IgA Anticardiolipin Antibodies Research Articles

Obstetrical outcome and treatments in seronegative primary APS: data from European retrospective study

ObjectiveTo compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipidsyndrome (APS), to analyse factors associated with obstetrical outcome.Patients and methodsInclusion criteria were: (1) thrombotic and/or obstetrical APS...

Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review.

To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospholipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations. We searched PubMed and EMBASE using the key words APS, antiphospholipid antibodies, non-criteria, new assays, IgA anticardiolipin antibodies, lupus anticoagulant, anti-Domain I, IgA anti-β2-glycoprotein I antibodies, antiphosphatidylserine, anti-phosphatidylethanolamine, anti-phosphatidic acid, antiprothrombin, antiphosphatidylserine-prothtombin, anti-vimentin/cardiolipin complex and Annexin A5 resistance. Studies that met inclusion criteria to describe prevalence of non-criteria aPLs in APS patients (n > 10), disease and healthy control subjects were systematically examined. We selected 16 retrospective studies of 1404 APS patients, 1839 disease control and 797 healthy controls. The highest prevalence of non-criteria aPLs in the largest number of patients with APS was found in IgA anti-β2GPI studies (129/229, 56.3%), AnxA5R (87/163, 53.4%) and IgG anti-Domain I (241/548, 44.0%). Our finding of a significantly high prevalence of all non-criteria aPLs studied in patients with APS compared with controls was tempered by wide variation in sample size, retrospective collection, assay methodology and different determination of positivity. Therefore, prospective studies of sufficient size and appropriate methodology are required to evaluate the significance of these assays and their utility in the management of patients with APS.

Increased serum levels of soluble vascular endothelial-cadherin in patients with systemic vasculitis

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis (SV) in childhood characterized by an inflammatory reaction directed at vessels. Endothelial damage and perivascular leukocyte infiltrates are vital in the development of HSP. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule, which plays critical roles in angiogenesis and endothelial integrity. Herein, we investigated the serum levels of soluble VE-cadherin (sVE-cadherin) in patients with HSP and other forms of SV. The serum levels of sVE-cadherin in 30 patients with HSP, together with patients with urticarial vasculitis, allergic vasculitis, Behcet disease, psoriasis vulgaris (PV) and atopic dermatitis (AD) and 26 health controls were measured by enzyme-linked immunosorbent assay. Serum levels of sVE-cadherin were significantly increased in patients with HSP in acute stage and patients with other forms of SV but not in patients with PV or AD. Moreover, Serum sVE-cadherin levels in HSP patients were correlated with the severity of this disease and serum concentrations of IgA anticardiolipin antibodies and vascular endothelial growth factor. Taken together, we show firstly that serum sVE-cadherin is abnormally increased in HSP patients. Increased serum levels of sVE-cadherin might be a novel biomarker for evaluating the severity of HSP and useful for identifying the presence of SV in inflammatory skin conditions.

Clinical Significance of IgA Anti-Cardiolipin and IgA Anti-β2Glycoprotein I Antibodies

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.

Elevated serum interleukin-33 levels in patients with Henoch-Schönlein purpura

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis and is known as an immunoglobulin (Ig) A related immune complex-mediated disease. However, the molecular mechanisms in the development of HSP are not yet fully understood. Herein, we investigated the serum levels of Interleukin (IL)-33 and soluble ST2 (sST2) in HSP patients and their association with disease severity and IgA autoantibodies production. The serum levels of IL-33 and sST2 were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in the serum of 33 patients with HSP and 22 controls. Serum levels of IgA anti-endothelial cell antibodies (AECA) and IgA anticardiolipin antibodies (ACA) in HSP patients were detected by double antigen sandwich ELISA. Our results indicated that serum levels of IL-33 but not sST2 were significantly elevated in patients with HSP in acute stage and restored to normal levels in convalescent stage. Moreover, serum IL-33 levels were correlated with the severity of HSP and serum concentrations of AECA-IgA and ACA-IgA. Taken together, we show firstly that serum IL-33 is abnormally elevated in HSP patients. IL-33 might be associated with the IgA autoantibodies production in the pathogenesis of HSP.

