The value of IgA antiphospholipid testing for diagnosis of antiphospholipid (Hughes) syndrome in systemic lupus erythematosus.

OBJECTIVE: It is recognized that the presence of IgG and IgM anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) is associated with thrombosis in patients with antiphospholipid syndrome (APS). Some reports have shown that testing for IgA anticardiolipin and anti-beta2-glycoprotein antibodies (anti-beta2-GPI) provides extra diagnostic help in patients with APS, while other authors could not support this data. We designed this cross sectional study to determine the prevalence of IgA aCL, anti-beta2-GPI, and antiprothrombin antibodies and to study their clinical significance in a large cohort of patients with systemic lupus erythematosus (SLE). METHODS: This study comprised 134 SLE patients (126 women; median age 37.5 yrs, range 16-72). The median duration of the disease was 9 years, range 0.1-38. Of these, 55 (41%) had a history of thrombotic events: 22 (40%) presented an arterial event, 22 (40%) a venous event, and 11 (20%) both arterial and venous events. Of 49 women who had been pregnant, 18 (37%) gave a history of recurrent pregnancy loss. Thrombocytopenia was present in 14/127 patients (11%). Forty patients (30%) were diagnosed as APS secondary to SLE, 23 (17%) had IgG/M aCL and/or LAC without clinical features of APS, and 71 (53%) were SLE patients who were repeatedly negative for IgG/M aCL or LAC. IgG, IgM, IgA aCL and anti-beta2-GPI were detected by ELISA. Antibodies directed to prothrombin were detected by 2 ELISA using prothrombin coated on irradiated plates (aPT) and phosphatidylserine/prothrombin complex (aPS/PT) as antigen. RESULTS: IgA aCL were found in 18/134 (13%) patients. Of these, 3 (17%) had IgA aCL as well as IgG/M aCL, and 2 (11%) had IgG/M aCL and anti-beta2-GPI. Of the 18 patients positive for IgA aCL, 8 were also positive for LAC. Of these, one (5%) patient had IgA aCL as well as other isotype of aCL, and 7 (39%) patients had both aCL and anti-beta2-GPI. None of these patients had binding of IgA aPT or aPS/PT. Of the entire group of 18 patients, 5 (28%) had IgA aCL as the sole aPL. Four of 5 of these patients were diagnosed as SLE but had no antiphospholipid (aPL) related clinical manifestations. We found no association between the presence of IgA aCL and clinical manifestations of APS. IgA anti-beta2-GPI were found in 8/134 (6%) patients. Of these, one (12.5%) had IgA anti-beta2-GPI as well as IgG/M anti-beta2-GPI and aCL. Of the 8 patients positive for IgA anti-beta2-GPI, 6 (75%) were also positive for LAC. Of these, one (12.5%) patient presented with IgA anti-beta2-GPI along with other isotypes of aCL, and 4 (50%) patients with aCL and other isotype of anti-beta2-GPI. One patient (12.5%) had IgA anti-beta2-GPI along with LAC only, and one patient (12.5%) who was diagnosed as SLE had no aPL related clinical manifestation but had IgA anti-beta2-GPI as the sole aPL. CONCLUSION: IgA aCL and anti-beta2-GPI are found in SLE, usually along with IgG and/or IgM isotypes. Testing for IgA aCL and anti-beta2-GPI is not a helpful screening test and does not contribute to the recognition of APS in SLE. IgA aPT and aPS/PT are not present in patients with SLE, therefore there is no need to test for these antibodies.     

Prevalence and clinical correlates of anti-phospholipid antibodies in South Africans with systemic lupus erythematosus

OBJECTIVE: To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti-beta2-glycoprotein 1 (abeta2GP1), and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, abeta2GP, and aPT of all isotypes, and LA. RESULTS: Positive aCL, abeta2GPI, aPT, and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG abeta2GPI were the commonest aCL (49.1%) and abeta2GPI (47%) isotypes, respectively. IgA abeta2GPI were associated with both a history of thrombosis alone (p<0.05) and a history of any clinical feature, thrombosis, and/or spontaneous abortion of the APS (p<0.05); IgA aCL were associated with a history of any clinical APS event (p<0.05); and abeta2GPI of any isotype were associated with a history of arthritis (p<0.001). CONCLUSION: Our findings provide further evidence that screening for abeta2GPI and IgA aCL isotypes may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for the increased IgA aPL response in SLE patients of African extraction.     

