Q. Why do light chains appear in the urine in mu heavy chain disease but not in alpha or gamma heavy chain diseases?

A. Heavy chain diseases (HCDs) are B-cell proliferations in which the cells produce abnormal immunoglobulin heavy chains. The cells can produce any type of heavy chain they want except IgE (at least it’s never been described).

Alpha HCD, in which the B cells produce heavy chains resembling those of IgA molecules, is the most common HCD (HCD itself being pretty uncommon). It tends to occur in younger patients; many are in their 30s. Gamma HCD, also called Franklin disease after the first person to report the disease, frequently occurs in association with autoimmune disorders like rheumatoid arthritis and lupus. The prognosis is not so great, with survival on the order of months to a few years. Mu chain disease is very rare, and the prognosis is more variable, on the order of months to many years.

As far as your question goes: you’re right: you can see light chains in the urine of patients with mu HCD, but you don’t see them in patients with alpha or gamma HCD. In mu HCD, the B cells produce light chains, but they can’t be attached to the mu heavy chains because there are abnormalities in the mu chains that prevent the assembling of complete Ig molecules. So – the light chains that are formed are free to be filtered into the urine.  In alpha and gamma HCD, you don’t see light chains in the urine because the B-cells in these disorders only make heavy chains – no light chains at all.