Tuesday, November 17, 2009

kappa versus lambda light chains in paraproteinemias

Antibodies are comprised of the structure noted on the left:  they have two immunoglobulin heavy chains (in blue) and two immunoglobulin light chains (in green), covalently linked with one another via disulfide bonds (in red).  The light chains can be one of two types, either kappa or lambda; each individual B-cell (which synthesize and secrete clonal immunoglobulin) expresses either kappa or lambda, but not both, for the entire duration of its lifetime.  
Light chains play an important role in several nephrologic diseases.  They are small enough to be filtered at the glomerulus, but in normal conditions are reclaimed in the tubule.  When the resorptive capacity of the tubules are overwhelmed with extremely large amounts of light chain--as is the situation in paraproteinemias--then the light chains may appear in the urine, and potentially even cause damage as in the cast nephropathy.  Furthermore, certain light chains may accumulate in the glomerular basement membrane, causing glomerular disease (light chain deposition disease, LCDD), and still other light chains may be the underlying cause of AL amyloidosis.  

These different patterns of paraprotein-mediated disease tend to be mediated preferentially by either kappa or lambda light chains:

In cast nephropathy, lambda light chain is the most common.
In light chain deposition disease (LCDD), kappa light chain is the most common.
In AL amyloidosis, lambda light chain is the most common.

The typical kappa-to-lambda ratio in the normal human is about 65:35 (about 1:9), and this ratio is often altered in the above conditions.  It is especially important to look at the K:L ratio (rather than absolute values of K and L light chains) in patients with altered renal function, as the decreased GFR will directly lead to elevation in both K and L light chains.   

On a related note, Waldenstrom's macroglobulinemia is also a paraproteinemia, but rarely causes cast nephropathy or AL amyloidosis.  Interestingly, renal damage in this condition may well be caused by hyperviscosity syndrome.  



Amanda said...

Good Luck to you too! I know I've spent a lot of time "studying" on your website, I am ready for tomorrow to be over
The last few days topics, aminoglycoside, cryo, mpgn and now light chains are the EXACT holes I needed to fill... thanks!

Anonymous said...

From Multiple Myeloma Stephen M. Korbet* and Melvin M. Schwartz‡ Departments of *Medicine and ‡Pathology, Rush University Medical Center, Chicago, Illinois J Am Soc Nephrol 17: 2533–2545, 2006.

"Although it once was thought that renal failure more likely was associated with the excretion of lamda light chains (9,30), more recent studies find no
light-chain predominance (15,16,29).