Anticardiolipin, anti-beta(2)-glycoprotein I and antiprothrombin antibodies in black South African patients with infectious disease

OBJECTIVES: To investigate IgG, IgM, and IgA, antiphospholipid antibodies (aPL), against cardiolipin (aCL), beta(2)-glycoprotein I (anti-beta(2)GPI), and prothrombin (anti-PT), in black South African patients with infectious disease. Unlike patients with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS), raised levels of aPL in infectious diseases are not usually associated with thrombotic complications. PATIENTS AND METHODS: Serum samples from 272 patients with a variety of infectious diseases (100 HIV positive, 112 leprosy, 25 syphilis, 25 malaria, and 10 HCV patients) were studied and compared with autoantibody levels in 100 normal controls. All three aPL were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. RESULTS: Raised levels of all three aPL were found in all patient groups studied: aCL in 7%, anti-beta(2)GPI in 6%, and aPT in 43% of 100 HIV patients, in 29%, 89%, and 21% of 112 patients with leprosy, in 8%, 8%, and 28% of 25 patients with syphilis, in 12%, 8%, and 28% of 25 patients with malaria, and in 20%, 30%, and 30% of 10 HCV patients studied, respectively. CONCLUSIONS: The prevalence of aCL and anti-beta(2)GPI in black South African HIV positive patients, or those with syphilis, malaria, or hepatitis C virus is lower than reported for mixed race or white populations. aPT were the most prevalent aPL detected in these patient groups, except in patients with leprosy, for whom anti-beta(2)GPI was the most prevalent, and where the spectrum of aPL was similar to that seen in patients with SLE and APS.     

The prevalence of antibodies to anionic phospholipids in patients with the primary antiphospholipid syndrome, systemic lupus erythematosus and their relatives and spouses

OBJECTIVES: Antiphospholipid antibodies (aPL) have been associated with syndromes involving thrombosis, fetal loss and thrombocytopenia. Genetic and environmental conditions are among the factors attributed to the cause of autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The aim of this study was to determine whether these factors determine the prevalence of aPL. METHODS: Three groups of patients were tested for the presence of IgG, IgM and IgA anticardiolipin (aCL), antiphosphatidylinositol (aPI), antiphosphatidylglycerol (aPG) and antiphosphatidylserine (aPS) antibodies: (i) patients with primary APS (PAPS); (ii) patients with SLE and secondary APS; and (iii) patients with SLE without APS. First-degree relatives and spouses of patients with SLE/APS were also tested for circulating aPL. RESULTS: IgG aPL were particularly prevalent in patients with PAPS. IgG aPI and aCL were more prevalent in patients with PAPS than the IgM equivalents (P < 0.0001). Notably, none of the patients with PAPS had IgA aPL. A significantly higher number of relatives of patients with SLE/APS possessed IgG aPL than the normal controls. Except for aPG (P < 0.03), the prevalence of these antibodies in the relatives was not significantly different from patients with SLE/APS. The relatives also had significantly higher prevalence of IgG aPI, aPS and aCL antibodies than IgM aPL antibodies. In contrast, the prevalence of IgG aPL in the spouses was no different than in the healthy controls. CONCLUSIONS: Genetic factors, shared by patients and their relatives, seem to have some effect on the prevalence of aPL in the subjects studied, while environmental factors shared by spouses appear to have no influence.     

