Significance of IgG4 Immunostaining in Plasma Cell-Rich Tubulointerstitial Nephritis (TIN).
Yassaman Raissian, Samih H Nasr, Christopher P Larsen, Mary E Fidler, Sanjeev Sethi, Ami Bhalodia, Lynn D Cornell. Mayo Clinic, Rochester, MN; Nephropath, Little Rock, AR; Univ of Louisiana, Shreveport
Background: A number of conditions may cause TIN. IgG4 staining has been proposed as a tool to identify TIN as part of IgG4-related systemic disease(IgG4-RSD), but the sensitivity and specificity of IgG4 staining has not been established.
Design: A database search was performed for all cases within one year(2007) with a final diagnosis of TIN, including cases with glomerular disease; causes of TIN were based on clinical and laboratory data. Light microscopy slides of TIN cases were reviewed for increased plasma cells, defined as >5 cells/40x field in ≥3 fields. Cases with increased plasma cells were stained for IgG4 by immunohistochemistry. For comparison, IgG4 staining was also done on TIN cases in patients with clinical features suspicious for IgG4-RSD(n=23), TIN in patients with a history of pancreatitis(n=17), pauci-immune crescentic glomerulonephritis(GN)(n=14), Sjogren TIN(n=14), drug-related(n=5), chronic pyelonephritis(n=2), and unknown or autoimmune cases(n=4). IgG4 stains were graded in the most concentrated area per 40x field as: no increase <5 cells, mild 5-10, moderate 11-30 and marked >30.
Results: Within the given year, 414 cases of TIN were found including 167 cases with associated non-diabetic glomerular disease. Of these, 83/414(20%) had at least moderate increase in plasma cells, with etiology as follows: 25% drug effect, 21% unknown, 20% associated with pauci-immune GN, 14% with other glomerular disease(immune-mediated crescentic GN,FSGS,diabetes), 10% autoimmune disease, 2% pyelonephritis, 2% IgG4-RSD, 1% oxalate nephropathy. 15/83(18%) showed moderate or marked increase in IgG4+ plasma cells; these cases were pauci-immune GN(n=7), TIN due to drug(n=3), other glomerular disease(n=2), pyelonephritis(n=1), and IgG4-RSD(n=1).
In the comparison groups, 23/23(100%) of the IgG4-RSD showed moderate to marked increase in IgG4+ cells, 6/24(25%) cases of pauci-immune GN, 1/14(7%) Sjogren TIN, and 0/17(0%) TIN in patients with a history of pancreatitis, 1/2(50%) with pyelonephritis, and 0/4(0%) TIN of unknown etiology showed increased IgG4+ cells.
In total, excluding IgG4-RSD and pauci-immune GN, 9/107(8%) of TIN studied showed at least moderate increase in IgG4+ plasma cells. If pauci-immune GN is excluded, the IgG4 stain has a sensitivity of 100% and a specificity of 92% for TIN as part of IgG4-RSD.
Conclusions: IgG4 is a sensitive and specific marker for diagnosis of TIN as part of IgG4-RSD. Increased IgG4+ cells may also be seen in pauci-immune crescentic GN; rare other TIN cases may show increased IgG4+ cells.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 258, Wednesday Afternoon