only in vascular and obstetric primary APS, but also in patients with systemic autoimmune rheumatic disease with no clinical features of APS. Conversely, aPL carriers do not have a polarized profile toward D1. Combined testing for anti-β2 GPI IgG with different domain specificity allows a more accurate aPL profiling, with polarization toward anti-D1 IgG as a possible fingerprint of systemic autoimmunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.39187DOI Listing
May 2015

The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 247 consecutive cases.

Autoimmun Rev 2015 May 31;14(5):387-95. Epub 2014 Dec 31.

Obstetric and Gynaecolgy Department, Vall d'Hebron University Hospital, Universitat Autonòma, Barcelona, Spain.

Aim: To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS).

Methods: The European Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported.

Results: 338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment and 17 (31%) did not. 177/247 (72%) women were put on heparin plus LDA. Thrombosis appeared in two during pregnancy and in 14 during the puerperium. 7 (3%) women evolved to complete SLE.

Conclusions: OAPS shows differential characteristics than classical APS. All laboratory test categories are needed to avoid false-negative diagnoses. In some cases, complement levels could act as a serological marker. OAPS has very good foetal-maternal outcomes when treated. Thrombosis and progression to SLE in mothers with OAPS are scarce compared with "classical APS", suggesting that they have different aPL-mediated pathogenic mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.autrev.2014.12.010DOI Listing
May 2015

Pregnancy in antiphospholipid syndrome: can we improve patient management?

Isr Med Assoc J 2014 Oct;16(10):614-5

View Article and Find Full Text PDF

Download full-text PDF

Source
October 2014

Management of recurrent thrombosis in antiphospholipid syndrome.

Curr Rheumatol Rep 2014 Mar;16(3):405

Rheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Brescia, Italy,

One of the challenges of managing patients with antiphospholipid syndrome is the prevention of rethrombosis (secondary prophylaxis). Risk stratification, i.e. traditional cardiovascular and thrombosis risk factors, systemic autoimmune diseases, antiphospholipid antibody profile, and the intensity of anticoagulation are all relevant to the management of APS patients with recurrent thrombosis. The paper will review "state of the art" strategies for optimizing therapy for APS patients with recurrent thrombosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11926-013-0405-4DOI Listing
March 2014

Clinical significance of IgA anti-cardiolipin and IgA anti-β2glycoprotein I antibodies.

Curr Rheumatol Rep 2013 Jul;15(7):343

Rheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.

IgA antiphospholipid antibodies (aPL) are not currently recognized as formal laboratory criteria for the Antiphospholipid Syndrome (APS). This is mainly due to methodological issues (different study designs, use of various non-standardized IgA assays). However, there are experimental data showing the pathogenic role of IgA anti-cardiolipin antibodies (aCL) and IgA anti-β2glycoprotein I antibodies (anti-β2GPI). Isolated IgA aCL are not very common, therefore their testing could be useful in the case of strong suspicion of APS but negative results for other aPL tests. IgA anti-β2GPI seem to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE), with a significant association with thrombotic events. Such a clinical relevance has been recently recognized by the inclusion of these autoantibodies among the aPL tests in the novel SLICC classification criteria for SLE. Emerging interest has been raised by IgA anti-β2GPI against domain 4/5 as a novel subgroup of clinically relevant aPL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11926-013-0343-1DOI Listing
July 2013

Antiphospholipid antibodies mediate autoimmunity against dying cells.

Autoimmunity 2013 Aug 29;46(5):302-6. Epub 2013 May 29.

Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Italy.

The Antiphospholipid Syndrome (APS) is characterized by thrombosis and pregnancy loss, clinical events mediated by pathogenic anti-phospholipid autoantibodies (aPL). β2-glycoprotein I (β2GPI) is the major autoantigens recognized by aPL. β2GPI is a cationic protein that binds to negatively charged surfaces such as those of apoptotic cells. This feature may lead to two major events: i) immunization with β2GPI fosters the Fc-receptor-mediated uptake by antigen presenting cells of apoptotic material decorated with β2GPI and the activation of β2GPI-specific T cells which in turn provide help to β2GPI-specific B cells for the production of anti-β2GPI; ii) apoptotic bodies decorated with β2GPI can be opsonized by anti-β2GPI and shifted towards a pro-inflammatory clearance by macrophages; epitope spread can occur with the generation of autoimmunity against nuclear autoantigens. In the presence of a predisposing genetic background and of a particular cytokine environment (type I interferons), the sequential emergence of autoantibodies can evolve into overt clinical disease. The spectrum of clinical phenotypes of the patients can be modulated by several factors affecting the pathogenicity of anti-β2GPI (e.g. domain specificity). We conclude that dying cells may play a dual role in APS: (I) as immunogen for the induction of aPL (etiology) and (II) as targets of aPL for the chronification of inflammation and the development of autoimmune diseases (pathology).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08916934.2013.783025DOI Listing
August 2013