Do antiphospholipid antibodies develop for a purpose?

There is a growing body of literature suggesting that antiphospholipid antibodies develop for a purpose, that they play several key roles in the innate immune response, and are only rendered pathologic in susceptible people under adverse intravascular conditions. This paper will review evidence that the autoantibodies associated with the antiphospholipid syndrome develop from natural autoantibodies for purposes that are beneficial to host defense, and are only rendered pathologic as a result of adverse intravascular events.

The prevalence and clinical significance of antiphospholipid antibodies in rheumatoid arthritis.

Published data were reviewed to evaluate the occurrence of antiphospholipid antibodies (aPL) in rheumatoid arthritis (RA) patients and to investigate their clinical relevance in this population. The mean prevalence was calculated at 28% and the median was 22%. Few studies have found a relationship between aPL antibodies and thrombosis, particularly in combination with other risk factors.

Combined oral contraceptives in women with systemic lupus erythematosus.

Background: Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus.

Methods: A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.

Computer-assisted pattern recognition of autoantibody results.

Immunoassay-based anti-nuclear antibody (ANA) screens are increasingly used in the initial evaluation of autoimmune disorders, but these tests offer no "pattern information" comparable to the information from indirect fluorescence assay-based screens. Thus, there is no indication of "next steps" when a positive result is obtained. To improve the utility of immunoassay-based ANA screening, we evaluated a new method that combines a multiplex immunoassay with a k nearest neighbor (kNN) algorithm for computer-assisted pattern recognition.

DHEA supplementation: the claims in perspective.

Deficiency of dehydroepiandrosterone (DHEA) is associated with lupus erythematosus, diabetes mellitus, Alzheimer disease, and some cancers, but we are not yet ready to conclude that prescribing supplemental DHEA is helpful in these or any other conditions. DHEA shows some promise in observational clinical studies and laboratory experiments, but we still need large-scale human studies to answer key questions. For now, we do not have enough evidence to recommend routine treatment with DHEA.

Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis.

Background: Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable.

Methods: We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.

The role of biomarkers in the assessment of lupus.

Although considered a prototypic autoimmune disease, the hallmark of systemic lupus erythematosus (SLE) is its heterogeneity. Accordingly, manifestations can vary widely from person to person, with the potential involvement of virtually any bodily organ. Furthermore, the genetic abnormalities underlying this condition are complicated, with diverse genetic polymorphisms described in different ethnic groups, strongly suggesting that the actual pathology underlying the immunologic disarray might not be the same for each patient.

The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial.

Background: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE).

Objective: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE.

Design: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002.

Emergence of targeted immune therapies for systemic lupus.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, characterised by flares of rampant inflammation that can threaten, in an unpredictable manner, almost any organ in the body. Current standard of care is largely empiric, involving the use of corticosteroids and toxic immune suppressive agents that are widely acknowledged to have unacceptable side effects for long-term use. Recently, there have been significant advances in understanding the nature of some fundamental immune imbalances underlying the complicated clinical manifestations of SLE.

Challenges in bringing the bench to bedside in drug development for SLE.

It is now widely accepted that the current standard of care for systemic lupus erythematosus (SLE) patients is inadequate. There has not been a new medication approved for this disease in thirty years. Attempts to develop and test new drugs have been ongoing since the mid-1990s, but have encountered formidable obstacles.

Defining response in systemic lupus erythematosus: a study by the Systemic Lupus International Collaborating Clinics group.

Objective: In a preliminary attempt to develop a drug responder index for patients with systemic lupus erythematosus (SLE), 2 validated disease activity instruments were studied for their responsiveness and compared to a physician visual analog scale (VAS) assessment of disease activity. We attempted to determine whether these validated instruments were useful components in characterizing response in the setting of a clinical trial.

Methods: Eighty paper patients were assessed using the British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Disease Activity Index (SLEDAI) and by physician's assessment of global activity.

Diagnosis of the antiphospholipid syndrome: how far to go?

The past decade has seen an evolution in the way that thrombophilic conditions are diagnosed and understood. This has largely evolved through the detection of single nucleotide polymorphisms in critical regulating proteins that are thought to confer significant structural-functional changes at key points in the coagulation cascade. The antiphospholipid syndrome (APS) is a complex hypercoagulable disorder that as yet defies the possibility of simple, predictive testing.

Genetics of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial or venous thrombosis or fetal loss and the presence of antiphospholipid antibodies (aPL). Genetic factors are thought to play a role in the susceptibility to APS. Similar to many other polygenic autoimmune diseases, human leukocyte antigen associations have been reported.

Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus.

Objective: To determine whether prasterone administration results in improvement or stabilization of systemic lupus erythematosus (SLE) disease activity and its symptoms.

Methods: Women with active SLE were treated with prasterone 200 mg/day plus standard SLE treatments or with placebo plus standard SLE treatments for up to 12 months in this randomized, double-blind investigation conducted at 27 centers. Standard SLE treatments included prednisone (/=6 weeks prior to enrollment and remain unchanged during protocol treatment.

IgG autoantibodies against beta2-glycoprotein I complexed with a lipid ligand derived from oxidized low-density lipoprotein are associated with arterial thrombosis in antiphospholipid syndrome.

We recently reported [J. Lipid Res. 42 (2001), 697; 43 (2002), 1486; 44 (2003), 716] that [beta2-glycoprotein I (beta2GPI) forms complexes with oxidized LDL (oxLDL) and autoantibodies against these complexes are present in patients with SLE and antiphospholipid syndrome (APS).

Anti-beta 2-glycoprotein I and antiphosphatidylserine antibodies are predictors of arterial thrombosis in patients with antiphospholipid syndrome.

The predictive value (PV) and association of 4 antiphospholipid antibodies with clinical manifestations of the antiphospholipid syndrome (APS) were evaluated in 90 patients with systemic lupus erythematosus (SLE) and 100 with APS. Patients with APS were classified into arterial thrombosis, venous thrombosis, and pregnancy morbidity subgroups. IgG, IgM, and IgA anticardiolipin (aCL), antiphosphatidylserine (aPS), anti-beta 2-glycoprotein I (anti-B2GPI), and antiprothrombin (aPT) antibodies were determined by enzyme-linked immunosorbent assay.

Antibodies directed to protein S in patients with systemic lupus erythematosus: prevalence and clinical significance.

Antibodies directed against protein S (anti-ProtS) may be involved in the development of thrombosis in patients with the antiphospholipid syndrome. We assessed the prevalence and clinical significance of anti-ProtS and evaluated their immunological characteristics in 184 patients with SLE and 99 healthy donors. All patients were tested for IgG anti-ProtS by an in-house ELISA.

The antiphospholipid syndrome and atherosclerosis: clue to pathogenesis.

Regulation of blood vessels is intrinsically tied to inflammatory signaling. Recent research suggests that chronic inflammation is associated with atherosclerosis risk. The antiphospholipid syndrome is a prototypic autoimmune disease.

Dehydroepiandrosterone, a sex steroid metabolite in development for systemic lupus erythematosus.

Deficiency of the weak androgen dehydroepiandrosterone (DHEA) and its sulfoconjugated metabolite DHEA-S has been associated with a number of serious illnesses, including lupus, diabetes, Alzheimer's disease and some cancers. Accordingly, supplementation with DHEA has been proposed for a variety of illnesses. Observational clinical studies and in vitro experiments have suggested that DHEA treatment might have a significant impact on immunological function, bone density, cognition, atherosclerotic disease, some malignancies, insulin resistance and obesity.