Plasma Cell Dyscrasia Associated With the Production of

The clinical, hematologic, and immunoglobulin features of a new form of plasma cell dyscrasia (deleted H and L chain disease) are described. The clinical manifestations are periodic fever and weakness, lymphadenopathy, and hepatosplenomegaly. The hematologic abnormalities are anemia, leukopenia, lymphocytosis, thrombocytopenia, and increased plasma cells in lymph nodes and bone marrow. The protein abnormalities have been identified as (1) monoclonal lgG,A serum globulin (5-6 g/l00 ml) with deletions in both H and L chains and an estimated mol wt of 110,000; (2) free y Fc fragment in serum and urine; (3) urinary excretion (10-20 g/day) of deleted A-chains (UX) with an estimated mel wt of 15,000. UX and the AL chains of the IgG are apparently identical. UA was shown to contain approximately 26 moles of carbohydrate, with an average of 2.2 moles of sialic acid per 15,000 mol wt. UA displayed marked electrophoretic heterogeneity which was related to a variable number of sialic acid residues. The N terminus of UX is blocked (PCA). The deletions of both the Aand the H chains were localized to their respective V regions and are of similar magnitudes (approximately 10,000 daltons). Possible genetic mechanisms to explain apparently comparable Hand L-chain deletions in a single IgG molecule are considered. I N RECENT YEARS, increased knowledge of the detailed structure of immunoglobulins has enabled the identification and characterization of several specific types of plasma cell dyscrasia (monoclonal gammapathies) and their associated protein abnormalities. As reviewed in reference 1, these syndromes include multiple myeloma and its many clinical and protein varients, macroglobulinemia, “primary” amyloidosis, and the y-, a-, and z-heavy chain diseases (HCDs). In this paper we describe a previously unrecognized form of plasma cell dyscrasia associated with the production of IgGA molecules, y heavy chains and A light chains, all of which are incomplete and presumed to be deleted. An additional unusual feature of the A-chains is the presence of significant amounts of conjugated carbohydrate.