Anticardiolipin antibodies do not mediate macrovascular complications of type 2 diabetes

The relationship of anticardiolipin antibodies (ACA), markers of the antiphospholipid syndrome, with vascular complications of diabetes mellitus is polemic. This cross-sectional study assessed the frequency of IgG, IgM, and IgA ACA in type 2 diabetics with and without history of vascular events for the last 5 years, and in healthy controls. ACA were detected by enzyme immunoassay. A total of 73 type 2 diabetics (33 with history of vascular events) and 54 healthy controls were tested. Most diabetics were female (p = 0.003), and older than controls (p 0.09). ACA positivity rates were also similar when diabetics with and without history of vasculopathy were compared (p > 0.47). After adjusting for gender, age, hypertension, and smoking status, a weak but statistically insignificant association between IgM ACA and diabetics with vasculopathy was found (adjusted OR 2.7; 95% CI 0.2 - 34.2; p = 0.441). Overall, levels of IgG (r = 0.25; p = 0.005) and IgM (r = 0.23; p = 0.010) ACA were associated with increasing age. In short, the frequency of a positive ACA test in type 2 diabetics (with or without previous macrovasculopathy) was not significant as compared to healthy controls. There was no association of ACA with vascular events in patients with type 2 diabetes.

Non-cirrhotic Intrahepatic Portal Hypertension: Associated Gut Diseases and Prognostic Factors

Non-cirrhotic intrahepatic portal hypertension (NCIPH) is generally regarded to have a benign prognosis. We have studied a cohort followed-up at a tertiary referral center and postulate that gut-derived prothrombotic factors may contribute to the pathogenesis and prognosis of NCIPH. We retrospectively analyzed prognostic indicators in 34 NCIPH patients. We also searched for associated gut diseases. Transplant-free survival in NCIPH patients from first presentation with NCIPH at 1, 5, and 10 years was 94% (SE: 4.2%), 84% (6.6%), and 69% (9.8%), respectively. Decompensated liver disease occurred in 53% of patients. Three (9%) patients had ulcerative colitis while five of 31 (16%) tested had celiac disease and on Kaplan-Meier analysis, celiac disease predicted reduced transplant-free survival (p=0.018). On multivariable Cox regression analysis, independent predictors of reduced transplant-free survival were older age at first presentation with NCIPH, hepatic encephalopathy, and portal vein thrombosis. Prevalence of elevated initial serum IgA anticardiolipin antibody (CLPA) was significantly higher in NCIPH (36% of patients tested), compared to Budd-Chiari syndrome (6%) (p=0.032, Fisher's exact test) and celiac disease without concomitant liver disease (0%) (p=0.007). We have identified prognostic factors and report progression to liver failure in 53% of NCIPH patients followed-up at our center. Our data supports a role for intestinal disease in the pathogenesis of intrahepatic portal vein occlusion leading to NCIPH.

Development of Recombinant Human IgA for Anticardiolipin Antibodies Assay Standardization

Controls and calibrators in autoimmune assays are typically developed from patient sera. However, the use of sera is accompanied by a number of disadvantages, such as lack of monospecificity, lack of assay comparability, and supply limitations. Ideally, the control reagent would be an antigen-specific human monoclonal antibody preparation that is defined and pure, easy to produce without any supply limitations, and of defined isotype (IgG, IgM, or IgA). The generation of antigen-specific human monoclonal antibodies has been complicated, but recent advances in development of fully human antibodies by means of in vitro antibody gene library selection has opened a way for the isolation of human antibodies to virtually any antigen, including self-antigens. Such antibodies can be converted to any isotype by gene cloning. Here we developed a set of human monoclonal IgA antibodies specific for the cardiolipin-beta2-glycoprotein 1 complex, using the HuCAL technology. We evaluated the IgA variants of those antibodies for their use as standards in IgA anticardiolipin antibody assays and compared these reagents with serum controls. Such recombinant antibodies may ultimately replace patient sera as assay control and calibration reagents.

