Shift of C3 deposition from localization in the glomerulus into the tubulo-interstitial compartment in the absence of secreted IgM in immune complex glomerulonephritis

Abstract

SummaryThe role of secretory IgM in protecting kidney tissue from immune complex glomerulonephritis induced by 4 mg horse spleen apoferritin and 0·05 mg lipopolysaccharide has been investigated in mutant mice in which B cells do not secrete IgM, but are capable of expressing surface IgM and IgD and secreting other Ig isotypes. Glomerular size, number of glomeruli per crosssection, glomerular cellularity and urine content of protein and creatinine was comparable in treated secreted IgM (sIgM)-deficient and wild-type mice. Assessment of urinary proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed a 30 kDa low molecular weight protein in treated sIgM-deficient animals only, reflecting dysfunction of proximal tubules. A shift of bound C3 from glomeruli to the tubulo-interstitial compartment in sIgM-deficient mice also suggests tubulo-interstitial damage. In contrast, local C3 synthesis within the kidney tissue did not differ between the two treated groups. Apoptosis physiologically present to maintain kidney cell homeostasis was increased slightly in treated wild-type mice. These results indicate that secretory IgM can protect the tubulo-interstitial compartment from immune complex-induced damage without having an effect on the glomerulus.

Discrepancies in glomerular and tubulointerstitial/vascular immune complex IgG subclasses in lupus nephritis

“…13 Rare case reports have demonstrated predominant or isolated tubulointerstitial lesions with minimal glomerular abnormalities in patients with systemic lupus erythematosus (SLE), 14 suggesting that glomerular and TBM immune complex formation may be separate events with different triggers. 15,16 Yu et al and Hsieh et al have demonstrated tubulointerstitial lesions including inflammation, fibrosis, and atrophy to be significant independent risk factors for renal outcome in lupus nephritis, 17,18 therefore this is an important area for further studies.…”

IgM Promotes the Clearance of Small Particles and Apoptotic Microparticles by Macrophages

“…Most of these studies focused on understanding the role of complement activation on IgM-mediated late apoptotic cell clearance [13], [18], [20], [21], [22], [23], [24], [25]. Other in vivo studies show that IgM can protect immune complex-mediated damage in specific tissues [26], [27]. Notably, similar to secretory IgA, IgM can reach mucosal surfaces independently of other complement proteins by Th17 regulated transcytosis [9], [28], [29].…”

Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome, Two New Cases and Review of the Literature

“…Our second patient showed a perivascular C3 deposition without vasculitis lesions; peritubular capillary alteration or glomerular deposition, which is a rare case since only 15% showed positive staining [19]. C3 complement component contributes to interstitial injury more than to glomerular lesions, this is due to the fact that Kidney tissue is particularly vulnerable to complementmediated damage due to the low expression of complement regulatory proteins on glomerular and tubular cells [28]. Thus, this deposition argues in favor of an immune-mediated renal diseases and so reinforce the hypothesis of autoimmune origin of TINU syndrome.…”

“…It has been reported in identical twins (boys or girls) and two pairs of sisters so far [27][28][29] and two generations of the same family [16] and no reports of geographic clustering of TINU syndrome cases [19,30]. This fact argues against either environmental or genetic factors as dominant influences in the pathogenesis of the disease [19].…”