SLE-associated Antiphospholipid Syndrome Research Articles

Comparison of clinical and serological features in thrombotic antiphospholipid syndrome patients, with and without associated systemic lupus erythematosus, followed for up to 42 years: A single centre retrospective study.

To assess the impact of concomitant systemic lupus erythematosus (SLE) on the clinicopathological manifestations of thrombotic antiphospholipid syndrome (APS). This single-centre, retrospective study compared clinical and antiphospholipid antibody (aPL) data from 118 patients, 58 with SLE-associated APS (SLE-APS), and 60 with primary APS. Median follow-up was 13.9 (IQR 7.7-19.3) and 8.6years (3.5-10.6) for the SLE-APS cohort and PAPS cohort, respectively. Age at diagnosis of APS was lower in the SLE-APS cohort (mean 35.9 vs PAPS: 46.7years; p < 0.05). Distribution of aPL subtypes was similar across cohorts. 198 thrombotic events were identified overall (index plus recurrent), with venous thromboembolism (VTE) and arterial thrombosis each occurring in just over half of patients in both cohorts. Microvascular thrombosis (12.1% vs 0%), and a mixed (any combination of venous, arterial and microvascular) thrombotic phenotype (19.0% vs 6.7%, p = 0.05) were more prevalent in SLE-APS patients. Recurrent thrombosis incidence rates (∼0.5 events/10-patient years), and Kaplan-Meier recurrence-free survival after index thrombosis, were similar. In the PAPS cohort, only: (i) triple-aPL-positivity was associated with a significantly higher recurrent thrombosis event rate (incidence rate ratio 2.22, p = 0.03) and lower recurrence-free survival after first thrombosis (log-rank test p = 0.01); (ii) lupus anticoagulant (LA)-positivity was associated with higher prevalance of arterial thrombosis (RR 2.69, p = 0.01), and lower prevlance of VTE (RR 0.48, p < 0.001), versus LA-negativity. Concomitant SLE does not appear to modify long-term recurrent thrombosis risk, or aPL phenotypes, in patients with APS. Triple-aPL-positivity and LA-positive status may have less influence on thrombotic outcomes in patients with SLE-APS compared to PAPS.

Clinical and prognostic significance of antinuclear antibodies in primary antiphospholipid syndrome: A multicenter retrospective study.

The antiphospholipid syndrome (APS) (1) is defined by the development of vascular thrombosis, or pregnancy morbidity in the presence of persistent antiphospholipid antibodies (aPL). Antinuclear antibodies (ANA) can be detected in primary APS patients without any clinical systemic autoimmune disease. The presence of ANA antibodies could confer a specific phenotype in primary APS. To evaluate the characteristics of APS patients with antinuclear antibodies without other autoimmune disease (ANA positive APS patients) in comparison with primary APS without ANA or secondary APS patients with associated systemic lupus erythematosus (SLE). Clinical and biologic data from 195 APS were retrospectively collected and patients were classified as primary APS with positive ANA (ANA-positive APS), primary APS without any ANA (ANA-negative APS), and SLE-associated APS (SLE-APS). Fourty patients (21%) were classified into ANA-positive APS group, 77 (39%) in ANA-negative APS and 78 (40%) in SLE-APS. In ANA-positive APS patients, 20 patients (51%) had arterial thrombosis, 14 (41%) had veinous thrombosis and 19% had obstetrical complications. There was no difference between the three groups for the frequency of thrombotic manifestations and obstetrical complications. ANA-positive APS patients had more non-criteria manifestations than ANA-negative APS (48% versus 25%; P≤0.01). ANA-positive APS had more triple aPL positivity (59% versus 18%; P<0.001) and more thrombosis and obstetrical recurrences (63% versus 36%; P<0.01) in comparison with ANA-negative APS patients. ANA-positive APS had more triple aPL positivity than SLE-APS patients (54% versus 33%; P<0.05). ANA-positive APS and SLE-APS patients had similar clinical manifestations, and recurrences. Despite a limited follow-up (28 months (11-50)) none of the ANA-positive APS develop SLE. Antiplatelet and anticoagulant therapies were similar for the three groups. SLE-APS patients received more immunomodulatory therapies. ANA positivity in patients with APS enables to individualize a subset of patients with a more severe phenotype. Whereas the ANA positivity does not seem to be associated with the risk to develop SLE, prospective studies with a longer follow-up are necessary, in particular to evaluate the effect of additional therapies in this subset of APS.