Antiphospholipid antibodies increase the risk of pregnancy-induced hypertension and adverse pregnancy outcomes

Antiphospholipid antibody (aPL) is associated with thromboembolism. There is scant evidence of a relationship between the aPL profile and serious adverse pregnancy outcome. The aim of this study was to assess whether aPL measurements during early pregnancy were useful in predicting a serious adverse pregnancy outcome. In this prospective study, we measured aPLs, including lupus anticoagulant (LA), IgG, IgM, IgA anticardiolipin antibody (aCL), IgG, IgM phosphatidylserine-dependent antiprothrombin antibody, and IgG kininogen-dependent antiphosphatidylethanolamine antibody (aPE) during the first trimester in a consecutive series of 1155 women. The 99th percentile cut-off values in each aPL were determined using samples from 105 women who did not exhibit any pregnancy morbidity. We assessed the predictive risk of a serious adverse pregnancy outcome adjusted for confounding factors. We found that IgG aCL was asssociated with developing pregnancy-induced hypertension (PIH) (odds ratio 11.4, 95% CI 2.7–48); IgG aPE with PIH (8.3, 2.4–29), severe PIH (20.4, 4.5–91), and premature delivery (PD) (12.7, 3.1–50); and LA with PD (11.0, 2.8–44) and low birth weight (8.0, 2.1–31). The combinations of IgG aPE plus IgG aCL (17.5, 4.7–66.7) or IgG aPE plus LA (22.2, 5.4–909) measurements predicted severe PIH with 30.8% sensitivity and 99.2% specificity. We conclude that aPL measurements during early pregnancy may be useful in predicting adverse pregnancy outcome.

An Unusual Inhibitor of Coagulation Tests in a Patient with Lymphoproliferative Disease

We report the complex coagulation profile in a 74 year old female with progressive CLL and IgM paraproteinaemia and discuss the possible implication of these results in such a clinical setting. A 74 year old female with CLL was investigated for progression to high grade lymphoma and abnormal liver profile. Blood count parameters measured on a Sysmex 2100 were: Hb 10.5 g/dL (12–15.2); WBC 9.5 × 109/L (3.6–9.2) with lymphocytosis; PLT 71 × 109/L (180–380). She had deranged liver function with cholestatic picture thought to be due to NHL. Liver enzymes (U/L) were: Alk Phos 718 (30–250); AST 83 (<40); GGT 502 (< 75); ALT 41. She had a monoclonal IgM Lambda type paraprotein (5g/L) She also had a raised IgM ACA >80.0 MPLU/mL (0–7). IgG and IgA ACAs were normal. She had no bleeding diatheses.Coagulation parameters measured on a Sysmex CA1500 using Dade-Behring reagents and mixing with normal plasma showed markedly prolonged prothrombin time (PT) (Innovin) of 92 sec with no correction with normal plasma. The APTT was also markedly prolonged using (Actin FS) of 76sec and less prolonged at 48sec using lupus anticoagulant sensitive agent (Actin FSL) with no correction on mixing with normal plasma. Fibrinogen (Clauss) and TCT were normal. Thrombotest INR 1.2 (<1.1). DRVVT ratio 1.93; with no platelet neutralisation (0%.) KCT test ratio 0.99 (0.9–1.2); KCT mix ratio 2.19. All extrinsic coagulation factor assays performed with Thromborel-S (human placenta thromboplastin) were essentially normal. Similarly, intrinsic factor assays were also normal or above the normal range but there was some degree of non-parallelism.The inhibitor in our patient did not satisfy the criteria for diagnosis of a lupus-type anticoagulant (LTA). Furthermore, the more prolonged APTT result with Actin FS rather than with the more LTA-sensitive reagent Actin FSL mitigates the presence of LTA. The findings of a normal Thrombotest result and normal Thromborel-S derived coagulation factor assays suggest that the prolongation of the rTP-derived PT and the prolonged APTTs were not due to deficiencies of vitamin K dependent coagulation factors.We have previously described the phenomenon of non-correctable inhibition of rTP-derived PTs associated with anti-cardiolipin antibodies (ACA) in patients with lymphoproliferative disease and also in one patient with IgM lambda paraproteinaemia. This case showed more complex coagulation results. It is possible that the combined presence of IgM ACA and IgM Lambda paraproteins in this patient may have resulted unusually aggressive activity directed against the limited number of phospholipids used for relipidation of rTPs. We believe that the finding of prolonged rTP-derived PT in the presence of a normal conventional thromboplastin-derived PT should be followed up by routine screening for the presence of unsuspected ACA or paraproteinaemia in patients with lymphoproliferative disease. Further investigations are required to elucidate the nature of the antibodies produced in these patients and to determine the extent to which their inhibitory effects may be the consequence of a laboratory epiphenomenon.

