Clinical Significance of Polymeric and Monomeric IgA Complexes in Patients With IgA Nephropathy Paloma Hernando, MD, Jesus Egido, MD, Rosario de Nicolas, SS, and Jaime Sancho, PhD • IgA nephropathy is currently considered an immune complex (IC) disease. However, though several groups have demonstrated the presence of IgA-IC in the sera of patients by various techniques, a correlation with clinical activity of the nephropathy has not always been found. Since these assays detect (simultaneously) polymeric and monomeric IgA-IC, the pathogenicity of these two classes of complexes could not be established. In this work, we have studied in 66 patients with IgA nephropathy the existence and significance of such IC, by means of a tech- nique described in our laboratory, based on the specific binding of secretory component for polymeric IgA. Furthermore, IgG-ICs were also determined by the standard Raji cell assay in ELISA. The prevalence of these complexes was as follows: Multimeric (polymeric and monomeric) IgA-ICs were detected in 55% of 66 patients studied, polymeric IgA-ICs in 30%, monomeric IgA-ICs in 39%, and IgG-ICs in 46%. The intermittency of all these complexes was clearly noted in sequential examinations. A significant correlation (P < .025) with hematuria was only found with polymeric IgA-IC, but not with multimeric IgA-IC, monomeric IgA-IC, or IgG-IC. Polymeric IgA-ICs were more frequently observed at the initial phases of the disease. Analytical ultracentrifugation showed that polymeric IgA-IC was of larger size than monomeric IgA-IC. The major pathogenicity of polymeric IgA-IC is in agreement with the finding of this immunoglobulin at the mesangial level in patients and animals with IgA ne- phropathy. © 1986 by the National Kidney Foundation, Inc. INDEX WORDS: IgA nephropathy; IgA immune complexes; polymeric IgA immune complexes; hematuria. T HE MOST frequent glomerular disease found in many countries is IgA nephropathy. 1-3 Al- though its pathogenesis is not completely under- stood, the constant presence of IgA, and some- times C3, in a granular pattern in the glomerular mesangium, as well as the recurrence of IgA de- posits in renal allografts, strongly suggests mesan- gial deposition of IgA immune complexes (ICs). Our group initially showed the presence of such complexes in the sera of these patients by sucrose density gradient ultracentrifugation at physiologic and acid pH values. 4 However, the practicallimi- tation of this laborious assay to study a large num- ber of patients was evident. During the last few years, several groups have demonstrated, in patients with IgA nephropathy, the presence of circulating IgA-IC by different techniques, eg, Raji cell assay, anti-IgA inhibition From the Servicio de Nefrologla, Fundacion Jimfmez Dlaz, Universidad Autonoma, Madrid. Supported by grants from Instituto Nacional de la Salud, Comision Asesora de Investigacion Cientijica and Fundacion Inigo Alvarez de Toledo. Address reprint requests to Jesus Egido, MD, Servicio de Nefrologla, Fundacion Jimenez Dlaz, Av Reyes Catolicos 2, 28040 Madrid, Spain. © 1986 by the National Kidney Foundation, Inc. 0272-6386/86/0806-0004$03.00/0 assay, or other less specific methods. 1.5 All these assays, however, do not distinguish polymeric IgA-IC from monomeric IgA-IC. Taking into ac- count that polymeric IgA is found in the mesan- gium of these patients,6 the existence of a tech- nique permitting the study of these two classes of ICs seemed necessary. Based on the specific bind- ing of the secretory component (SC) for polymeric IgA, we developed a method that enabled us to differentiate both classes of IC.7 Following our preliminary report on a relatively small number of subjects,8 we now present the results on 66 pa- tients with primary IgA nephropathy. The more important data afforded by this study reflect that while either polymeric or monomeric IgA-IC can be found in these patients, only those containing polymeric IgA were significantly correlated with the clinical activity of the disease, as defined by the presence of hematuria. PATIENTS AND METHODS Patients Sixty-six patients with IgA nephropathy were studied (age range 11 to 54 years, mean age 23.5 ± 10 years); 37 were male and 29 were female. The diagnosis was based on the pres- ence of IgA in the glomerular mesangium with or without C3 and other immunoglobulins. Patients with clinical or biochemi- cal evidence of liver disease, systemic lupus erythematosus, 410 American Journal of Kidney Diseases, Vol VIII, No 6 (December), 1986: pp 410-416