Page 1115 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Monoclonal Gammopathies

Kazunori Murata, Samuel McCash, C. Ola Landgren

Monoclonal gammopathies are a group of disorders characterized Most cases of MGUS are sporadic. However, relatives of persons
by the proliferation of a single clone of plasma cells. These plasma with MGUS (or MM) have an increased risk of developing MGUS
cells produce an immunologically homogeneous immunoglobulin, and related diseases. Acquired angioedema is closely associated
or parts thereof, also known as an M (for monoclonal) protein. with MGUS, being identified in approximately one-third of
This chapter covers 12 recognized types of monoclonal gam- acquired angioedema patients. 1
mopathies: monoclonal gammopathy of undetermined signifi-
cance (MGUS); multiple myeloma (MM); smoldering multiple Clinical Presentation and Laboratory Findings
myeloma (SMM); nonsecretory/oligosecretory myeloma; plasma By definition, all patients with MGUS have no myeloma-associated
cell leukemia (PCL); solitary plasmacytoma of bone (SPB); solitary symptoms attributable to the proliferation of plasma cells or
extramedullary plasmacytoma (SEP); polyneuropathy, organo- the presence of the monoclonal protein. Non-IgM and IgM MGUS
megaly, endocrinopathy, monoclonal protein, skin changes are characterized by the presence of an M-protein produced and
(POEMS) syndrome; Waldenström macroglobulinemia (WM); secreted by clonal plasma cells. These proteins can be detected
heavy chain disease (HCD); light chain amyloidosis (AL); and in serum using either protein electrophoresis or immunofixation
monoclonal immunoglobulin deposition disease. These disorders electrophoresis as well as in a sample from a 24-hour urine
differ in the types of monoclonal proteins that are generated by collection using the same methods.
the diseased cell. The proteins involved include immunoglobulin The quantity of monoclonal protein in all cases of MGUS is
(Ig)-G, IgA, IgM, IgD, IgE, kappa or lambda light chains only, defined as <3 g/dL in the serum. Serum immunofixation elec-
and immunoglobulin heavy chains only. trophoresis (SIF) is used to confirm the presence of an M-protein
and to determine its type. The clonal immunoglobulin distribution
MONOCLONAL GAMMOPATHY OF in MGUS varies according to isotype: IgG 69%, IgM 17%, IgA
UNDETERMINED SIGNIFICANCE 11%, IgD <1%, and biclonal 3%. 2
IgD MGUS is extremely rare with only two cases having been
MGUS is a clinically asymptomatic premalignant clonal plasma reported. Thus finding an IgD M-protein is almost always associ-
cell or lymphoplasmacytic proliferative disorder. It is defined by ated with the diagnosis of MM, light chain amyloid, or PCL.
the presence of the following characteristics: the presence of an Biclonal MGUS is also uncommon, representing only 3% of
M-protein in the serum at a concentration <3 g/dL, bone marrow patients with MGUS. Approximately one-third of MGUS patients
with <10% monoclonal plasma cells, and the absence of end-organ will have a decrease in the concentration of the uninvolved
damage related to the lymphoproliferative process. There are immunoglobulin isotypes (e.g., IgM and IgA in the case of IgG
three distinct clinical types of MGUS: non-IgM MGUS, IgM MGUS), with many demonstrating a reduction in the normal
MGUS, and light chain MGUS (LC-MGUS). polyclonal circulating immunoglobulins. 1
Serum free light chain (sFLC) assays can detect low concentra-
Epidemiology tions of monoclonal free light chain in patient serum. This
MGUS occurs in approximately 1–2% of adults and >2% of the technique can be used to diagnose light chain MGUS and to
general Caucasian population above the age of 50. The mean predict the risk of the progression of MGUS. A monoclonal light
age at diagnosis is 70 years with <2% of patients diagnosed chain can also be found in the urine of approximately 20% of
before the age of 40. The incidence increases with age, and the MGUS patients. 1
prevalence of MGUS in persons ≥50, ≥70, and ≥85 years of age The complete blood count and peripheral smear are typically
is 3.2%, 5.3%, and 7.5%, respectively. 1 normal. Infrequently, rouleaux formation (the phenomenon in
Men are at higher risk of developing MGUS compared with which red cells take on the appearance of stacked coins in diluted
women (4.0% versus 2.7%). The incidence of MGUS in men is suspensions of blood) is seen, and this is typically observed in
estimated to be 120/100 000 at age 50, increasing to 530/100 000 those MGUS patients with elevated serum protein levels. Circulat-
by the age of 90, whereas the incidence rate for women is estimated ing plasma cells of the same isotype can be seen in peripheral
to be 60/100 000 at age 50, increasing to 370/100 000 by the age blood of some patients with MGUS using a slide-based immu-
of 90. Race is also a risk factor, with the incidence of MGUS nofluorescence assay or flow cytometry. 1
being 1.5- to 3-fold higher in Africans and African Americans By definition, a bone marrow aspirate and biopsy must
compared with Caucasians. 1 demonstrate fewer than 10% clonal plasma cells. For IgM

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