Increased transforming growth factor-beta (TGF-beta)-secreting T cells and IgA anti-cardiolipin antibody levels during acute stage of childhood Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis characterized by increased serum IgA and IgA-dominant immune complex deposition in lesions. The involvement of IgA implies a probable role for TGF-beta, a major factor in IgA production, in the pathogenesis of HSP. Among IgA antibodies, serum IgA anti-cardiolipin antibodies (aCL) have been found in many diseases, including vasculitis. In addition to the clinical presentations and laboratory parameters, we further investigated the roles of IgA aCL and TGF-beta in childhood HSP. Twenty-six Chinese children with the diagnosis of HSP were enrolled. Blood samples from these patients were collected at both acute and convalescent stages. Intracellular staining of lymphocytes was performed to enumerate type 1 (interferon-gamma-secreting), type 2 (IL-4-secreting), and type 3 (TGF-beta-secreting) helper T cells. Serum levels of TGF-beta were detected by ELISA. Serum IgA aCL of 21 of 26 patients at the acute stage, 11 of them at the convalescent stage, were measured by ELISA. The data showed that IgA aCL serum levels were significantly elevated in patients compared with healthy controls (P < 0.001), and those patients at the convalescent stage (P < 0.001). In addition, TGF-beta-secreting T cells were significantly elevated during the acute stage, and decreased at the convalescent stage. Although more studies are needed, the high prevalence of IgA aCL and increased TGF-beta-secreting T cells in children with acute HSP revealed some points which should permit a better understanding of the pathogenesis of HSP.

Immunoglobulin class and IgG subclass distribution of anticardiolipin antibodies in patients with systemic lupus erythematosus and associated disorders

The class and subclass distribution of an antibody response may give insight into the stimulating mechanism and likely effector functions. IgA, IgG and IgM anticardiolipin antibodies (aCL) were quantified in a consecutive series of 200 samples sent to an autoimmune serology laboratory to determine the relationships between aCL responses of each of these antibody classes and, in particular, whether there was any utility in the measurement of IgA aCL. Positive results for one of the three aCL isotypes were found in 105 samples (53%), and in 41 samples IgA aCL was detected (21%). However, amongst these unselected samples, little additional information was obtained by measurement of IgA aCL, which was found in conjunction with IgM or IgG aCL in all but five samples, and in these the isolated elevation of IgA aCL was only slight, and showed no disease specificity. The levels of each of the four IgG subclasses of aCL were measured in a subgroup of serum samples from 28 patients with autoimmune disease and from 29 patients with syphilis. Amongst the SLE patients IgG1 and IgG3 aCL were the predominant IgG subclasses, consistent with an antigen-driven, T cell-dependent antibody response. However, a subgroup of eight of the autoimmune subjects had predominant elevation of IgG2 aCL, possibly implying a role for T cell-independent antibody production to cardiolipin. Amongst the syphilis patients IgG1 and IgG3 aCL were also the predominant subclasses of aCL but IgG4 aCL were also detected in the majority of subjects, consistent with prolonged antigenic stimulation.

