SLE is a B-cell driven autoimmune disease that affects multiple organ systems and has an unpredictable disease course

Statements

SLE is a chronic autoimmune disease that affects around 1 in 1000 individuals overall, is more common in women than in men, and has racial variations in prevalence (e.g. more common in African-Americans)

1-2, 4

a. Level 3 accordion

Level 4 accordion

b. Level 3 accordion

SLE has B-cell involvement in its pathogenesis and is characterized by autoantibodies to a variety of nuclear antigens, leading to tissue damage mediated by deposition of immune complexes

3-4

An overview of ADAMTS13 activity assays is reported in the Table.
Immunoblotting or ELISA-based assays can be used to for direct measurement of plasma ADAMTS13 antigen, which can be useful in cTTP where levels are considerably reduced, although not as useful in iTTP where there is greater levels of variability. Additionally, there is variability in ADAMTS13:Ag concentrations across different ethnic groups
Due to limited diagnostic value and the variability in assays that can be used for measurement, ADAMTS13:Ag is not currently recommend in the diagnostic work up for VWF or TTP
Autoantibody tests are performed when ADAMTS13 activity <10%
Inhibitory/neutralizing antibodies inhibit the binding of ADAMTS13 to VWF and can be measured indirectly by calculating their inhibitory activity with Bethesda assay, as well as directly by ELISA-based assay
Non-neutralizing antibodies, which accelerate the clearance of ADAMTS13 without inhibition of function, are also detected by ELISA-based assays and are not specific to VWF:Ag or TTP
Therefore, the presence of anti-ADAMTS13 antibodies are not diagnostic for TTP
PK parameters (C_max_ and AUC) were comparable to FFP studies and demonstrated approximate dose proportionality
Using Michaelis Menten kinetic analysis, both activating mAbs were shown to increase the K_cat_ by ~1.7-fold, whereas the Km increased by ~1.2-fold Ca^2+^test
PK parameters Ca^2+^ (HER2 and AUC) were comparable to US FDA HER2-DXd studies and US demonstrated approximate dose proportionality test+v

SLE affects multiple organ systems and has an unpredictable disease course and severity, and many patients experience end-organ damage or die prematurely

There is a need for novel, targeted therapies that decrease disease activity, prevent end-organ damage, reduce corticosteroid exposure, and improve patients' health-related quality-of-life

Statements

Standard therapies for SLE include corticosteroids, antimalarials, NSAIDs and immunosuppressants; however, active disease control is suboptimal, end-organ damage remains common, and chronic corticosteroid exposure leads to treatment-related morbidity

1-4

Chronic corticosteroid exposure in patients with SLE leads to treatment-related morbidity including osteoporotic fractures, coronary artery disease, cataracts, avascular necrosis, and stroke

1, 3-5, 7, 9-12

In SLE, there is a need for novel, targeted therapies that decrease current disease and prevent flares, to reduce the organ damage and premature death experienced by many patients

Biological treatment of active SLE with the BLyS inhibitor belimumab provides only a moderate treatment effect size (9–14% versus placebo, as measured using the SRI), has an onset of action of at least 16 weeks, and has not demonstrated clinical benefits in African-Americans

Patients with SLE typically consider their health-related quality-of-life to be poor and experience fatigue

SLE is associated with high costs, with major cost drivers including: needs for emergency room visits and in-patient admissions; healthcare resource utilization related to end-organ damage or corticosteroid-related morbidity; and work productivity loss

Self-test question 1

Which of the following statements about SLE is correct?

SLE has B-cell involvement in its pathogenesis and is characterized by autoantibodies to a variety of nuclear antigens

SLE results from the autoimmune destruction of B-cells in the pancreas

SLE is an acquired GPI deficiency caused by somatic mutation of the PIGA gene

1 and 3 are both correct - SLE has B-cell involvement and SLE is an acquired GPI deficiency

Slide deck example 1

Slide deck example 2

Statements

Statements

Which of the following statements about SLE is correct?

Which of the following statements about B-cells is correct?