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The Significance of Polyclonal Light Chains in Cases of Rheumatoid Arthritis

written by: efrontiers • edited by: Emma Lloyd • updated: 4/25/2011

Based on several studies, there is a pathological relationship between high polyclonal free light chains (or FLC) concentrations and rheumatoid arthritis. Hence, the significance of polyclonal light chains in rheumatoid arthritis might be as one of the early indications of the disease.

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    The Antibody

    An antibody, more specifically referred to as an immunoglobulin, is a Y-shaped protein that aids the immune system in identifying foreign bodies such as viruses and bacteria. The basic structure of antibodies is made up of two large heavy chains and two small light chains.

    In humans, there are two types of immunoglobulin light chains. These are the lambda chains and kappa chains. In a typical antibody, there is only one type of light chain present. Therefore, the antibody’s two light chains are identical.

    Each smaller polypeptide light chain in an antibody molecule consists of two tandem domains, the variable antigen-binding part and the constant region. The antigen-binding component has a variable amino acid sequence while the constant region has an unchanging amino acid sequence. In the antibody structure, the light chains are connected to the heavy chains. This order allows the variable regions of the two smaller light chains to lie alongside each other.

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    What are Polyclonal Light Chains?

    Immunoglobulin light chains are secreted by B-cells. Polyclonal light chains are combination of immunoglobulin molecules obtained from different B-cell resources. Due to the immune response against a certain antigen, the activation of multiple B-cells produces these antibodies. Each of these light chains is secreted to target a specific epitope on the antigen.

    Under normal conditions, polyclonal light chains, in their free forms, are usually present in the serum of adults at low concentrations. Both the lambda and kappa chains are metabolized by the kidney. Hence, these polyclonal light chains appear in very small amounts in the urine.

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    Polyclonal Light Chains and Rheumatoid Arthritis

    Studies reported that many rheumatic diseases are associated with generalized increase in polyclonal B-cell activation, high concentrations of autoimmune antibodies, and coexisting high polyclonal serum free light chains, or sFLCs. The manifestation of excessive polyclonal FLCs in urine may be useful in the early detection of rheumatic diseases. Nevertheless, serum analysis of FLCs may be more recommended due to higher reliability.

    Based on a study headed by Hoffman (2003), there are certain rheumatic diseases that showed significantly high FLC concentrations when compared to patients with fibromyalgia or the control group. These diseases include rheumatoid arthritis, vasculitis, systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis. This information will specifically take a closer look at the role of increased polyclonal light chains in rheumatoid arthritis.

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    Increased FLCs in Rheumatoid Arthritis

    In a study by Gottenberg and team, 36% of the 50 patients with rheumatoid arthritis had elevated sFLCs. This resulted in mean values that have significant differences compared to the control group without rheumatoid arthritis. Furthermore, related studies support the correlation between B-cells and disease activity.

    A larger study further investigated the levels of polyclonal light chains in rheumatoid arthritis patients. In 710 patients, researchers found that the levels of FLCs, together with other markers of B-cell activation, were higher in early stages of rheumatoid arthritis compared to undifferentiated arthritis. This led to the conclusion that B-cell activation is a reliable indicator of rheumatoid arthritis.

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    Conclusion

    In conclusion, polyclonal light chains play a significant role in the early detection of rheumatoid arthritis. This is because free light chains serve as indicators of increased disease activity in rheumatic diseases such as rheumatoid arthritis. This link can be of great help to researches in the testing and development of new drugs for rheumatoid arthritis.

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    References

    Bradwell AR. Editorial: Clinical importance of serum free light chain analysis. Personalized Medicine 2010;7:229-31

    Hoffman U, Opperman M, Kuchler S, Ventur Y, Teuber W, Michels H, et al. Free immunoglobulin light chains in patients with rheumatic diseases. Zeitschrift für Rheumatologie 2003;62:Fr40a

    Janeway CA, Jr. et al. (2001). Immunobiology. (5th ed.). Garland Publishing.

    http://www.nature.com/ki/journal/v63/n84s/full/4493759a.html

    http://www.ncbi.nlm.nih.gov/pubmed/12194920

    http://www.ncbi.nlm.nih.gov/pubmed/16569685

    http://www.ncbi.nlm.nih.gov/pubmed/19627580

    http://www.randox-lifesciences.com/Article/ViewArticle/57?path=Polyclonal%20vs.%20Monoclonal&20Antibodies&articleSectionId=1

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