Antiphospholipid antibodies in Brazilian hepatitis C virus carriers

Hepatitis C, a worldwide viral infection, is an important health problem in Brazil. The virus causes chronic infection, provoking B lymphocyte dysfunction, as represented by cryoglobulinemia, non-organ-specific autoantibody production, and non-Hodgkin's lymphoma. The aim of this research was to screen for the presence of antiphospholipid autoantibodies in 109 Brazilian hepatitis C virus carriers without clinical history of antiphospholipid syndrome. Forty healthy individuals were used as the control group. IgA, IgG, and IgM antibodies against cardiolipin and ss2-glycoprotein I were measured with an enzyme-linked immunosorbent assay, using a cut-off point of either 20 UPL or 20 SBU. While 24 (22.0%) hepatitis C carriers had moderate titers of IgM anticardiolipin antibodies (median, 22.5 MPL; 95%CI: 21.5-25.4 MPL), only three carriers (<3%) had IgG anticardiolipin antibodies (median, 23 GPL; 95%CI: 20.5-25.5 GPL). Furthermore, IgA anticardiolipin antibodies were not detected in these individuals. Male gender and IgM anticardiolipin seropositivity were associated in the hepatitis C group (P = 0.0004). IgA anti-ss2-glycoprotein-I antibodies were detected in 29 of 109 (27.0%) hepatitis C carriers (median, 41 SAU; 95%CI: 52.7-103.9 SAU). Twenty patients (18.0%) had IgM anti-ss2-glycoprotein I antibodies (median, 27.6 SMU; 95%CI: 23.3-70.3 SMU), while two patients had IgG antibodies against this protein (titers, 33 and 78 SGU). Antiphospholipid antibodies were detected in only one healthy individual, who was seropositive for IgM anticardiolipin. We concluded that Brazilian individuals chronically infected with hepatitis C virus present a significant production of antiphospholipid antibodies, mainly IgA anti-ss2-glycoprotein I antibodies, which are not associated with clinical manifestations of antiphospholipid syndrome.

IgA anticardiolipin antibody is associated with the extent of daily-life ischaemia in patients with chronic coronary artery disease

Background:Circulating anticardiolipin antibodies (aCL) may cause endothelial dysfunction. We investigated whether aCL are related to platelet activation, thrombin generation and daily-life ischaemia in patients with chronic coronary artery disease (CAD).Methods:We...

Vasculitis from the dermatological point of view

In vasculitis, dermatologists generally examine two kinds of patient who present with small-vessel vasculitis as defined by the Chapel Hill Consensus Conference nomenclature, and idiopathic cutaneous polyarteritis nodosa (CPN). CPN is a vasculitis of small and medium-sized arteries within the skin that does not involve internal organs. When these patients visit my clinic, I characterize the cutaneous manifestations at initial presentation and assess the histopathological findings. In systemic antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, the characteristic cutaneous clinical pattern of microscopic polyangiitis is livedo reticularis, whereas Churg-Strauss syndrome presents as purpura and petechiae with paresthesias on the lower extremities. When a patient presents with nodules on the elbows with histological palisading granuloma, diagnosis of three ANCA-associated vasculitis including Wegener's granulomatosis should be considered. In immune-complex-mediated vasculitis, Henoch-Schönlein purpura (HSP) is characterized by palpable non-thrombocytopenic purpura on initial clinical presentation. These clinical cutaneous investigations in vasculitis patients may allow us to refine our earlier diagnostic strategies. On the other hand, histological examination in a cryoglobulinaemic vasculitis patient revealed microvascular thrombus and leucocytoclastic vasculitis in the dermis. From these findings, I speculated that the presence of thrombosis may be somehow related to the pathogenesis of the vasculitis process and investigated the association between vasculitis, especially immune-complex-mediated vasculitis, and antiphospholipid antibodies (Abs). Serum levels of IgA anticardiolipin antibody (aCL) are elevated in the initial active stage of adult HSP, suggesting that the IgA aCL may play some role in the onset of adult HSP. We also suggest that CPN could be dependently associated with the presence of anti-phosphatidylserine-prothrombin complex Abs.

Assessment of Anticardiolipin antibodies, Circulating Lupus anticoagulant, Protein C, Protein S, Antithrombin III &Activated Protein C Resistance and Their Relation to Thomboembolic and Other Clinical Manifestations in Behcet's Disease

