Ineffectiveness of Phenytoin Treatment on IgA-Containing Circulating Immune Complexes in IgA Nephropathy

Ineffectiveness of Phenytoin Treatment on IgA-Containing Circulating Immune Complexes in IgA Nephropathy R. Coppo B. Basolo M.R. Bulzomi G. Piccoli R. Coppo, B. Basolo, M. R. Bulzomi, G. Piccoli, Cattedra di Nefrologia Medica, dell’Università di Torino, Divisione di Nefrologia e Dialisi, Nuova Astanteria Martini, Largo Gottardo 143, I-10153 Torino (Italy) Dear Sir, After the first report [1] indicating that in patients affected with IgA nephropathy, phenytoin selectively decreases serum IgA – especially polymeric IgA – levels, leading to a reduction in the number of episodes of macroscopic hematuria and in some cases a decrease in the amount of IgA deposits, a recent trial reported by Clarkson et al. [2] failed to find any significant influence of this treatment on the clinical and histological course of this nephropathy. Since immunological studies from our group [3] and others [4] in agreement with recent experimental models [5, 6] suggest a primary role for IgA-containing circulating immune complexes (IgAIC) in Berger’s and Henoch-Schönlein’s glomerulonephritis (GN), we would like to comment the data we obtained by monitoring IgAIC detected by a modified conglutinin solidphase assay [3], in two groups of patients: one (3 Berger’s GN and 2 Henoch-Schönlein’s GN) treated with phenytoin (300 mg/day for 8–14 months), and the other (3 Berger’s GN and 2 Henoch-Schönlein’s GN) without any treatment (control group). In the group of patients treated with phenytoin, we observed (table I), as early as 3 months after treatment was started, a significant reduction in mean serum IgA levels (p < 0.05). The IgA concentration decreased by 24.8% after 3 months and by 31.4% at the end of the follow-up. No significant fluctuations were observed in the control group. A slight reduction in mean polymeric IgA values -detected by the reduction-alkylation test [7] – was observed from the beginning to the end of the follow-up (p < O.l), and was particularly evident in 3 of 5 cases who initially showed high values of polymeric IgA. The IgA-containing immune complex levels showed a slight, although not significant (p > O.l), decrease from the beginning to the end of the follow-up in both groups of patients, with and without treatment (table I). No correlation was found between IgA levels and IgAIC values (r0.17, p > O.l). Fig. 1. G.B. ♂ 23 year old, affected with Berger’s GN ( ). After 3 months of phenytoin treatment, total IgA and polymeric IgA decreased, whereas IgAIC increased concomitantly with the appearance of gross hematuria. Z.V. ♂ 19 year old, affected with Henoch-Schönlein’s GN ( ). During phenytoin treatment, IgAIC initially decreased, but rose again concomitantly with gross hematuria even though a decrease in total IgA and polymeric IgA had been obtained. In 2 cases on phenytoin (1 Berger’s GN and 1 Henoch-Schönlein’s GN) gross hematuria was observed: the IgAIC levels were very high, albeit a decrease in total IgA and polymeric IgA was