At times, light chains of either kappa or lambda type may form tetramers (88,000?D), which are not filtered, and a patient may have light chain proteinemia without light chain proteinuria
At times, light chains of either kappa or lambda type may form tetramers (88,000?D), which are not filtered, and a patient may have light chain proteinemia without light chain proteinuria. GW2580 The kidney is the major site of metabolism of light chain proteins. case is usually reported here as the light chain variant of multiple myeloma leading to deposition disease is usually less generally reported and presents considerable difficulties in diagnosis. corresponds to band Open in a separate windows Fig.?2 Serum immunofixation depicting Ig kappa Open in a separate windows Fig.?3 Urine protein electrophoresis; corresponds to band Open in a separate windows Fig.?4 Urine immunofixation depicting light chain Kappa Conversation Light chains (molecular weight 22,000?D) are polypeptides synthesized by plasma cells and assembled with heavy chains to form the various classes of immunoglobulins, for example, IgG, IgM, and IgA. Plasma cells normally produce a slight excess of light chains that are either excreted or catabolized by the kidney . Light chains are divided into two major classes based on the amino acid GW2580 sequence in the constant portion of the polypeptide chain and are designated as kappa and lambda. These are further divided into at least ten subtypes (four kappa and six lambda) based on the amino acid sequence in the variable region of the polypeptide chain. Individual immunoglobulins have either kappa or lambda light chains, but not both. Kappa light chains usually exist as monomers GW2580 (22,000?D) and are therefore small plenty of to be filtered through the glomerulus, but they may exist as dimers. Lambda light chains GW2580 usually exist as dimers (44,000?D) and, therefore, are less likely to be filtered and appear in urine. At times, light chains of either kappa or lambda type may form tetramers (88,000?D), which are not filtered, and a patient may have light chain proteinemia without light chain proteinuria. The kidney is the major site of metabolism of light chain proteins. The filtered light chain proteins, reabsorbed by the proximal tubular cells via the tandem megalin/cubilin receptors, are catabolized by lysosomal enzymes. This process is usually exceedingly efficient, and only a minute amount of light chain protein normally appears in the urine. Metabolism (catabolism) of these filtered light chain proteins depends on normal proximal tubular cell function, and damage to these cells can result in increased excretion of light chain proteins in the urine. Hence, light chain proteins appear in urine in high concentration either when the production of light chain proteins is usually markedly increased or when the ability of the proximal tubules to reabsorb all the filtered protein is usually exceeded. Structural gene loss involving the deletion of the JCH segment of the heavy chain locus (situated on chromosome 14) is the most probable cause leading to isolated production of light chains in the disease. Light chains cause rapid decline of renal function and early onset of clinical deterioration in LCD. Renal damage caused by the freely filtered light chains affects every segment of the nephron. In the glomerulus, they can cause a non fibrillary glomerulopathy including deposition of light chains as well as fibrillary glomerulopathy characterised by amyloidosis. In the proximal tubules, reabsorption prospects to formation of harmful metabolites and an acquired Fanconi syndrome. The distal tubules suffer what has been termed cast nephropathy as a result of epithelial damage due to cast formation in the lumina. Proteinaceous casts are prominent in the distal convoluted tubules and collecting ducts. Some of the casts are surrounded by multinucleated giant cells derived from fusion of infiltrating macrophages. The laboratory features of LCD are different from classical myeloma and hence present considerable challenge to diagnosis . The serum total protein is normal to low. Hypogammaglobulinemia is commonly encountered as opposed to hypergammaglobulinemia seen in classical multiple myeloma. This is because of the fact that only light chains are produced which because of their low molecular excess weight are easily filtered out by the kidneys. 100% of the patients show evidence of BenceCJones protein. Many patients do not have a serum M Rabbit Polyclonal to MED27 (monoclonal) component on electrophoresis as most light chains are quickly filtered by the kidneys. Urine electrophoresis therefore becomes an important test in such cases. Urine immuno fixation electrophoresis discloses the type of monoclonal component present GW2580 in case it is not detected by serum. The usual picture in the disease populace reveals kappa: lambda ratio of 2:1. This variation is important because lambda LCD has a three times worse prognosis than kappa LCD..