Antiphospholipid antibodies in HIV-positive patients

Antiphospholipid (aPL) antibodies classically have been associated with thrombotic phenomena and abortion in patients with autoimmune diseases. The objective of the present work was to evaluate the frequency of such antibodies in patients infected with HIV and study its association with the presence of clinical manifestations of antiphospholipid syndrome (APS). Using a transversal study, a population of patients diagnosed with HIV, identified through an enzyme-linked immunosorbent assay (ELISA) test and confirmed by Western blotting, aged above 17 years old, was investigated. Through a standard questionnaire, the presence of APS manifestations was investigated, as well as the frequency of rheumatic manifestations. Antibodies against beta2 glycoprotein I (anti-beta2 GPI) and anticardiolipin (aCL) IgA, IgG, and IgM were investigated by the ELISA method using commercial kits (QUANTA Lite, INOVA Diagnostics). Ninety patients were studied, 47 (52.2%) male and 43 (47.8%) female. Clinical manifestations of APS were detected in 12 patients (13.3%) of the studied population, whereas arthralgia was the most common rheumatic manifestation (38.9%). Of the 90 patients, 40 (44.4%) were reactive for at least one type of aPL antibody (aCL and/or anti-beta2 GPI). The frequency of aCL was 17.8%, from which 15 (16.7%) had aCL IgG, 3 (3.3%) IgM, and 1 (1.1%) IgA. The frequency of the anti-beta2 GPI antibody was 33.3%, from which 29 (32.2%) were positive for isotype IgA, 4 (4.4%) isotype IgM, and 1 (1.1%) isotype IgG. No association was observed between immunoreactivity for aPL antibodies in general or each isotype in particular and the presence of APS manifestation. In the present study, it was possible to observe a relatively high frequency of aPL antibodies, particularly for isotype IgA anti-beta2 GPI in HIV. However, there was no association to APS manifestations, suggesting that such antibodies had no etiopathogenic role in these complications in patients with such retroviral infection.     

Significance of persistent antiphospholipid antibodies in the elderly

OBJECTIVE: The prevalence of anticardiolipin antibodies (aCL) and of vascular diseases increases with age, and aCL may be associated with various diseases in the elderly. So the significance of aCL in the elderly remains difficult to determine. We sought to determine the significance of persistent antiphospholipid antibodies (aPL) in the elderly. METHODS: We retrospectively analyzed the files of 327 patients [149 patients with antiphospholipid syndrome (APS); 64 patients age >or= 65 yrs] with 2 positive aPL [lupus anticoagulant (LAC) and/or aCL]. RESULTS: The frequency of APS was 40.8% (n = 134) in our 263 young patients (< 65 yrs) and 23.4% (n = 15) in our 64 elderly patients (>or= 65 yrs). The clinical characteristics of patients with persistent aPL were the same in those under and over 65 years. LAC was positive in all but one elderly patient with APS, and occurred in this group more frequently than in the young patients (93.3% vs 44.6%; p < 0.006). The presence of LAC allowed to discriminate APS patients in our elderly population (93.3% in APS vs 48.9% in non-APS patients; p < 0.009). CONCLUSION: Interpretation of a positive determination of APL is difficult in the elderly; persistent LAC may be the most valuable biological marker of APS in the elderly.     

High prevalence of anti-prothrombin antibody in patients with deep vein thrombosis

The present study was designed to determine the prevalence of lupus anticoagulant (LA) antibody and several antibodies for antiphospholipid syndrome (APS) in patients with deep vein thrombosis (DVT)/pulmonary embolism (PE) (n = 48), cerebral thrombosis (CT, n = 30), systemic lupus erythematosus (SLE, n = 22), and idiopathic thrombocytopenic purpura (ITP, n = 30). The presence of antibodies was examined by using the respective ELISA kits. LA was positive in 38.6% of patients with DVT/PE, suggesting that LA is one of the most important risk factors in DVT/PE. The highest prevalence of anti-beta(2) glycoprotein I (beta(2)GPI) IgG was in CT and SLE, followed by DVT, and none in ITP and healthy volunteers (control, n = 40), suggesting that it is related to thrombosis, particularly arterial thrombosis. The highest prevalence of anti-prothrombin (aPT) IgG antibody was in DVT, followed by CT and SLE, and none in ITP and the control, suggesting that it is related to thrombosis, especially venous thrombosis. The highest prevalence of antiphospholipid (aPL) IgG was in DVT, CT, and SLE, but 0% in ITP and control. On the other hand, aPL IgM, anti-annexin V IgG, and anti-annexin V IgM were positive in patients both with and without thrombosis, suggesting that they are not related to thrombosis. Our results indicated that among the anti-phospholipid antibodies, LA is the most sensitive marker for APS while anti-beta(2)GPI IgG, aPT IgG, and aPL IgG are risk factors for thrombosis. In particular, aPT IgG is a significant marker for DVT/PE.     

