THE STUDY OF URINARY SECRETORY IgA

(I). ITS LOCALIZATION IN THE URINARY TRACT

Abstract

The way of immune response is divided into humoral antibody and cell-mediated immunity, the former possesses two factors which are systemic immunity and local immunity. Local immunity, at present, has been mainly studied in the respiratory tract or the gastrointestinal tract. The knowledge about the urinary tract is still meagre. We studied the urinary secretory IgA (SIgA), especially its localization in the urinary tract, for the first step of the study of the urinary local immune systems.
As the detective method for the urinary immunoglobulins and serum SIgA, we used Enzyme-linked Immunosorbent Assay (E. L. I. S. A.) technique using horseradish peroxidase as enzyme for avoiding the inaccuracy and the complexity of Single Radial Immunodiffusion Assay (SRID), in which urine is needed at 100-1, 000 fold concentration for detection. Urinary IgG and IgM were detected with monospecific rabbit antisera in the same way as we did on the serum. Assay of urinary IgA was performed after absorption of the samples with anti SC. Urinary SIgA was detected with anti SC, based upon the result that the values of SIgA with anti SC as antibody were correlated to the values of SIgA using anti SC minus FSC. Serum and urinary albumin, serum IgG, IgM, IgA were measured with SRID. For the localization of SIgA in the tissues, indirect method of enzyme-antibody technique which used peroxidase as enzyme was employed. This technique, compared to fluoresent antibody technique, has some merits; 1). Ordinary light-microscope is able to be used, 2). Specimens can be preserved permanently, 3). It may apply to immune electron microscopy.
The conclusions obtained were as follows;
1) Urinary IgG, IgM, IgA and SIgA values of 18 patients of chance, proteinuria were about 10 fold of 43 healthy controls. The clearance values in IgG, IgM and IgA, which was calculated from serum and urinary values and urine flow rate, were distributed with a similar range to that in albumin. But the value of clearance in SIgA was much higher. SIgA was higher than other immunoglobulins in urinary per serum ratio against albumin. Local production rate in the urinary tract, which was calculated with the formula of (C_Ig.-C_A1b./C_Ig.)×100, was able to be calculated in 6 cases of IgG, 4 of IgM and 1 of IgA. But the rate of SIgA even in the least case was 99.3%. Therefore, we thought that urinary SIgA would be originated entirely from the urinary tract.
2) The distribution of SIgA in the urinary tract was studied by the detection of SIgA using bilateral renal urine, vesical urine and spontaneous urine. There was no laterality between renal urines in secreting SIgA. On the average, in male, SIgA was secreted from kidney or ureter by 6.5%, bladder by 20.6% and urethra by 72.9%. In female, the percentages were 9.7%, 21.4% and 68.9% respectively. The superiority in the urethra in secreting urinary SIgA was evident.
3) The detection of SIgA and bacterial count were done in the saline irrigated small-cutted urethra of a female patient with urethral tumor. The peak levels of SIgA were near the external urethral orifice and bladder neck, and it was low in the mid-urethra. The number of bacteria was on the order of 10³ level at any areas. Therefore, urethral SIgA was not considered to be the natural antibody against these normal flora.
4) Using renal and vesical urine collected every 4 hours from 2 patients (Lt.-U. P. stricture, Idiopathic retroperitoneal fibrosis), secreting circadian rhythm of SIgA was studied. In these four groups, SIgA values had two peaks every 12 hours. Therefore, collection of random urine must be performed cautiously in estimating urinary SIgA.
5) The tissue specimens from urinary tract infections were studied by enzyme-antibody technique. In the renal tissue (basal disease was renal stone), the dark brown spots of SIgA were dispersed in tubular epithelial cells and mesenchyma.