Background: Venous and arterial thrombosis occurs in patients with Behcet’s disease and is associated with significant morbidity and mortality. Studies on a possible association between the occurrence of thrombosis and thrombophilia in patients with this disease have been controversial. The objective of this study was to assess the frequency and clinical relevance of anticardiolipin antibodies (aCL) & other thrombophilic factors and their relationship to thromboembolic & clinical manifestations in Behcet's disease (BD). Materials and methods: IgG, IgM and IgA anticardiolipin antibodies (aCL) isotypes, presence of circulating lupus anticoagulant(LAC), protein C, protein S, antithrombin III & activated protein C resistance were investigated in 25 patients with BD and 25 patients with various rheumatic diseases not known to be associated with venous or arterial thromboembolic phenomena served as controls. Twelve of the patients with BD (48%) had either deep vein thrombosis (8 patients), arterial thromboembolic phenomena (4 patients), or both (2 patients). Results: The IgA aCL elevated in14 (56%) patients with BD compared with one (4%) patient in the control group (P<0.01). IgG aCL levels were elevated in 13 (52%) patients with Behcet's disease (BD) compared with one (4%) patient in the control group(P<0.01).Also patients with BD do not have decreased protein S, or antithrombin III activity, activated protein C resistance, circulating lupus anticoagulant (LAC), or elevated LgM aCL. No significant differences were found between any variable in both groups. No association between elevated IgMaCL levels and venous or arterial thrombosis and no statistical correlation was found between any factor and clinical manifestations of the disease. Conclusion: A significant number of patients have elevated levels of IgA& IgG aCL but they are not associated with venous or arterial thrombosis. These results do not suggest a primary role for aCL in BD and do not support the role of coagulation abnormalities in the pathogenesis of thromboembolic complications of Behcet’s disease but suggest vascular inflammation as the main pathogenetic event in the vascular lesions in Behcet’s disease.

Assessment of Anticardiolipin antibodies, Circulating Lupus anticoagulant, Protein C, Protein S, Antithrombin III &amp;Activated Protein C Resistance and Their Relation to Thomboembolic and Other Clinical Manifestations in Behcet's Disease

Background: Venous and arterial thrombosis occurs in patients with Behcet’s disease and is associated with significant morbidity and mortality. Studies on a possible association between the occurrence of thrombosis and thrombophilia in patients with this disease have been controversial. The objective of this study was to assess the frequency and clinical relevance of anticardiolipin antibodies (aCL) & other thrombophilic factors and their relationship to thromboembolic & clinical manifestations in Behcet's disease (BD). Materials and methods: IgG, IgM and IgA anticardiolipin antibodies (aCL) isotypes, presence of circulating lupus anticoagulant(LAC), protein C, protein S, antithrombin III & activated protein C resistance were investigated in 25 patients with BD and 25 patients with various rheumatic diseases not known to be associated with venous or arterial thromboembolic phenomena served as controls. Twelve of the patients with BD (48%) had either deep vein thrombosis (8 patients), arterial thromboembolic phenomena (4 patients), or both (2 patients). Results: The IgA aCL elevated in14 (56%) patients with BD compared with one (4%) patient in the control group (P<0.01). IgG aCL levels were elevated in 13 (52%) patients with Behcet's disease (BD) compared with one (4%) patient in the control group(P<0.01).Also patients with BD do not have decreased protein S, or antithrombin III activity, activated protein C resistance, circulating lupus anticoagulant (LAC), or elevated LgM aCL. No significant differences were found between any variable in both groups. No association between elevated IgMaCL levels and venous or arterial thrombosis and no statistical correlation was found between any factor and clinical manifestations of the disease. Conclusion: A significant number of patients have elevated levels of IgA& IgG aCL but they are not associated with venous or arterial thrombosis. These results do not suggest a primary role for aCL in BD and do not support the role of coagulation abnormalities in the pathogenesis of thromboembolic complications of Behcet’s disease but suggest vascular inflammation as the main pathogenetic event in the vascular lesions in Behcet’s disease.

Antiphospholipid antibodies may be a new prognostic parameter in aggressive non‐Hodgkin's lymphoma

Patients with malignancies have an increased prevalence of antiphospholipid antibodies (APA). The aim of this study was to determine the prevalence of IgG, IgM, and IgA anticardiolipin antibodies (aCL) and anti-beta-2 glycoprotein I antibodies (anti-beta2-GPI) in patients with non-Hodgkin's lymphoma (NHL), and to investigate their clinical and prognostic significance. The study group included 86 patients with NHL. Enzyme-linked immunosorbent assay kits were used to measure the concentrations of aCL and anti-beta2-GPI, and coagulation tests, to measure lupus anticoagulant (LAC) activity. Blood was collected at diagnosis in all patients and at follow-up in 15. Median follow-up time was 1.9 yr. Elevated APA levels were found in 35 patients (41%) at diagnosis: one patient aCL IgG, five patients aCL IgM, five aCL IgA, one anti-beta2-GPI IgG, 14 anti-beta2-GPI IgM, and 19 anti-beta2-GPI IgA; LAC activity was found in three of 67 patients (4.5%). There was no significant correlation between elevated APA levels and patient's age or sex, disease stage or grade, bone marrow involvement, B symptoms, serum lactate dehydrogenase levels, serum beta2 microglobulin levels, International Prognostic Index (IPI) score, performance status, type of treatment, or response to treatment. There was a correlation between elevated APA and absence of extranodal disease (P = 0.045). A strong negative correlation was found between elevated APA at diagnosis and survival time. Two-year survival was 90 +/- 5% for patients without APA at diagnosis compared with 63 +/- 11% for patients with an elevated APA levels (P = 0.0025). APA added to the predictive value of IPI for event-free and overall survival. APA are elevated in 41% of NHL patients at diagnosis and are correlated with shortened survival. Their level may serve as an independent prognostic variable in aggressive NHL.

