What antibodies are used to rule out amyloidosis?

Antibodies to Rule Out Amyloidosis

To rule out AL (light chain) amyloidosis, you must perform serum and urine immunofixation electrophoresis to detect monoclonal proteins, along with serum free light chain (FLC) assay with kappa/lambda ratio—these are not "antibodies" per se, but rather tests that detect abnormal immunoglobulin light chains that cause AL amyloidosis. 1

Critical Clarification: The Question Likely Refers to Immunoglobulin Testing, Not "Antibodies"

The term "antibodies" in this context is somewhat misleading. What you're actually looking for are:

• Monoclonal immunoglobulin proteins (the pathologic proteins causing AL amyloidosis)
• Immunohistochemistry antibodies (used on tissue to type amyloid deposits)

Laboratory Tests to Rule Out AL Amyloidosis

Serum Studies (Essential First Step)

• Serum protein electrophoresis (SPEP) with immunofixation to detect monoclonal proteins 1
• Serum free light chain (FLC) assay with kappa/lambda ratio:
  • Normal ratio: 0.26-1.65 (Binding Site method) or 0.31-1.56 (Siemens method) in patients with normal renal function 1
  • Abnormal ratio suggests AL amyloidosis 1
• Quantitative immunoglobulins (IgG, IgA, IgM) 1

Urine Studies

• 24-hour urine collection for protein electrophoresis and immunofixation 1
• This detects Bence Jones proteins (free light chains in urine) 1

Why This Matters for Diagnosis

• If serum/urine immunofixation and FLC ratio are NORMAL, AL amyloidosis is effectively ruled out 1, 2
• This is critical because the diagnostic algorithm for ATTR (transthyretin) cardiac amyloidosis using 99mTc-PYP scintigraphy requires negative monoclonal protein studies to avoid false positives 2
• Over 10% of patients with monoclonal gammopathy can have ATTR deposits, making this distinction essential 2

Immunohistochemistry Antibodies (For Tissue Typing After Biopsy)

Once amyloid is confirmed on tissue biopsy with Congo red staining, immunohistochemistry uses antibodies against specific amyloid proteins to determine the type: 1, 3, 4

• Anti-kappa light chain antibodies
• Anti-lambda light chain antibodies
• Anti-transthyretin (TTR) antibodies
• Anti-amyloid A antibodies

Important Limitations

• Immunohistochemistry has limited sensitivity and specificity due to variable quality of commercial antibodies 3, 4
• Mass spectrometry is the gold standard for amyloid typing (88% sensitivity, 96% specificity), superior to immunohistochemistry 5, 3, 4

Diagnostic Algorithm to Rule Out Amyloidosis

Step 1: Clinical Suspicion

• Unexplained heart failure with LV wall thickness >12 mm, low voltage on ECG despite thick walls, or restrictive cardiomyopathy 1

Step 2: Screen for AL Amyloidosis (Must Be Done First)

• Serum immunofixation + FLC ratio 1, 2
• Urine immunofixation 1
• If both negative, AL amyloidosis is ruled out 2

Step 3: If Monoclonal Protein Studies Are Negative

• Proceed with 99mTc-PYP scintigraphy to diagnose ATTR cardiac amyloidosis (Grade 2-3 uptake with heart-to-contralateral lung ratio >1.5 at 1 hour) 2

Step 4: If Monoclonal Protein Studies Are Positive

• Do NOT rely on PYP scan alone—requires endomyocardial biopsy with mass spectrometry for definitive typing 2
• Refer to specialized amyloid center 2

Critical Pitfalls to Avoid

• Never skip monoclonal protein screening before interpreting a PYP scan—false positives occur when monoclonal proteins are present 2
• Do not use the term "antibodies to rule out amyloidosis" literally—you're testing for abnormal immunoglobulins (the disease-causing proteins), not therapeutic or diagnostic antibodies 1
• Immunohistochemistry alone is insufficient for amyloid typing due to antibody limitations; mass spectrometry is preferred 5, 3, 4
• Cardiac biomarkers (NT-proBNP ≥332 ng/L has >99% sensitivity for cardiac AL involvement) are for staging, not ruling out disease 1