Role of the clinical immunology laboratory in disease monitoring

Table 1 A summary of clinically relevant antibodies targeted against glycolipid and glycoprotein-related saccharides

Neuropathy syndrome	Antibody target	Antibody isotype
Chronic Sensory-Motor demyelinating	Myelin-associated glycoprotein Sulfoglucuronylparagloboside	IgM (monoclonal)
Chronic ataxic neuropathy	GD1b, GQ1b	IgM (monoclonal)
Multifocal Motor neuropathy	GM1, GM2, GD1b	IgM (polyclonal or monoclonal)
Sensory neuropathy	Sulfatide	IgM (monoclonal or polyclonal)
Acute motor axonal neuropathy	GM1, GD1a, GalNAc GD1a, GM1b	IgG
Acute inflammatory demyelinating polyneuropathy	Variable	Variable
Miller-Fisher syndrome	GQ1b ("anti-GQ1b antibody syndrome"), GT1a	IgG
Bickerstaff's brainstem encephalitis
Acute ophthalmoparesis
Ataxic Guillain-Barré syndrome
Pharyngeal-cervical-brachial weakness	GT1a (GQ1b)	IgG
Amyotrophic lateral sclerosis	GM1	IgG

Modified from http://www.aetna.com/cpb/medical/data/300_399/0340.html (Accessed December 8, 2012). IgM: Immunoglobulin M; IgG: Immunoglobulin G.

Table 2 Common clinical associations of paraproteins[70]

Disorder	Diagnostic features
Monoclonal gammopathy of undetermined significance	All three criteria must be met:
	Serum monoclonal protein < 30 g/L
	Clonal bone marrow plasma cells < 10%
	Absence of end-organ damage ("CRAB"), e.g., hypercalcemia, renal insufficiency, anaemia and bone lesions due to the plasma cell disorder
Smouldering myeloma	Both criteria must be met:
	Serum monoclonal protein (IgG or IgA) > 30 g/L and/or clonal bone marrow plasma cells > 10%
	Absence of "CRAB", as defined above
Multiple myeloma	All three criteria must be met:
	Clonal bone marrow plasma cells > 10%
	Presence of serum and/or urinary monoclonal protein (except in patients with true non-secretory multiple myeloma)
	Evidence of "CRAB", as defined above
Waldenström’s macroglobulinaemia	Both criteria must be met:
	IgM monoclonal gammopathy and
	10% bone marrow infiltration (usually intertrabecular) by lymphoplasmacytic cells (morphology/immunophenotype)1
IgM monoclonal gammopathy of undetermined significance	All three criteria must be met:
	Serum IgM monoclonal protein < 30 g/L
	Bone marrow lymphoplasmacytic infiltration < 10%
	No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly
Smoldering Waldenström’s macroglobulinemia	Both criteria must be met:
	Serum IgM monoclonal protein > 30 g/L and/or bone marrow lymphoplasmacytic infiltration > 10%
	No evidence of end-organ damage such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly due to a lymphoplasma cell proliferative disorder

¹Note that other clonal B-cell disorders may be associated with paraproteins and may require careful clinical, morphological and immunophenotypic assessment for diagnosis (e.g., chronic lymphocytic leukaemia, mantle cell lymphoma, etc.). IgM: Immunoglobulin M; IgG: Immunoglobulin G; CRAB: Hypercalcemia, renal insufficiency, anaemia and bone lesions.