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Systems: Haematology + Immunology > Myeloma > Flashcards

Myeloma Flashcards

1
Q

What are immunoglobulins?

A

Antibodies

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2
Q

What are Ig produced by?

A

B cells, mostly plasma cells (terminal cells of B cell maturation)

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3
Q

What is the primary role of Ig?

A
  • Recognise and bind to pathogens
  • This may directly impede the biological process or direct other components of the immune system by ‘tagging’ the antigen
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4
Q

What is the basic structure of Ig?

A
  • Soluble or membrane bound
  • Y shaped
  • 2 heavy chains
  • 2 light chains
  • Variable domains
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5
Q

What is the Fc portion of Ig defined by?

A

Heavy chains

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6
Q

What are the 5 types of heavy chain?

A
  • IgG: Gamma
  • IgA: Alpha
  • IgM: Mu
  • IgD: Delta
  • IgE: Epsilon
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7
Q

What is a feature of IgG?

A

Most prevalent antibody subclass

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8
Q

What type of immunity is IgA involved in?

A

Mucous membrane immunity

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9
Q

What are the features of IgM?

A
  • Initial phase of antibody production
  • Exists as a pentamer – highest molecular weight
  • Viscous
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10
Q

What is IgE involved in?

A
  • Parasite immune response

- Hypersensitivity

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11
Q

What are the 2 types of light chains?

A

Kappa or lamda

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12
Q

How are kappa and lamda selected?

A
  • Random selection for each cell

- But, each cell will only make 1 type of light chain with 1 specificity

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13
Q

Where can free light chains be found?

A

In the blood at low levels but they are difficult to measure

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14
Q

What does the FC region define?

A

Constant region that defines subclass

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15
Q

What does the Fab region define?

A

Variable region that defines target binding

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16
Q

What are the total levels of Ig in the blood?

A
  • IgG: 6-15g/l
  • IgA: 1-4.5g/l
  • IgM: 0.5-2g/l
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17
Q

What is a paraprotein?

A

A monoclonal immunoglobulin present in blood or urine

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18
Q

What do paraproteins tell us?

A

If present, it tells us that there is monoclonal proliferation of a B lymphocyte / plasma cell somewhere in the body

19
Q

What does serum protein electrophoresis do?

A
  • Separates protein based on size and charge
  • Forms a characteristic pattern of bands of different widths and intensities based on proteins present
  • There will be a spike in the gel if there is a paraprotein present
20
Q

What do total immunoglobulin levels tell us?

A

Measures Ig subclasses by heavy chain/Fc section

21
Q

What does electrophoresis tells us?

A

Assesses antibody diversity and identifies paraprotein

22
Q

What does immunofixation do?

A

Identifies what class of paraprotein is present

23
Q

What do light chains tell us?

A

Assesses imbalance/excess of light chains in urine or serum such as Bence-Jones protein

24
Q

What do IgM paraproteins suggest and why?

A

Lyphoma

-Maturing B-lymphocytes make IgM antibody at the start of the immune response

25
Q

What do IgG and IgA paraproteins suggest and why?

A

Myeloma

-Mature plasma cells generate these types of Ig after isotope switching

26
Q

What is myeloma?

A

Neoplastic disorder of plasma cells, resulting (usually) in excessive production of a single type of Ig (paraprotein)

27
Q

When does myeloma incidence peak?

A

7th decade (commoner in black populations)

28
Q

What may cause the clinical manifestations of myeloma?

A

Direct effect of plasma cells or effect or paraprotein

29
Q

What are the clinical features of myeloma?

A

Bone disease

  • Lytic bone lesions
  • pathological fractures
  • Cord compression
  • Hypercalcaemia

Bone marrow failure including anaemia

Infections

30
Q

When does myeloma occur?

A

-Myeloma occurs when there is no normal Ab production left and overgrowth of the abnormal Ab

31
Q

What effects can paraproteins have?

A
  • Renal failure (cast nephropathy)
  • Hyper viscosity
  • Hypogammaglobulinaeemia
  • Amyloidosis
32
Q

Why can renal failure occur on myeloma?

A

Ig deposition and blockage of renal tubules

33
Q

How does hyper viscosity associated with myeloma present?

A
  • Syndrome caused by increased viscosity in blood, impaired microciculartion and hypoperfusion
  • Commonest clinical feature is bleeding – retinal, oral, nasal, cutaneous
  • Can also cause cardiac failure, pulmonary congestion, confusion, renal failure
34
Q

Why does hypogammaglobulinaemia occur in myeloma?

A

Impaired production of normal IG leads to a tendency to infection

35
Q

What is amyloidosis?

A

-A group of disorders characterised by deposition of firbillar protein (abnormal configuration of proteins)

36
Q

What is amyloidsosi caused by paraprotein of light chains known as?

A

AL amyloid

37
Q

How does AL amyloidosis present/?

A
  • Nephrotic syndrome
  • Cardiac failure (LVH)
  • Carpal tunnel syndrome
  • Autonomic neuropathy
  • Cutaneous infiltration
38
Q

How is myeloma diagnosed?

A
  • Finding excess plasma cells in the bone marrow
  • Must comprise >10% of total bone marrow cell population
  • Staging based on albumin and beta-2 microglobulin
39
Q

What is monoclonal gammopathy of uncertain significance (MGUS)?

A

Paraproteins that are present in 3-4% of the over 75 population that are not pathological

40
Q

What types of paraprotein are implicated in myeloma?

A
  • IgG: 55%
  • IgA: 21%
  • Light chain only 22%
  • Other: 2%
41
Q

How is myeloma treated?

A
  • Chemo: proteasome inhibitors. thalidomide, monoclonal antibodies
  • Bisphosphonate therapy: zoledronic acid
  • Radiotherapy
  • Steroids
  • Surgery: pinning of long bones, decompression of spinal cord
  • Autologous stem cell transplant
42
Q

What are IgM paraproteins associated with?

A

Low-grade lymphomas

43
Q

What is the clinical presentation of IgM paraproteins?

A
  • Bone marrow failure (anaemia, thrombocytopenia)
  • Lymphadenopathy
  • Hepatosplenomegaly
  • B symptoms
  • Paraprotein-related symptoms can occur
  • Bone disease is very rare

Systems: Haematology + Immunology (19 decks)

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