This review article explores multiple myeloma, cardiovascular disease, inflammatory response and how each disease alters the proteins found in blood serum. I also explore the factors effecting albumin.
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Diseases and factors that affect serum protein in humans
Introduction
What is blood serum?
Blood plasma has leukocytes and erythrocytes suspended in it, as well as having a high
protein content. When blood is allowed to clot and centrifuged, a liquid serum is produced, in
which is made up of around 7% protein and excludes fibrinogen and clotting factors. About
half of the proteins making up serum is albumin. Albumin consists of a single peptide chain,
585 amino acids in length, has a globular structure and is imperative in the maintenance of
oncotic pressure and it does this essentially, by preventing the leakage of water out of the
blood (Rothschild et al., 1988). Albumin is also used in the transportation molecules such as
fatty acids and hormones (Rothschild et al., 1988) (Carter and He, 1990).
Generally why do serum protein levels change?
For example, a disorder may cause particular proteins to be under or over expressed (such
as M protein presence in individuals with multiple myeloma), Increase, decrease or cause
proteins to not be present in blood serum (Kyle and Rajkumar, 2008). Damage to organs can
cause particular proteins usually found within a particular organ to seep into the blood, or
protein can even be effected by non-disease related factors such as age, sex and pregnancy
(Prieto et al., 1975). This article will look into how proteins within the serum are altered by
particular conditions and factors.
Table 1. The typical concentrations of proteins in serum and response to acute phase
reactions (Ahmed, 2017, 447).
Normal concentration of proteins in serum (g/L)
Protein Reference Response to an acute phase
range reaction
Total protein 63 - 83 No response
Albumin 32 - 48 Decline
a1-Antitrypsin 0.9 - 1.8 Rise
A1-Acid 0.4 - 1 Rise
glycoprotein
Haptoglobin 0.5 - 2.6 Rise
Caeruloplasmin 0.2 - 0.6 Rise
Transferrin 1.9 - 3.5 Decline
Complement 0.8 - 2.14 Rise
C3
Complement 0.13 - 0.6 Rise
C4
IgG 6 - 13 No response
IgA 0.8 - 3.7 No response
IgM 0.4 - 2.2 No response
Multiple myeloma
Multiple myeloma (MM) is cancer of the bone marrow where uncontrolled division of plasma
cells occurs and is a monoclonal gammopathy, meaning that abnormal immunoglobulins are
found in the blood (Kyle and Rajkumar, 2008). B2M is a component of class 1 MHC and is
usually increased in individuals with MM, lymphoma and leukaemia (Kyle and Rajkumar,
2008). MM can also lead to an increase of serum free light chain (in around 15% of
individuals) and decrease in gamma globulins and this is due to the malignant plasma cells
only producing light chains of the antibodies (Rafae et al., 2018).
MM can be diagnosed using urine, calcium or serum protein levels (Bird et al., 2011). Using
densitometry to quantify the serum M-protein peak produced in electrophoresis and carrying
, out a bone marrow assessment, allows for diagnosis and monitoring myeloma when light
chains are present (Bird et al., 2011).
Table 2. Monoclonal gammopathy of undetermined significance (MGUS), asymptomatic and
symptomatic myeloma diagnosis measures (Bird et al., 2011).
MGUS Asymptomatic myeloma Symptomatic myeloma
Serum M-protein <30 g/l Serum M‐protein ≥3 g/l Serum M-protein and or in
the urine
Plasma cells in the bone Bone marrow clonal plasma Clonal bone marrow plasma
marrow <10% and low level cells ≥10% cells or confirmed
of plasma cell penetration in plasmacytoma
a trephine surgery
No associated organ or No associated organ or Myeloma related organ or
tissue damage tissue damage or signs tissue damage (such as
bone neoplasms)
Incidence of MM differs on a few factors like age and the stages of multiple myeloma can be
determined by measuring serum β2-microglobulin (B2M) and serum albumin levels, but they
cannot be used in diagnosis of MM (Kyle and Rajkumar, 2008).
Table 3. Multiple myeloma international staging system (Kyle and Rajkumar, 2008)
Phase 1
β2-microglobulin in serum less than 3.5 mg/l
Albumin greater than or equal to 3.5 g/100 ml
Phase 2
Does not fit into stage 1 or 2
Phase 3
β2-microglobulin in serum greater than or equal to 5.5 mg/l
If the patient has low gamma globulin serum levels (hypogammaglobulinemia) they are more
prone to infection, so in order to increase levels, gamma globulins are administered by IV
every 3-4 weeks (Rafae et al., 2018).
Figure 1. The structure of an IgG (Absolute Antibody, 2015)
Blue signifies the heavy chain and green represents the light chains.
Cardiovascular disease
Cardiac troponin T(cTnT) and cardiac troponin I (cTnI) are typical biomarkers of heart
muscle damage (Apple, 2009). CTnT becomes elevated around 3 to 4 hours after injury to
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