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Bence Jones protein refers to a urinary protein that leaves the solution at approximately 56^oC under particular conditions of ionic strength and pH and returns to the solution on further heating to 100^oC. It represents a homogeneous population of kappa or lambda-type light chains. The presence of these immunoglobulin light-chain proteins in the urine is linked to several systemic diseases. Bence Jones protein (BJP) was first described in 1845 in a patient admitted to St. George’s Hospital in London with vague continuous pain in the chest, back, and pelvis. Dr. Henry Bence Jones tested the patient's urine and found a substance precipitated by adding nitric acid. Jones proceeded to call this substance “hydrated deutoxide of albumen.” All types of proteinuria were referred to as albuminuria at that time. The autopsy of this patient revealed that his sternum and vertebrae were soft and fragile, and multiple hemorrhagic cavities were present in the bone. The cause of death was noted to be “atrophy from albuminuria.” The term Bence Jones protein was first used in 1880 by Dr. Fleischer.[1] Its peculiar characteristics on heating first characterized BJP: precipitation of the urine at 40 to 60^oC and re-dissolving of the precipitate at 100^oC.[2][3] While this seminal observation led to the first description of multiple myeloma (MM), it did not hold up to scrutiny over time. Today BJP is known as the light chain of immunoglobulins without the accompanying heavy chain and can be accurately quantified by electrophoretic techniques, including immunofixation electrophoresis (IFE). The other crucial teaching point is that BJP is undetectable by dipsticks used to detect proteinuria since they detect albumin and not BJP.[4] In this brief review, we describe the evolution of BJP, its biochemistry, and its high clinical relevance. In 1939 Longworth applied electrophoresis for the first time in the study of multiple myeloma. In 1953 Grabar and Williams described the methods of immunofixation and direct immunoelectrophoresis, which increased the detection of small monoclonal light chains not detectable on basic gel electrophoresis; this is the classic “M spike” seen in the gamma region in patients with MM. In 1956, Korngold identified the two classes of BJP: Kappa and Lambda light chains.[5]

In 1939 Longworth applied electrophoresis for the first time in the study of multiple myeloma. In 1953 Grabar and Williams described the methods of immunofixation and direct immunoelectrophoresis, which increased the detection of small monoclonal light chains not detectable on basic gel electrophoresis; this is the classic “M spike” seen in the gamma region in patients with MM. In 1956, Korngold identified the two classes of BJP: Kappa and Lambda light chains.[5] In 1962, Drs. Edelman and Porter received the Nobel Prize in Physiology or Medicine for their work elucidating the chemical structure of antibodies. The M-spike of a particular patient with MM was broken into heavy and light chains. Edelman demonstrated that the light chains of this M-spike were identical to the BJP that the patient excreted in his urine. He expanded on this work by comparing reduced myeloma proteins from different patients. When each of these proteins was reduced, alkylated, and put through starch gel electrophoresis, they exhibited a unique migration pattern. Similar to BJP, when Edelman heated samples containing light chains from normal human serum gamma globulins, they became insoluble and re-solubilized with continued heating. In 1967, Dr. Putnam demonstrated that different BJPs had distinct peptide sequences. This differentiation further supported Dr. Edelman’s observation that no two BJPs “had the same mobility pattern.”[3] Bence Jones protein, or free light chains, are found in the urine as low molecular weight monomers, dimers, or high molecular weight polymers. Contrastingly, Bence Jones proteins are present in the serum as tetramers. Their molecular weight is approximately 22000 Daltons, and the kidney metabolizes them through glomerular filtration, proximal renal tubular absorption, and renal catabolism. Bence Jones proteins spill into the urine once the capacity for tubular reabsorption becomes saturated.[6]

The presence of light chain ladders in samples is a complicating phenomenon. Polyclonal light chains, usually kappa, can produce a characteristic banding pattern after electrophoresis and immunofixation electrophoresis. These light chain ladders are not Bence Jones proteins but commonly appear in the urine samples of elderly patients suffering from tubular proteinuria due to inflammatory disease. Moreover, Bence Jones proteins can sometimes co-migrate with the bands in these ladders. These ladders must be carefully examined to ensure no concomitant accompanying Bence Jones proteins. However, the clinical presentation and other investigative findings help confirm the presence of the BJP.[6]