Bilateral Acute Renal Cortical Necrosis in SLE-Associated Antiphospholipid Syndrome

Acute renal cortical necrosis (ARCN) is a rare cause of acute kidney injury and is characterized by the entire destruction of the renal cortex. We describe a 16-year-old girl with unremarkable personal or family history who presented with acute anuria and dyspnea. Evaluation showed acute kidney injury associated with metabolic acidosis, hyperkalemia, anemia, thrombocytopenia, hematuria, and proteinuria. Serologic tests showed systemic lupus erythematosus-related antiphospholipid syndrome with low serum complement C3 levels, positive anti-double-stranded DNA antibody, positive antiphospholipid antibody, and positive antinuclear antibody. Contrast-enhanced abdominal computed tomography confirmed the presence of ARCN by showing contrasted medulla and a thin layer of subcapsular cortex, but without bilateral enhancement of the renal cortex. This case shows the role of imaging in patients with bilateral ARCN in systemic lupus erythematosus-related antiphospholipid syndrome.

Cutaneous lesions of the digits in systemic lupus erythematosus: 50 cases

The objective of this study was to observe the clinical and pathologic features of digital lesions in a cohort of 50 patients with systemic lupus erythematosus (SLE). Biopsy and pictures of digital lesions were performed in 50 consecutive patients with SLE and digital lesions. A clinical diagnosis of vasculitis was previously suggested in 36% of cases. Pictures were reviewed by three dermatologists and all the tissue sections were analysed by the same pathologist. Files of patients were reviewed retrospectively. Activity of SLE was established according to the lupus activity index (LAI). Digital lesions in SLE were frequently painful (60%) with a finger-pulp inflammation (70%). According to clinical and pathological correlation, five patients had acute cutaneous lupus, five subacute cutaneous lupus, 21 discoid lupus and 15 chilblain lupus. Two patients presented vasculitis: one had an urticarial vasculitis concomitantly to a lupus flare, the other had an erythema elevatum diutinum, independent of SLE evolution. Thrombosis of dermal vessels was present in two patients with SLE-associated antiphospholipid syndrome and in two patients with chilblain lupus. LAI was >1.5 in only seven patients. These results highlight the tendency to clinically overestimate the prevalence of cutaneous vasculitis of the fingers in patients without active SLE. Clinical features of cutaneous lupus of the digits are polymorphous. So, a pathological examination of the lesions is often necessary for diagnosis and proper management.

Acute pulmonary edema, capillaritis and alveolar hemorrhage: pulmonary manifestations coexistent in antiphospholipid syndrome and systemic lupus erythematosus?

Pulmonary capillaritis and alveolar hemorrhage are rare yet serious and life threatening complications of systemic lupus erythematosus (SLE). Pulmonary manifestations of antiphospholipid syndrome (APS) are similar and include, apart from pulmonary embolism and pulmonary hypertension, pulmonary capillaritis, diffuse alveolar hemorrhage and respiratory insufficiency in patients with catastrophic APS. Herein, we described the radiological features of three patients with pulmonary and SLE-associated APS, manifested with pulmonary edema, capillaritis and alveolar hemorrhage. We observed that the radiological features of pulmonary APS shared close resemblance to those of pulmonary SLE. Based on these findings, we conclude that both entities are not only histologically, but also radiologically indistinguishable from each other, suggesting a mutual pathogenetic mechanism. This raises the question of whether some of the reported lupus pneumonitis cases in the past might be manifestations of APS rather than of SLE.

Systemic lupus erythematosus in southern Spain: a comparative clinical and genetic study between Caucasian and Gypsy patients

We evaluated the influence of the hereditary make-up on the development of systemic lupus erythematosus (SLE) in two ethnic groups [Gypsy and white Caucasian Mediterranean (WCM) populations], living in the same geographic area. We compared 81 WCM and 25 Gypsy patients with SLE. The control group consisted of 185 healthy unrelated individuals, 105 WC and 80 Gypsies. In the Gypsy population, the onset of SLE occurred at earlier ages than in the other ethnic group (25.9 versus 32.0 years, P = 0.02), and showed lower SLEDAI peak values (4.9 versus 7.0, P = 0.016). The frequency of joint, kidney, gastrointestinal and eye involvement was significantly lower in Gypsy patients. In contrast, SLE-associated antiphospholipid syndrome, thrombosis and livedo reticularis were more frequent in Gypsies than in the majority ethnic group (WCM). In WCM patients, DRB1* 1303-DQB1*0301 haplotype was associated with SLE (P = 0.001, Pc = 0.038). We found SLE to be associated with DR5 (P = 0.006, Pc = 0.05) in the Gypsy population as well as a protective effect of DPB1*0401 when DR5 was not present (P = 0.008, Pc = 0.032). In conclusion, we found some clinical differences between WCM and Gypsy patients with SLE. Furthermore, HLA associations between HLA-DRB1-DQB1 and SLE were different for Gypsy people.

