IgA deficiency and membranous glomerulonephritis

Abstract

Sirs, I read with interest the article in this journal entitled “IgA deficiency and membranous glomerulonephritis presenting as nephrotic syndrome” by Kawasaki et al. [1]. The authors suggested that an increased level of circulating immune complexes was involved in the pathogenesis of membranous glomerulonephritis (MGN) in patients with IgA deficiency [1]. However, the renal biopsy of the patient described by Kawasaki et al. demonstrated diffuse and global thickening of the glomerular capillary walls in the absence of any mesangial changes, mesangial deposition of immunoglobulin or complements or mesangial electron-dense deposits, findings that are compatible with idiopathic MGN [2]. Selective IgA deficiency-associated glomerulonephritis is rare, and only 19 patients have been reported [1, 3]. Renal biopsy demonstrated mesangial proliferation in the majority of patients with IgA deficiency and glomerulonephritis, thereby suggesting a major role of circulating immune complexes on the development of glomerulonephritis in patients with IgA deficiency [3]. However, the renal biopsies of some patients with IgA deficiency exhibited minimal change disease and idiopathic MGN, without evidence of mesangial proliferation, and these conditions are likely to be unrelated to circulating immune complexes [3]. Circulating immune complexes are present in 50–60% of patients with IgA deficiency, and their formation is probably the result of defective antigen exclusion at the level of the mucosa [4]. A failure to exclude microbial antigens in IgA deficiency also results in chronic immunological activation and autoimmune disease, including systemic lupus erythematosus and rheumatoid arthritis [5]. Although the precise pathogenic mechanisms for the development of human idiopathic MGN remain unclear, there is considerable experimental support for subepithelial in situ immune complex formation [2, 6]. On the other hand, because secondary MGN is caused by circulating immune complexes, immune complexes can deposit in the mesangium as well as in the subepithelial space [2, 6]. Thus, secondary MGN usually exhibits mesangial proliferation and mesangial electron-dense deposition [2, 7]. Therefore, the MGN affecting the patient described by Kawasaki et al. is more likely to result from in situ immune complex formation caused by chronic immunological activation or cryptic autoimmune disease than from circulating immune complexes. Interestingly, Yewdall et al. described a patient with IgA deficiency and idiopathic MGN who later developed systemic lupus erythematosus [5]. This reinforces the requirement for long-term follow-up in order to determine whether or not the patient reported by Kawasaki et al. develops autoimmune diseases in the future.