Monoclonal gammopathies and immunofixation

6 DOH Abu Dhabi (HAAD) lab licensing practice questions on Monoclonal gammopathies and immunofixation, part of Immunology and Serology. The first 6 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   A 64-year-old man with IgG kappa myeloma has been on lenalidomide maintenance since an autologous stem cell transplant 2 years ago. Free light chain reference intervals: kappa 3.3-19.4 mg/L, lambda 5.7-26.3 mg/L, ratio 0.26-1.65. A year ago: M-protein 2 g/L, free kappa 18 mg/L, free lambda 12 mg/L, creatinine 88 µmol/L (1.0 mg/dL). Today: M-protein still 2 g/L, free kappa 640 mg/L, free lambda 8 mg/L, creatinine 168 µmol/L (1.9 mg/dL), hemoglobin 98 g/L (9.8 g/dL), down from 128 g/L, and urine immunofixation shows free kappa. The most likely explanation is:

   1. ARelapse as free light chain escape
   2. BReduced renal clearance of light chains
   3. COligoclonal immune recovery after transplant
   4. DPolyclonal B-cell activation by infection

   Show answerHide answer

   Answer: A · Relapse as free light chain escape

   The kappa/lambda ratio has risen from 1.5 to 80 (640 ÷ 8), with lambda suppressed, while the intact IgG M-protein has not changed: a clone has emerged that secretes only free kappa chains. This light chain escape is a recognized form of relapse, and the rising creatinine, falling hemoglobin and free kappa in the urine show that it is already causing damage. Reduced kidney clearance raises kappa and lambda together and keeps the ratio close to normal, and polyclonal activation also raises both. Oligoclonal bands after transplant appear on immunofixation and do not produce a ratio of 80. This is why myeloma is monitored with serum free light chains as well as the M-protein.

   • B: Kidney impairment raises both light chains, so the ratio stays near normal.
   • C: Oligoclonal bands show on immunofixation and do not give a kappa/lambda ratio of 80.
   • D: Polyclonal activation raises kappa and lambda together.

2. Question 2 · Medium

   Serum free light chains: kappa 168 mg/L (reference 3.3-19.4), lambda 11.2 mg/L (5.7-26.3); ratio reference 0.26-1.65. The kappa/lambda ratio and its meaning are:

   1. A157; abnormal, consistent with a kappa clone
   2. B0.07; abnormal, consistent with a lambda clone
   3. C1.50; within the reference interval
   4. D15.0; abnormal, consistent with a kappa clone

   Show answerHide answer

   Answer: D · 15.0; abnormal, consistent with a kappa clone

   The ratio is kappa divided by lambda: 168 / 11.2 = 15.0, far above the upper limit of 1.65. A raised ratio shows an excess of one light-chain type, here kappa, from a clonal plasma cell or B-cell population, while lambda stays normal. Dividing lambda by kappa gives 0.07 and the wrong clone, a decimal slip gives 1.50, and subtracting gives the difference (dFLC, 156.8 mg/L), which is a separate measure. The ratio is interpreted together with SPEP and immunofixation.

   • A: 157 is the difference between kappa and lambda, not the ratio.
   • B: 0.07 is lambda divided by kappa, the inverted ratio.
   • C: 1.50 comes from misplacing the decimal point.

3. Question 3 · Medium

   Serum immunofixation shows a discrete band in the lambda lane, with no matching band in the IgG, IgA or IgM lanes. What is the best next step?

   1. ARepeat SPEP at a higher voltage
   2. BReport free lambda light chains without further tests
   3. CRepeat immunofixation with anti-IgD and anti-IgE
   4. DReport an IgM lambda M-protein

   Show answerHide answer

   Answer: C · Repeat immunofixation with anti-IgD and anti-IgE

   A light-chain band without a matching heavy-chain band is either free lambda light chain or an M-protein whose heavy chain was not tested, usually IgD and, very rarely, IgE. Immunofixation with anti-IgD and anti-IgE separates these; IgD myeloma is mostly of lambda type. Only when both are negative is the band reported as free lambda light chains, which a serum free light chain assay can then quantify.

   • A: SPEP cannot type the band, and changing the voltage does not help.
   • B: IgD and IgE must be excluded before the band is called free light chains.
   • D: An IgM M-protein would show a band in the IgM lane.

4. Question 4 · Hard

   A 62-year-old has nephrotic-range proteinuria and a thickened heart wall on echocardiography; creatinine is 88 µmol/L (1.0 mg/dL). SPEP shows no M-spike and serum immunofixation is negative. Free kappa 9.0 mg/L, free lambda 92 mg/L; ratio reference 0.26-1.65. What is the best interpretation?

   1. ALambda clone; AL amyloidosis should be suspected
   2. BKappa clone with suppression of lambda
   3. CNo clone, since serum immunofixation is negative
   4. DPolyclonal rise from kidney damage; no clone

   Show answerHide answer

   Answer: A · Lambda clone; AL amyloidosis should be suspected

   The ratio is 9.0 / 92 = 0.10, well below 0.26, showing an excess of monoclonal lambda light chains. In AL amyloidosis the clone is often small, so SPEP and serum IFE can be negative while the free light chain assay detects it, and lambda clones predominate. Nephrotic syndrome and cardiac thickening are typical organ involvement, and tissue biopsy with amyloid typing confirms the diagnosis. Kidney impairment raises both light chains and shifts the ratio upward, not down to 0.10.

   • B: Kappa is normal and lambda is high, so the excess chain is lambda.
   • C: The free light chain assay is more sensitive than serum immunofixation for small clones.
   • D: Reduced kidney clearance raises both chains and nudges the ratio up, and her creatinine is normal.

5. Question 5 · Hard

   Eight months after an autologous stem cell transplant for IgG kappa myeloma, the original band has gone, but serum immunofixation shows two new faint bands, IgG lambda and IgM kappa, at other positions. Blood counts and calcium are normal, and no monoclonal antibody drug is given. The best interpretation is:

   1. AInterference from a therapeutic antibody
   2. BOligoclonal bands of immune recovery
   3. CRelapse of the original myeloma clone
   4. DFibrinogen from an incompletely clotted sample

   Show answerHide answer

   Answer: B · Oligoclonal bands of immune recovery

   After high-dose therapy and stem cell transplant, the recovering immune system often makes small, transient bands of different isotypes, called oligoclonal or abnormal protein bands. They differ in type or position from the original M-protein and are not a sign of relapse. They usually fade over months and should be reported as such, not as new disease. Relapse would show the original IgG kappa protein returning, often with a rising level or new organ damage.

   • A: No therapeutic monoclonal antibody is being given.
   • C: The original clone was IgG kappa; these bands differ in type and position.
   • D: Fibrinogen would not react with anti-IgG, anti-IgM or light-chain antisera.

6. Question 6 · Easy

   Compared with serum protein electrophoresis, immunofixation electrophoresis is used to:

   1. AMeasure the M-protein concentration in g/L
   2. BSeparate serum proteins by molecular size
   3. CMeasure serum free light chain concentrations
   4. DIdentify the heavy- and light-chain type of an M-protein

   Answer and explanation in LearnFree account