From the Guidelines
Ana testing with reflex to titer and cascade components is essential for diagnosing autoimmune diseases, particularly when interpreting results in the context of disease activity and immune system involvement. When evaluating patients with suspected autoimmune diseases, a comprehensive approach to ana testing is crucial, as highlighted by the international recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies 1. This approach typically involves an initial ana screening test, followed by reflex testing to determine the specific titer and identify specific autoantibodies present, as well as measuring complement components such as C3 and C4 to assess immune system activity. Key considerations in ana testing include:
- The titer level, which can correlate with disease activity, with higher titers (1:160 or greater) suggesting active autoimmune disease
- The presence of specific autoantibodies, which can help diagnose conditions like systemic lupus erythematosus (SLE), Sjögren's syndrome, and mixed connective tissue disease
- Complement levels, which are often decreased during active disease as they are consumed in the inflammatory process The importance of dedicated training for clinicians, technicians, and industry professionals in interpreting ana test results and understanding the significance of titers and patterns among different populations is also emphasized 1. In clinical practice, a reflex testing strategy for ana with titer and cascade components can provide valuable diagnostic information, enabling clinicians to make more accurate diagnoses and monitor autoimmune conditions effectively.
From the Research
Ana with Reflex to Titer and Cascade Components
- The diagnosis of autoimmune hemolytic anemia (AIHA) can be made with a stepwise approach that aims to identify laboratory and clinical evidence of hemolysis and then determine the immune nature of hemolysis with the direct anti-globulin test 2.
- The direct antiglobulin test can establish the diagnosis and subclassify the majority of autoimmune hemolytic anemias, and further testing to identify the driver of AIHA can have significant implications in overall management 3.
- An algorithmic approach to analyze the cause of anemia can accept as input three parameters from a CBC test: mean corpuscular volume, red cell distribution width, and reticulocyte count, and generate a probable etiology of the anemia, as well as automatically order reflex tests needed to confirm the diagnosis 4.
- Reflex tests can be modified depending on the policies of the institution using the algorithm, as different institutions may order different tests based on availability and costs 4.
- Advanced testing for rare nonimmune acquired hemolytic anemias or hereditary hemolytic anemias may be necessary if DAT testing is negative 3.
- Laboratory markers provide important information for the diagnosis and management of anemia, and specific treatments depend on the underlying anemia and etiology 5.
- Complement inhibitors have shown utility in stabilizing AIHA patients with acute severe hemolysis, and future prospects include the C1s inhibitor BIVV009 (sutimlimab) that is now entering phase 3 studies for CAD 2.