Genetic polymorphism of murine tissue plasminogen activator associated with antiphospholipid syndrome.

In a subset of patients with systemic lupus erythematosus (SLE), antiphospholipid syndrome characterized by thrombocytopenia, thrombosis, recurrent abortion and antiphospholipid antibodies develops. Male (NZW x BXSB) F1 mice are widely used as a model for SLE-associated antiphospholipid syndrome. Our earlier genetic studies showed that one susceptibility allele for thrombocytopenia and associated IgG platelet-binding autoantibodies in male (NZW x BXSB) F1 mice was linked to the BXSB-type polymorphic microsatellite D8Mit96, located in proximity to the gene Plat for tissue-type plasminogen activator (t-PA). In the present studies, sequence analyses for structural and promoter regions of Plat revealed a single nucleotide polymorphism encoding a catalytic domain of t-PA, with an amino acid substitution of anionic Glu366 in NZW for a cationic Lys in BXSB. Progeny studies using NZW x (NZW x BXSB) F1 male backcross mice showed that the BXSB Plat allele was significantly associated with high levels of both platelet-binding antibodies and thrombocytopenia. Furthermore, these two traits appeared to be regulated by a complementary effect of two BXSB alleles; one is linked to Plat and the other to the H-2 complex and the gene for plasminogen. Thus, the BXSB-type Plat may be one susceptibility allele for the multigenic antiphospholipid syndrome seen in (NZW x BXSB) F1 mice. Potential mechanisms are discussed.

Multigenic control of lupus-associated antiphospholipid syndrome in a model of (NZW x BXSB) F1 mice.

In a subset of systemic lupus erythematosus (SLE) patients, antiphospholipid syndrome, characterized by occurrence of anti-cardiolipin (CL) antibodies, thrombocytopenia, thrombosis and recurrent intrauterine fetal death occurs. Male (NZW x BXSB)F1 mice, carrying the BXSB Yaa gene, serve as a model for SLE-associated antiphospholipid syndrome. Using microsatellite markers in the NZW x (NZW x BXSB)F1 backcross male progeny, we mapped BXSB alleles contributing to the generation of anti-CL antibodies, platelet-binding antibodies, thrombocytopenia and myocardial infarction. Generation of each disease character was controlled by two major independently segregating dominant alleles, i.e. those on chromosomes (Chr.) 4 and 17 for anti-CL antibodies, Chr. 8 and 17 for both anti-platelet antibodies and thrombocytopenia and, to our surprise, Chr. 7 and 14 for myocardial infarction, and that a combination of the two alleles appeared to produce full expression of each character, as a complementary gene action. The alleles on Chr. 17 linked to the above three characters were all mapped in close proximity to the H-2 complex. Therefore, no single factor such as anti-CL antibodies can explain the pathogenesis of SLE-associated antiphospholipid syndrome. Rather, a combination of susceptibility alleles such as described here, along with additional modifying loci, i.e. BXSB Yaa and some from NZW, characterizes unique SLE features in male (NZW x BXSB) F1 mice. There are potentially important candidate genes which may be linked to the syndrome.

Lack of cross-reaction between antibodies to beta2-glycoprotein-I and oxidized low-density lipoprotein in patients with antiphospholipid syndrome.

Previous studies have shown a cross-reaction between anticardiolipin and anti-oxidized low-density lipoprotein (LDL) antibodies in patients with the antiphospholipid syndrome (APS). The aim was to investigate the existence of a cross-reaction between anti-beta2-glycoprotein-I (beta2-GP-I) and anti-oxidized LDL antibodies in a group of APS patients. Ninety-three patients with APS were included in the study; 47 of these patients were diagnosed as primary APS, while the rest (46 patients) fulfilled criteria for the classification of systemic lupus erythematosus (SLE). All patients were positive for the IgG isotype of anticardiolipin antibodies (aCL). Twelve (26%) SLE-associated APS and 14 (29.7%) primary APS patients had raised concentrations of IgG antibodies to oxidized LDL. There was no correlation between anti-beta2-GP-I and anti-oxidized LDL antibodies. Inhibition experiments showed no cross-reaction either between anti-beta2-GP-I and anti-oxidized LDL antibodies, or between anti-beta2-GP-I and anti-native LDL antibodies. Our study suggests that the presence of both anti-beta2-GP-I and anti-oxidized LDL antibodies in patients with APS is not due to the structural similarity and consequent cross-reaction, and that they are two different populations of antibodies directed against different antigens.