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The data demonstrating polyclonal FLC increases due to increased production in inflammatory conditions, or reduced clearance in renal disease, is now well established. However, the utility of measuring polyclonal sFLCs (or ΣFLC) for diagnosis, monitoring, or prognosis needs to be confirmed with suitably designed further studies. The same could be said regarding the potential role(s) of FLC in disease pathology, and the possibility of FLCs as therapeutic targets. Hutchison and Langren [683] reviewed the literature concerning polyclonal FLCs as biomarkers of immune stimulation and inflammation. They speculated that sFLC measurement might, in the future, complement the use of CRP assays as a biomarker of inflammation, but concluded that more information was required before this could be advocated. They suggested this should include a better understanding of the intra-patient variation in FLC measurements (Section 7.2.6), of the relationship with CRP and other acute-phase proteins, and whether it is advantageous to correct sFLC measurements for renal clearance or use unmodified measurements (Section 6.3).

Brebner and Stockley [835] also reviewed the recent investigations of polyclonal FLCs as disease markers, bioactive molecules and potential therapeutic targets. They noted that the increasing use of B-cell targeted therapies for treatment of autoimmune disease, highlighted the potential of sFLC measurement for risk-stratification and monitoring responses. They also emphasised the requirement for further research such as large prospective studies to define the role of FLCs as predictors of mortality and the importance of determining whether, and where, FLC receptors exist.

Thus, although the study of polyclonal FLC elevations is an area of considerable interest and with an increasing number of publications, many important questions remain unanswered. Faint and colleagues [684] recently described the development of a new turbidimetric sFLC immunoassay that measures both κ and λ sFLCs simultaneously: producing a measurement of ΣFLC from a single assay. Hopefully, this will facilitate and encourage the further studies that are needed.

Questions

  1. Do conditions causing hypergammaglobulinaemia produce increases in sFLCs?
  2. Why are sFLCs highly elevated in patients with SLE?
  3. Suggest why measurement of FLCs may be useful in type 2 diabetes?
  4. What percentage of hepatitis C-infected patients have abnormal sFLCs?

Answers

  1. FLC production normally increases alongside increased production of the intact immunoglobulin molecules (Section 35.1).
  2. Because of increased production and reduced renal clearance (Section 35.4.1).
  3. Type 2 diabetic patients have significantly raised concentrations of serum and urinary polyclonal FLCs before overt renal disease occurs. Therefore, measurement of polyclonal FLCs could provide a useful tool in early diagnosis of diabetic kidney disease (Section 35.5).
  4. Nearly 50% if there is associated cryoglobulinaemia (Section 35.8.2).
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