Factor XIII in primary antiphospholipid syndrome

OBJECTIVE: To evaluate the clinical significance of factor XIII (FXIII) in primary antiphospholipid syndrome (APS). METHODS: A cross-sectional study including patients with primary APS (n =29), persistent carriers of idiopathic antiphospholipid antibodies (aPL) with no history of thrombosis (n = 14), thrombotic patients with inherited thrombophilia (n =24), healthy controls (n =28), and patients with mitral and aortic valve prosthesis (n =32, as controls for FXIII only). FXIII and fibrinogen were measured by functional assays: IgG anticardiolipin antibody (aCL), IgG anti-beta2-glycoprotein I (anti-beta2-GPI), and plasminogen activator inhibitor (PAI) by immunoassay; and paraoxonase activity by paranitrophenol formation. Intima-media thickness (IMT) of carotid arteries was determined by high resolution sonography. RESULTS: FXIII activity (FXIIIa) was highest in primary APS (p= 0.001), particularly in patients with multiple occlusions (n =12) versus those with single occlusion (158 +/- 45% vs 118 +/- 38%; p=0.02). In primary APS, FXIII positively correlated with PAI (p=0.003) and fibrinogen (p = 0.005). Similarly in the thrombotic control group, FXIIIa correlated with PAI (p =0.05) and fibrinogen (0.007). In primary APS, FXIIIa was related to the IMT of all carotid artery segments (p always < 0.01). In thrombotic controls FXIIIa correlated only to the IMT of the common carotid (p =0.01). In primary APS, FXIIIa was strongly associated with IgG aCL and IgG anti-beta2-GPI (p=0.005 for both). These associations were weaker in the aPL group (FXIIIa with IgG aCL, p= 0.02, with IgG anti-beta2-GPI, p=0.04). CONCLUSION: Enhanced FXIII activity may contribute to atherothrombosis in primary APS via increased fibrin/fibrinogen cross-linking. This pathway is not exclusive to primary APS, being present also in thrombotic controls, but the presence of IgG aPL may favor a higher degree of FXIIIa activation in the primary APS group.     

Relative value of different antiphospholipid antibodies detected in a department of internal medicine: retrospective study of 124 patients

PURPOSE: The value of antiphospholipid antibodies (aPL) detected in the sera of the patients of an Internal Medicine department is not univocal and is still much debated. To test the contribution of such new markers, we reviewed the records of patients having antiphospholipid antibodies detected between 1996 and 1997. METHODS: One hundred and twenty four patients, having at least one of these two aPL: lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or one of these two anti-proteins: anti-beta 2glycoprotéin I antibodies (anti-beta 2GPI) or anti-prothrombin antibodies (aPT), were studied. LA was detected by a PTT-LA technique and aCL, anti-beta 2GPI and aPT by ELISA-sandwich techniques. For each patient we recorded sex, age, personal and familial history of thrombosis, fetal losses and systemic disease, the reason of aPL detection, the final diagnosis, activated partial thromboplastin time (aPTT), platelets count and type of aPL. RESULTS: The population was composed of 77 women (62%) and 47 men (38%) with a mean age of 54 years [12-92 years]. A thrombocytopenia was strongly correlated to aCL presence (OR = 6.15 et p = 0.03). The reason of aPL detection was venous thrombosis, recurrent fetal losses, systemic disease, infectious disease or fortuitous discovery of a prolonged aPTT. The final diagnosis was a systemic disease in 57% of cases, an infectious disease in 14.5%, a thrombosis in 4.5% and a neoplasia in 3%. LA was detected in 54% of patients, aCL in 39.5%, anti-beta 2GPI in 23% and aPT in 31%. No relationship between the aPTT value and the type of aPL could be established. CONCLUSION: Our study shows that familial histories of venous thrombosis or systemic disease are useful to enhance antiphospholipid antibodies detection; that LA is mostly associated to systemic and infectious diseases; that aCL and anti-beta 2GPI are predominant in case of venous thrombosis and that thrombocytopenia has to enhance aCL detection and the discussion about a possible APS.     

Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study

Repeated thromboses are the most frequent clinical manifestation of antiphospholipid syndrome (APS) in the presence of antiphospholipid antibodies (aPL). The objective of this study was to observe the prevalence and localization of thrombosis, and to investigate the importance of aPL type and level for thrombosis-related events in patients diagnosed with APS. These are the first results of patients enrolled in Serbian National Cohort Study which comprises 256 patients: 162 with primary antiphospholipid syndrome (PAPS) and 94 with APS associated with systemic lupus erythematosus (SLE). aPL analysis included detection of aCL (IgG/IgM), β(2)GPI, and lupus anticoagulant. Thrombosis was diagnosed in 119 (46.5%) patients, with higher prevalence in PAPS compared with SLE patients (51.2% and 38.3%, respectively, p = 0.045). There was similar prevalence of arterial thrombosis in PAPS and SLE groups (34.6% and 34%, respectively, p = 0.932) although venous thrombosis was more frequent in PAPS (25.9% and 8.5%, respectively, p = 0.001). Thrombosis was observed in 92 (55.8%) patients who had more than one type of antibody (category I), in 13 (41.9%) patients with category IIa, in 19 (46.3%) patients with category IIb, and in 73 (44.2%) patients with category IIc (p = 0.10). The patients with thrombosis were older than those without thrombosis (49.8 and 39.8 years, respectively, p = 0.001). Overall, older age was a risk factor for thrombosis. The prevalence of venous thrombosis was higher in the PAPS group, but with lower frequency than in literature data. Any aPL type and level is a risk factor for thrombosis.     

Anti-beta2-glycoprotein I: prevalence, clinical correlations, and importance of persistent positivity in patients with antiphospholipid syndrome and systemic lupus erythematosus

OBJECTIVE: Antibodies to beta2-glycoprotein I (anti-beta2-GPI) are found in a large percentage of patients with primary or secondary antiphospholipid syndrome (APS). Our aim was to identify the prevalence and clinical correlation of these antibodies in patients with APS and systemic lupus erythematosus (SLE), in comparison to anticardiolipin (aCL) and the lupus anticoagulant (LAC). We investigated whether serial samples improve clinical utility. METHODS: Serum samples for anti-beta2-GPI (IgG, IgM, IgA), aCL (IgG, IgM, IgA), and LAC (by dilute Russell viper venom time; RVVT) were collected from 418 consecutive patients with SLE or APS between October 2002 and March 2003. Clinical and serologic data of these patients were analyzed. RESULTS: A total of 185 (44.5%) patients were positive for anti-beta2-GPI, 55.3% were positive for aCL, and 31.1% for LAC. Anti-beta2-GPI was more common in Caucasians than in African Americans (p = 0.098). IgM and IgA were the most frequent isotypes of anti-beta2-GPI. aCL and anti-beta2-GPI were highly associated (p < 0.0001 to p = 0.0177, depending on isotype). A positive association was found between the presence of the LAC by dilute RVVT and anti-beta2-GPI IgG (p < 0.0001), IgM (p < 0.0001), and IgA (p = 0.0002) antibodies. Persistent positivity increased the association of venous and arterial thrombosis with anti-beta2-GPI (IgG and IgM isotypes). Pregnancy loss, seizures, and migraines were not associated with anti-beta2-GPI. IgA anti-beta2-GPI was not significantly associated with any manifestation of APS. CONCLUSION: The prevalence of anti-beta2-GPI IgM and IgA was very high in our population. Measurement of anti-beta2-GPI IgG is clinically useful in identifying patients with SLE at higher risk for venous and arterial thrombosis. Persistent positivity increased the association of IgG anti-beta2-GPI with venous thrombosis and anti-beta2-GPI IgM with arterial thrombosis. IgA anti-beta2-GPI was not significantly associated with APS manifestations.     

Anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizures

The aim of this study was to examine whether the clinical features of antiphospholipid antibody syndrome are associated with anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with SLE. Seventy-six patients (71 females), who fulfilled 1982 ACR criteria for SLE, were prospectively studied for the clinical features of antiphospholipid antibody syndrome (APS), and their sera were analysed for the presence of IgG/IgM/IgA anti-cardiolipin antibodies (aCL) by an in-house ELISA and, in 65 of them, for the presence of IgG anti-beta2 glycoprotein I antibodies (anti-beta2 GPI) by a commercial kit. Thirty-nine (51%) patients were positive for aCL, all of which were positive for IgG aCL, either alone (79.6%) or along with IgM and/or IgA. Twenty-seven (69.3%) out of 39 aCL-positive and seven (26.9%) out of 26 aCL-negative sera were positive for IgG antibodies to beta2 GPI. There was a significant correlation (r = 0.66, P < 0.05) between the levels of aCL and anti-beta2 GPI antibodies. Forty-one patients had features of definite or suggestive APS. Thrombocytopenia, recurrent pregnancy loss and CNS manifestations (seizures eight, infarct one) were seen in 20, 13 and nine patients, respectively. Thrombosis of the peripheral vessels was seen in only one patient. Only the presence of seizures was significantly associated with the presence of aCL and anti-beta2 GPI antibodies (P < 0.05). The characteristic association of definite APS (recurrent pregnancy loss and arterial/venous thrombosis) was lacking.     

Real world experience with antiphospholipid antibody tests: how stable are results over time?

OBJECTIVE: To determine the stability and the degree of variation of antiphospholipid antibody (aPL) results over time in a large cohort of well evaluated aPL positive patients; and to analyse factors contributing to aPL variation and the validity of aPL in a real world setting in which aPL tests are done in multiple laboratories. METHODS: The clinical characteristics, drug treatment, and 1652 data points for lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (anti-beta2GPI) were examined in 204 aPL positive patients; 81 of these met the Sapporo criteria for antiphospholipid syndrome (APS) and 123 were asymptomatic bearers of aPL. RESULTS: 87% of initially positive LA results, 88% of initially negative to low positive aCL results, 75% of initially moderate to high positive aCL results, 96% of initially negative to low positive anti-beta2GPI results, and 76% of initially moderate to high positive anti-beta2GPI results subsequently remained in the same range regardless of the laboratory performing the test. Aspirin, warfarin, and hydroxychloroquine use did not differ among patients whose aCL titres significantly decreased or increased or remained stable. On same day specimens, the consistency of aCL results among suppliers ranged from 64% to 88% and the correlation ranged from 0.5 to 0.8. Agreement was moderate for aCL IgG and aCL IgM; however, for aCL IgA agreement was marginal. CONCLUSIONS: aPL results remained stable for at least three quarters of subsequent tests, regardless of the laboratory performing the test; the small amount of variation that occurred did not appear to be caused by aspirin, warfarin, or hydroxychloroquine use.     

IgG anti-beta2-glycoprotein I antibodies in adult patients with systemic lupus erythematosus: prevalence and diagnostic value for the antiphospholipid syndrome

OBJECTIVE: To investigate the prevalence of serum anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies and other antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). To study their diagnostic value for the antiphospholipid syndrome (APS). METHODS: Anti-beta2-GPI and IgG anticardiolipin (aCL) were determined in sera from 102 consecutive patients with SLE using ELISA. Serum and plasma tests were also done for lupus anticoagulant (LAC), syphilis, and antibodies to dsDNA. Clinical and laboratory features of APS were observed. RESULTS: Prevalences were 23.5% for aCL and 18.6% for anti-beta2-GPI. Correlations between the presence of aCL and anti-beta2-GPI and between their titers were statistically significant (p<0.0001). No associations were found between anti-beta2-GPI and disease activity criteria (SLEDAI, ECLAM, dsDNA). Anti-beta2-GPI were significantly associated with LAC (p = 0.005), APS (p = 0.005), and a high aCL titer (aCL > 5 SD; p< or =0.001). LAC was the best diagnostic criterion for APS. CONCLUSION: These data suggest that determination of anti-beta2-GPI in addition to aCL and LAC is unlikely to improve the diagnosis of APS in patients with SLE.     

