What is kappa (κ) light chain?

From the Guidelines

Kappa light chain is a crucial protein component in antibodies, with approximately 60% of antibodies in humans containing kappa light chains, playing a vital role in the immune system by recognizing and binding to specific antigens. The kappa light chain is a type of protein component found in antibodies and immunoglobulins in the human body, consisting of two heavy chains and two light chains, with the light chains being either kappa or lambda type 1. These light chains play a crucial role in the immune system by helping antibodies recognize and bind to specific antigens. In certain blood disorders like multiple myeloma or light chain amyloidosis, plasma cells may produce excessive amounts of free kappa light chains not attached to complete antibodies, which can be detected through serum free light chain assays, measuring the ratio of kappa to lambda chains 1. An abnormal ratio often indicates underlying disease, and monitoring kappa light chain levels is important for diagnosing these conditions, tracking disease progression, and evaluating response to treatment in patients with plasma cell disorders. Key factors to consider when evaluating kappa light chain levels include:

• The production and secretion of an M-protein, which is mostly an intact immunoglobulin that can be quantified and specified by serum electrophoresis and immunofixation 1
• The presence of serum free light chain production, which frequently accompanies the intact immunoglobulin but can be the dominant or exclusively produced paraprotein in 15–20% of patients 1
• The use of serum free light chain assays to measure the ratio of kappa to lambda chains, which can help diagnose and monitor plasma cell disorders 1.

From the Research

Definition and Structure of Kappa Light Chain

• Kappa light chain is a component of immunoglobulin molecules, which are generated by a pair of identical heavy chains and a pair of identical light chains, either Kappa or Lambda 2.
• In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound 2.

Clinical Significance of Kappa Light Chain

• Kappa light chain defects are rare and can lead to immunoglobulin disorders, resulting in serious recurrent bacterial infections 2.
• The measurement of serum free light chains, including Kappa, has been shown to be valuable in screening for plasma cell dyscrasia and for baseline prognosis in newly diagnosed patients with multiple myeloma 3.
• Kappa light chain production has been observed in patients with multiple myeloma, with a ratio of Kappa to Lambda chains of 43:33 4.
• Free Kappa light chains have been implicated in various immunological phenomena, including signaling and anti-inflammatory effects 5.

Preclinical and Clinical Development of Anti-Kappa Therapies

• Monoclonal antibodies targeting Kappa free light chains have been developed for the treatment of multiple myeloma, including MDX-1097, which is currently in Phase II clinical trials 6.
• The preclinical and clinical development of these therapies aims to provide new treatment options for patients with multiple myeloma, a disease with limited approved monoclonal antibody therapies 6.