J Pathol Transl Med.  2016 Jan;50(1):26-36. 10.4132/jptm.2015.11.09.

Overview of IgG4-Related Tubulointerstitial Nephritis and Its Mimickers

• Jeong HJ
• Shin SJ
• Lim BJ

• KMID: 2211398
• DOI: http://doi.org/10.4132/jptm.2015.11.09

Abstract

Tubulointerstitial nephritis (TIN) is the most common form of renal involvement in IgG4-related disease. It is characterized by a dominant infiltrate of IgG4-positive plasma cells in the interstitium and storiform fibrosis. Demonstration of IgG4-positive plasma cells is essential for diagnosis, but the number of IgG4-positive cells and the ratio of IgG4-positive/IgG-positive plasma cells may vary from case to case and depending on the methods of tissue sampling even in the same case. IgG4-positive plasma cells can be seen in TIN associated with systemic lupus erythematosus, Sjogren syndrome, or anti-neutrophil cytoplasmic antibody-associated vasculitis, which further add diagnostic confusion and difficulties. To have a more clear view of IgG4-TIN and to delineate differential points from other TIN with IgG4-positive plasma cell infiltrates, clinical and histological features of IgG4-TIN and its mimickers were reviewed. In the rear part, cases suggesting overlap of IgG4-TIN and its mimickers and glomerulonephritis associated with IgG4-TIN were briefly described.

Keyword

IgG4-related disease; Lupus nephritis; Sjogren's syndrome; Anti-neutrophil cytoplasmic antibody-associated vasculitis; Glomerulonephritis, membranous

MeSH Terms

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Diagnosis
Fibrosis
Glomerulonephritis
Glomerulonephritis, Membranous
Lupus Erythematosus, Systemic
Lupus Nephritis
Nephritis, Interstitial*
Plasma Cells
Sjogren's Syndrome
Tin
Tin

Figure

• 

  Fig. 1. Tubulointerstitial nephritis in IgG4-related disease. (A, B) At lower power, interstitial fibrosis is severe and shows a focal streaming pattern with mixed inflammatory infiltration of lymphocytes and plasma cells (A, periodic-acid Schiff ×100; B, Masson trichrome ×100). (C) In some cases, eosinophil infiltration may be prominent (hematoxylin-eosin. ×400). (D) Many IgG4-positive plasma cells are present in the interstitium (IgG4, ×200). (E) On electron microscopy, fine granular electron-dense deposits are present in the interstitium (×15,000). (F) Contrast-enhanced computed tomography shows patchy multiple round or wedge-shaped parenchymal low-density lesions in both kidneys.

• 

  Fig. 2. Tubulointerstitial nephritis in lupus nephritis. Granular electron-dense deposits are present in the tubular basement membrane (×3,000).

• 

  Fig. 3. Tubulointerstitial nephritis in Sjögren syndrome. (A) Lymphoplasmacytic infiltrate is present in the interstitium associated with moderate tubulitis (hematoxylin-eosin, ×200). (B) Interstitium is widened by edema and cellular infiltrate without glomerular lesions (Masson trichrome, ×100).

• 

  Fig. 4. Membranous nephropathy associated with IgG4-TIN. (A) Glomerular basement membrane is thickened with occasional spikes (periodic acid-Schiff, ×200). (B) Granular staining of IgG is present along the peripheral capillary walls (IgG, ×200). (C) Subepithelial electron-dense deposits are seen (×3,000).

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