Lupus anticoagulant: a marker for stroke and venous thrombosis in primary Sj?gren’s syndrome

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sj?gren’s syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American–European criteria) and 89 age–gender–ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (aβ2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney’s criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16?% patients and 5.6?% controls (p?=?0.035). LA was the most common aPL in patients (9?%), followed by aβ2GPI (5?%) and aCL (4?%). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls (p?=?0.061). Mean age at time of stroke was 35?years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney’s criteria) and were positive exclusively for LA. Comparison of patients with (n?=?16) and without (n?=?84) aPL revealed similar mean age, female predominance, and ethnicity (p?>?=0.387). Frequencies of livedo reticularis (25 vs. 4.8?%, p?=?0.021), stroke (12.5 vs. 0?%, p?=?0.024), and DVT (18.8 vs. 1.2?%, p?=?0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL (p?≥?0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.     

Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases

OBJECTIVE: Antiphospholipid (aPL) antibodies are present in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody syndrome (APS) and are associated with recurrent thromboses, thrombocytopenia, and pregnancy losses. The presence of aPL antibodies is routinely tested using a standardized ELISA that utilizes cardiolipin as antigen (aCL ELISA). This test, although sensitive, is frequently positive in patients with nonrelated autoimmune disorders and some infectious diseases, making the test less specific. Thus there is a need for more specific tests for aCL with equivalent sensitivity to the standard assay. We evaluated the diagnostic utility of a new aPL antibody test kit with a unique phospholipid mixture designed to be more specific than the standard anticardiolipin ELISA. METHODS: aPL antibodies (IgG, IgM) were measured by both a standard ELISA and a new ELISA kit (APhL ELISA Kit, Louisville APL Diagnostics, Inc., Louisville, KY, USA) in the baseline serum from patients enrolled in a 5 year inception cohort, prospective study of early rheumatoid diseases: rheumatoid arthritis (N = 70), SLE (70), scleroderma (45), inflammatory myositis (36), and early undifferentiated connective tissue disease (CTD) (165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjogren's syndrome (44) was also defined. Serum from 200 blood donors (BD) served as controls. Patients with known APS (33) and antinuclear cytoplasmic antibody positive renal vasculitis (52) were also studied. Laboratory personnel were blinded to sample diagnostic group. RESULTS: The kit was 90.9% sensitive for detecting APS. Seven patients missed by the kit all had standard aCL values < 40 PL units. Assuming controls do not have APS, the kit was 99.5% specific vs 96.0% for the standard assay. For the patients with CTD, the kit never detected a patient that was not also detected by the standard aCL assay. CONCLUSION: The APhL ELISA Kit appears to be more specific than the standard aCL ELISA without adding potential false positive results. The new test may be useful for followup study for patients found to be aCL positive by standard assays to increase specificity for aCL screening.     

Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome?

OBJECTIVE--Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS--A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with and without features of antiphospholipid syndrome (APS). Antiphospholipid antibody profile was subsequently evaluated in the aPL positive patients with and without aPL-related events, thus excluding the patients with complications of APS possibly due to factors other than aPL. RESULTS--LA showed a strong association with thrombosis and livedo reticularis, and IgG aCL with thrombosis and neurological disorders, while no clinical features were associated with IgM aCL. A considerable number of aPL positive patients with no aPL-related manifestations was also observed, suggesting the low specificity of aPL assays (54.4%). When studying the 60 aPL positive patients, LA was specific (91.3%) for the diagnosis of aPL-related thrombosis, whereas aCL were not specific, although IgG aCL mean levels were higher in patients with arterial thrombosis than in those without APS features. CONCLUSIONS--LA but not aCL positivity is a specific tool for the diagnosis of thrombotic complications due to aPL in SLE.     

