IgM,Not 7S-IgM,as Cause of Increased Serum IgM Concentrations in Goiter Patients

Abstract

Circulating concentrations of immunoglobulin-M (IgM) are increased in about half of patients with endemic or sporadic nontoxic goiter (1). In the single radial immunodiffusion technique used to test those serums (2), the diameter of the precipitin ring developed against the anti-IgM serum in the agar is proportional to the logarithm of the amount of IgM in the well.

Our attention has been called by Dr. William D. Terry of the National Institutes of Health to the possibility that a 7S-subfraction of IgM first identified in some patients with systemic lupus erythematosus (3), termed 7S-IgM, might produce large rings in the agar plates because of the more rapid spread than that of the intact IgM antibody. As a result, spuriously high estimates of IgM concentrations would be made. To exclude the presence of 7S-IgM, therefore, we have reexamined several serums previously determined to have elevated IgM concentrations.

Nine serums were tested: 4 from patients with endemic nontoxic nodular goiter [Patients 1, 2, 4 and 5 (Table I)]; 2 with sporadic goiter (Patients 6 and 7); and 3 with toxic diffuse goiter (Patients 3, 8 and 9). Serum IgM concentrations have been reported by Mahaux et al. to be increased (4) in patients with active Class 2 through 6 eye changes of Graves' disease. (5).

To distinguish 7S-IgM from intact IgM, sucrose density gradient ultracentrifugation (6) and Sephadex G-200 column chromatography were employed. In the former procedure (6) effluent fractions were collected and protein and IgM concentrations of every second tube through tube 14 determined, using 0.02 cc of the effluent fractions by Folin method (7). The tubes were then combined into three fractions. The first fraction contained only 19S material, the third fraction 7S material, and the second fraction a mixture of the two.