Celiac Disease Associated With Nodular Regenerative Hyperplasia, Pulmonary Abnormalities, and IgA Anticardiolipin Antibodies

The association of nodular regenerative hyperplasia with celiac disease is not as well established as it is with hepatopulmonary syndrome and portopulmonary hypertension. IgA anticardiolipin antibodies were reported recently in celiac patients with nodular regenerative hyperplasia. The subject of this study was the description of pulmonary abnormalities and IgA anticardiolipin antibodies in celiac patients with noncirrhotic portal hypertension. Five patients with portal hypertension were investigated to diagnose its etiology. Celiac disease was diagnosed by means of autoantibody reactivity and duodenal biopsies. Liver histology revealed nodular regenerative hyperplasia in four patients and suggested its presence in 1 case. Two cyanotic patients had severe hypoxemia with a confirmed diagnosis of hepatopulmonary syndrome. Another case exhibited features of hepatopulmonary syndrome with increased levels of arterial pulmonary pressure. The remaining 2 cases had slight abnormalities of arterial oxygenation. Three patients had reactivity to IgA anticardiolipin antibodies. The concomitance of celiac disease and nodular regenerative hyperplasia, two infrequent conditions, raises suspicion of there being a nonfortuitous coincidence. Pulmonary abnormalities, and especially hepatopulmonary syndrome, are described for the first time in association with celiac disease and nodular regenerative hyperplasia.

IgA Anticardiolipin Antibodies as a Risk Factor for Arterial and Venous Thrombotic Events.

Background: Many studies have concluded that the presence of anticardiolipin antibodies is associated with both venous and arterial thrombotic events. The role of IgA anticardiolipin has been studied previously with conflicting results. Some of this disparity is thought to be due in part to the lack of international standards in measuring these levels.Objective : To further evaluate the role of IgA anticardiolipin anitbody as a risk factor for thrombosis.Patients and Methods: We conducted a single institution retrospective review of all patients with elevated IgA anticardiolipin antibodies extracted from a database of 20,000 patients for whom IgA anticardiolipin had been measured.Results: One hundred forty-eight patients were identified with elevated IgA anticardiolipin antibodies as measured by semiquantitative indirect Elisa. Patients had a median age of 52.5; 52% were African American, 38% Caucasain and 9% of other ethnic background. Of these patients, 67 had associated arterial or venous thrombotic events: 15.9% were pulmonary embolisms, 47.5% were deep venous thromboses and 36.6% were arterial thrombotic events. Patients were further evaluated for other thrombotic risk factors including IgG and IgM anticardiolipin antibodies; lupus anticoagulant; pt 20210; activated protein C resistance/Factor V Leiden; hyperhomocysteinemia; antithrombin; protein C/protein S deficiency; active malignancy with or without concurrent chemotherapy; tamoxifen, oral contraceptive or hormone replacement therapy; catheter-related risk; pregnancy; myeloproliferative disorders and hyperviscosity syndromes; sickle cell disease; and surgery, trauma or immobilization within 6 weeks of the event. In 35.8% of evaluated patients with elevated IgA and thrombotic events, there was was no concommitant elevation of IgG or IgM anticardiolipin. In 33.3% of patients with thrombotic events, none of the other predetermined risk factors were present.Conclusion: IgA anticardiolipin may be an independent risk factor for development of venous and arterial thrombotic events. A large case-controlled or prospective, randomized trial with standardized measurement will likely be needed to further clarify this issue.