A paraprotein IgA1 occurring in serum, urine, and cerebrospinal fluid (CSF): immunochemical and idiotypic evidence of synthesis in situ by the central nervous system (CNS).

A patient affected with multiple myeloma displayed in the serum, urine, and cerebrospinal fluid a paraprotein with identical electrophoretic mobility. The paraprotein, which was polymeric, appeared in the serum and cerebrospinal fluid mainly as the dimer and tetramer, whereas in the urine the tetramer was predominant. The myeloma protein, identified as an IgA1 kappa, was isolated from the serum and urine and submitted to structural analysis. For reasons of scarcity of material, it was decided to approach the structure of the cerebrospinal fluid paraprotein by means of antiidiotypic antiserum. Complete idiotypic identity between, on the one hand, cerebrospinal fluid and, on the other hand, IgA1 isolated from serum and urine and F(ab)2 alpha derived from serum IgA1 was observed. Adsorption experiments confirmed the idiotypic identity among the three biological fluids. Although the blood-brain barrier of the patient was only slightly disturbed, IgA polymers of MW varying from approximately 280,000 to approximately 840,000 appeared in the cerebrospinal fluid. Consequently the results are good evidence for synthesis within the central nervous system by subsequent generations of a malignant B-cell line which invaded the central nervous system.