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Geographic and ethnic studies of aPL and APS suggest that IgG aCL prevalence may be lower among Afro-Caribbean (Jamaican) SLE patients, who interestingly have a high prevalence of IgA aCL. It is not clear whether this is generalizable to other SLE populations that have African ancestry. Further multi-ethnic studies that are internally controlled for laboratory methods and SLE disease activity would be useful in confirming these reports, and exploring their clinical significance.

APS/Hughes syndrome is an increasingly diagnosed condition. This chapter emphasizes the need for clinicians to consider the full range of differential diagnoses for each clinical state, so that the correct diagnosis is reached in an individual patient.

The first aCL test was developed in 1983 and subsequently standardized. Although in the last 6 to 7 years new and more specific tests have become available, the aCL ELISA and the LA tests are still the first choice to be used in diagnosis of APS. While there is now doubt that the aCL test is useful in the diagnosis of APS, limitations of the assay have caused uncertainty and misinterpretation of the value of the test. Utilization of validated ELISA kits with well-tested calibrators and an in-house standard may enable more reproducible measurements. Reporting results semi-quantitatively preserves the clinical use of the test without the misinterpretation of a quantitative result that may lack precision, The development of newer tests, such as the β-GPI ELISA and the APhL® ELISA Kit utilizing the phospholipid mixture, gives promise to a more specific and reliable diagnosis of APS while retaining good sensitivity. Other tests such as ELISA for prothrombin antibodies and annexin V antibodies are still under development and will require standardization and extensive evaluation.

Increased TF expression may contribute to thrombosis in patients with APS. This effect might ultimately depend on antibody engagement of PL binding proteins on the monocyte and the EC surface, leading to signal transduction and altered cell activity. Understanding the intracellular mechanism(s) of aPL mediated TF activation may help to establish new therapeutic approaches to revert the prothrombotic state observed in APS patients.

Because β-GPI was found to be a major antigen for aPL, many studies have been focused on the physiological role of β-GPI, on mechanism of thrombosis induced by anti-β-GPI antibody, and on clinical significance of this autoantibody. Physiological roles of β-GPI have been reported, although “true” property in human has yet to be determined. Several epitopes for anti-β-GPI antibodies are known, however, all of the anti-β-GPI antibodies may not be pathogenic and anti-β-GPI antibodies are heterogeneous. What we learn from these clinical reports would be as follows. First, the standardization of the assay system for aPL is urgent. Second, measurement of aPL using multiple methods is favored in order to establish better assay for diagnosis and/or for prediction of disease activity. Last, more prospective, multi-center studies will be needed after standardization of the assay systems.

Recently, pathogenic roles of anti-β-GPI antibodies have been reported in the fields of coagulation and fibrinolysis, atherosclerosis, or signal transduction and cell activation. These findings may contribute to better and specific therapies for patients with APS.

It has been demonstrated that the interaction between aPL and anionic phospholipids is mediated by plasma proteins, one of them identified as prothrombin. Antiprothrombin antibodies are frequently found in patients with aPL but the immunological characteristics and mechanisms of action are not completely understood. As thrombotic mechanisms are multifactorial and complex, further investigations are required to define the role of aPT in the pathogenesis of thrombosis. Knowledge of the behavior of specific aPL would aid in defining specific thrombogenic pathways and improved management of patients with APS. However, in order to accomplish this, standardization of the methods for the detection of these antibodies is mandatory.

Certain autoantibodies not detected in standard aCL and LA assays may be associated with clinical manifestations of APS. These antibodies are not included in the current serological criteria for the classification of definite APS, although these criteria are likely to be expanded in the future. Autoantibodies to β-GPI and prothrombin, detected in protein-based ELISAs, are likely candidates for consideration. At the present time antibodies detected in ELISAs using anionic phospholipids other than cardiolipin are of possible interest, however, evidence for the clinical utility of such assays is weak. Future studies elucidating the specificity of these antibodies and inter-laboratory efforts toward assay standardization are needed. Antibodies detected in anti-phosphatidylethanolamine assays may be associated with clinical features of APS and may directly contribute to a prothrombotic state.

In conclusion, certain patients with clinical features of APS may have 1 or more of the autoantibodies discussed above, in the absence of aCL or LA. While these patients do not meet current classification criteria for definite APS, conceptually they may be included in a broader clinical view of autoantibody-mediated thrombosis and pregnancy loss.

PAPS has emerged as an important disease entity. Depending on the organ systems involved, it can produce a highly variable clinical picture, with severity ranging from mild asymptomatic disease (often undiagnosed) to major life-threatening events. It may be regarded as the pure form of a condition which is also frequently seen in the context of other autoimmune diseases. In particular it is intricately linked to APS seen in the context of SLE; and these two variants of the condition appear to behave in a similar fashion. Defining PAPS provides us with the opportunity to study the disease in the absence of other co-morbid conditions such as SLE. Advances in our understanding of the pathogenesis of PAPS should facilitate the development of improved treatment and outlook for patients with all forms of the APS.

The first aCL test was developed in 1983 and subsequently standardized. Although in the last 6 to 7 years new and more specific tests have become available, the aCL ELISA and the LA tests are still the first choice to be used in diagnosis of APS. While there is now doubt that the aCL test is useful in the diagnosis of APS, limitations of the assay have caused uncertainty and misinterpretation of the value of the test. Utilization of validated ELISA kits with well-tested calibrators and an in-house standard may enable more reproducible measurements. Reporting results semi-quantitatively preserves the clinical use of the test without the misinterpretation of a quantitative result that may lack precision, The development of newer tests, such as the β-GPI ELISA and the APhL® ELISA Kit utilizing the phospholipid mixture, gives promise to a more specific and reliable diagnosis of APS while retaining good sensitivity. Other tests such as ELISA for prothrombin antibodies and annexin V antibodies are still under development and will require standardization and extensive evaluation.

The first aCL test was developed in 1983 and subsequently standardized. Although in the last 6 to 7 years new and more specific tests have become available, the aCL ELISA and the LA tests are still the first choice to be used in diagnosis of APS. While there is now doubt that the aCL test is useful in the diagnosis of APS, limitations of the assay have caused uncertainty and misinterpretation of the value of the test. Utilization of validated ELISA kits with well-tested calibrators and an in-house standard may enable more reproducible measurements. Reporting results semi-quantitatively preserves the clinical use of the test without the misinterpretation of a quantitative result that may lack precision, The development of newer tests, such as the β-GPI ELISA and the APhL® ELISA Kit utilizing the phospholipid mixture, gives promise to a more specific and reliable diagnosis of APS while retaining good sensitivity. Other tests such as ELISA for prothrombin antibodies and annexin V antibodies are still under development and will require standardization and extensive evaluation.