Influence of hypergammaglobulinemia on antiphospholipid antibodies titres

PURPOSE: Antiphospholipid antibodies (aPL), anticardiolipin antibodies (aCL) or lupus anticoagulant (LA), are indispensable for the diagnosis of antiphospholipid syndrome (APS). However, antiphospholipid assays can generate false positive results. MATERIALS: We have studied the influence of hypergammaglobulinemia (HG) on aPL antibodies titers in 232 patients twice as positive for aPL antibodies. RESULTS: Out of 232 patients, 93 have an APS (76 primary APS, 17 secondary APS). Thrombosis occurred 138 times in APS patients. Of 139 patients without APS, 95 have an auto-immune disease, 28 have an isolated prolonged KCT and 16 an evolutive neoplasia. LA seems to be the best marker of APS. On the other hand aCL IgG and M, anti-beta2-GP1 IgM titers are significantly higher in patients without APS but with HG. CONCLUSION: Those results suggest that biological APS diagnosis should be carefully performed in patients with HG. In this case, other additional risk factors must be considered for the etiological diagnosis of thrombosis.     

Antiphospholipid antibodies in thromboangiitis obliterans

Thromboangiitis obliterans (TAO) and antiphospholipid syndrome (APS) share the clinical characteristics of arterial thrombosis and recurrent thrombophlebitis. Although the association of anticardiolipin antibodies (aCLa) and TAO has been previously recognized, the prevalence and the clinical impact of this association remains unclear. aCLa were measured by double ELISA in patients with TAO (n = 47), premature atherosclerosis (pASO) (n=48) and otherwise healthy individuals (n = 48). Antibody status was then compared to clinical presentation and outcomes in patients meeting the diagnostic criteria for TAO. The prevalence of aCLa was significantly higher in patients with TAO (36%) compared to either pASO (8%; p = 0.01) or healthy individuals (2%; p < 0.001). Patients with TAO and a high antibody titer tended to be younger and suffer a significantly higher rate of major amputations compared to those without the antibody (100% versus 17%; p = 0.003). Clinical features of TAO not significantly altered by the presence of aCLa included upper limb involvement, digital necrosis, superficial thrombophlebitis (or deep venous thrombosis). Protein C, protein S, and anti-thrombin III were normal in all individuals. TAO is associated with an increased prevalence of aCLa. The presence of a high antibody titer in these patients is associated with increased morbidity, including major limb amputation. In patients meeting the diagnostic criteria for TAO, screening for aCLa should be considered. Although attractive, the efficacy of chronic anticoagulation in this setting remains to be proven.     

Prevalence of the antiphospholipid syndrome in primary systemic vasculitis

BACKGROUND: The antiphospholipid (APS or Hughes') syndrome, anticardiolipin antibodies (aCL), and the lupus anticoagulant (LA) are associated with systemic lupus erythematosus, malignancy, infection, and drugs. It has been described in patients with primary systemic vasculitis (PSV). OBJECTIVE: To determine the prevalence of APS in patients with PSV attending a vasculitis clinic and the prevalence of patients with positive aCL and/or the LA who do not fulfil the classification criteria for APS. METHODS: All case notes of patients attending the vasculitis clinic over a 12 month period were reviewed. Outpatients and inpatients were both included and were assessed for features of the APS and presence of aPL. Patients with positive aCL or LA tests were classified according to the significance of these results. RESULTS: Of 144 patients with PSV, 25 had positive aCL or LA on at least one occasion, representing a point prevalence of 17%. Of these, nine had definite APS (classified by the Sapporo criteria) and a further four patients had clinical and serological features of APS, although insufficient to satisfy the Sapporo criteria. Twelve had only positive aPL. CONCLUSION: The antiphospholipid syndrome, aCL, and the LA may occur in association with PSV.