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Immunoglobulin heavy/light chain (Hevylite®, HLC) assays separately quantify the different light chain types of each immunoglobulin isotype (i.e. IgGκ, IgGλ, IgAκ, IgAλ, IgMκ and IgMλ, Chapter 9). HLC assays are performed on routine nephelometric or turbidimetric instruments (Chapters 9 and 38). The molecules are assessed in pairs to produce HLC ratios (e.g. IgGκ/IgGλ) in the same manner as κ/λ sFLC ratios. HLC assays provide an alternative tool to aid in the management of diseases associated with monoclonal intact immunoglobulins, including monoclonal gammopathy of undetermined significance (MGUS), SMM and intact immunoglobulin multiple myeloma (IIMM) (Chapters 13, 14, and 18).

HLC assays may overcome many of the known limitations of serum electrophoresis (including co-migration and dye saturation) and are less labour-intensive and less subjective. The sensitivity of the HLC ratio to detect monoclonal intact immunoglobulins is dependent upon the concentration of both the involved and uninvolved immunoglobulin HLC. In a study of 999 patients with MGUS, IgA and IgM HLC assays were generally as sensitive as SPE, whereas IgG HLC assays did not identify a monoclonal immunoglobulin in almost half of patients, presumably due to the lack of polyclonal uninvolved HLC suppression [123]. By contrast, Katzmann et al. [38] demonstrated that whilst IgG HLC assays had a similar sensitivity to SPE for the detection of IgG monoclonal proteins in sera from IgG MM patients (n=155, Table 4.3), the sensitivity of IgA HLC assays was greater than SPE and comparable to that of IFE for IgA monoclonal proteins in IgA MM patient sera (n=149, Table 4.4). The authors concluded that IgA HLC assays can substitute for the combination of SPE, IFE and total IgA quantification for monitoring β-migrating IgA monoclonal proteins.

Serum sample n Abnormal
SPE*
Abnormal
IgGκ/IgGλ HLC ratio
Presentation 32 31 (97%) 30 (94%)
Post-treatment 123 104 (85%) 106 (86%)
All 155 135 (87%) 136 (88%)

Table 4.3. SPE and HLC ratio abnormalities in IgG MM [38]. Data are n (%); * Monoclonal protein band or small, fuzzy band.

Serum sample n SPE monoclonal protein
quantified
Abnormal
IgAκ/IgAλ HLC ratio
Positive
IFE
Total IgA
>upper limit of normal*
Presentation 30 23 (78%) 29 (97%) 30 (100%) 26 (87%)
Post-treatment 119 18 (15%) 54 (45%) 56 (50%) #48 (40%)
All 149 41 (28%) 83 (56%) 86 (61%) 74 (50%)

Table 4.4. SPE, HLC, IFE and total IgA abnormalities in IgA MM [123]. Data are n (%); * >3.56 g/L; # n=111; † n=141.