L21 Immunoglobulins and investigations of monogammopathy

Question 1

What is monoclonal gammopathy?

Answer 1

• Serum proteins = albumin + globulins
• Globulins
  1. alpha1 globulin
  2. alpha 2 globulin
  3. beta globulin
  4. gamma globulin includes immunoglobulin = Ab

Gammopathy =
single cone of plasma cells over-producing monoclonal immunoglobulins (e.g. IgG/IgA)

Question 2

Hypergammoglobulinemia can be differentiated into?

Why is it important to differentiate the 2?

Answer 2

1. Polyclonal - chrnonic inflammation/infection// autoimmune

2. Monocloncal - MGUS/MM/WM (Waldenstrom’s)&raquo_space;> requires TREATMENT

Question 3

What are the 2 characteristics of monoclonal gammopathy?

Answer 3

1. Reversed A:G ratio (increased Ig)

2. Majority produce IgG paraprotein, other plasma cell clones suppressed! (IgG > IgA)

Question 4

Multiple myeloma: reversed A:G ratio, also increased _________ due to increased Ig floating in blood.

What is used to diagnose MM?

Answer 4

Increased ESR;

BM biopsy
- increased clonal BM plasma cells >10%/ biopsy-proven plasmoctyoma

Question 5

What are the complications (end-organ damage) of MM?

Answer 5

CRAB

1. Hypercalcemia (adjusted Ca >2.75)
2. Renal insufficiency (Cr > 177umol/L // CrCl <40 ml/min)
3. Anemia (Hb<10)
4. Bone lesion (skeletal survey +/- MRI)

Question 6

What are the 3 hematological findings in MM patients?

Answer 6

1. Recurrent infections: H.influenzae/ Strep. pneumoniae due to immunosuppression/ chemotherapy
2. Bleeding symptoms: increase Ig bind to vWF > defect in platelet aggregation > bleeding tendency
3. Hyperviscosity syndrome: rare, due to hyperproteinemia

Question 7

What is the most common type of plasma cell dyscrasias?

Answer 7

MGUS

- monoclonal gammopathy of undetermined significance

Question 8

What are the differences of MGUS and MM?

Answer 8

1. Serum paraprotein <30g/L, BM clonal proteins <10%
2. No Bence Jones proteins in urine
3. no CRAB

Question 9

Which of the following is NOT a risk factor of MGUS to progress to MM?

A. Age >70 
B. High monoclonal protein concentration
C. IgG form
D. Abnormal FLC ratio
E. Detectable ligth chain proteinuira
F. Immunoparesis (immunosuppression)

Answer 9

C

non-IgG form!

Question 10

What is the current standard of test for monoclonal gammopathy? (2)

Answer 10

1. SPE (serum protein electrophoresis)

2. serum FLC

Question 11

Use of serum Ig pattern?

Can it be used to differentiate polyclonal/ monoclonal gammopathy?

Answer 11

Quantification of total IgA, IgG, IgM

No, requires SPE to differentiate!

Question 12

Which of the following about SPE is correct?
A. It detects monogammopathy because monoclonal proteins migrate at the same speed
B. It detects the presence of paraproteins and quantifies them
C. Paraprotein band size correlates with malignancy cell population size in BM
D. It quantifies paraproteins by their difference in densities
E. Serum Ig pattern can be seen

Answer 12

All of the above

Question 13

Use of SIFE (serum immunofixation electrophoresis)?

Answer 13

• Identification of monoclonal IgG heavy (G,A,M,D,E) and light chains (kappa/lamda)
  = M protein (e.g. IgG kappa)

Question 14

SIFE vs SPE, which is more sensitive?

Answer 14

SIFE is more sensitive, thus used as part of screening and confirmation of complete response to therapy

Question 15

What is urine protein electrophoresis (UPE) for?

Answer 15

1. Detection of Bence Jones proteins + quantify them
2. Identify kappa/lambda by urine IF

use 1st void of morning urine!

Question 16

Heavy and light cains are synthesied separately. _______ reflects plasma cell activity.

Answer 16

Free light chain

Question 17

What is the normal range of free light chain ratio? What does it mean when it is lower/ higher than the range?

Answer 17

kappa/lambda ratio (elevation of 1, suppression of the other)
Normal range: 0.26-1.65
<0.26 = lambda expression
>1.65 = kappa expression

Question 18

Which test has the highest sensitivity, in which it can identify 70% of non-secretory MM (undetectable by conventional SPE/SIFE).

Answer 18

Serum FLC

Question 19

Serum FLC concentration increases when? decreases when?

Answer 19

Increases

• renal impairment
• immune stimulation (e.g. autoimmune)
• monoclonal, biclonal/triclonal plasma cell proliferative disorders

Decreases
- immunosuppresion