Abstract: TH-PO503

Tubulointerstitial Nephritis with IgM-Positive Plasma Cells

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

  • Takahashi, Naoki, University of Fukui, Fukui, Japan
  • Fukushima, Sachiko, University of Fukui, Fukui, Japan
  • Yokoi, Seiji, University of Fukui, Fukui, Japan
  • Mikami, Daisuke, University of Fukui, Fukui, Japan
  • Kimura, Hideki, University of Fukui, Fukui, Japan
  • Kasuno, Kenji, University of Fukui, Fukui, Japan
  • Narita, Ichiei, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Iwano, Masayuki, University of Fukui, Fukui, Japan
  • Saeki, Takako, Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
  • Komatsuda, Atsushi, Akita University School of Medicine, Akita, Japan
  • Samejima, Ken-ichi, Nara Medical University, Kashihara, Japan
  • Nishikawa, Yudai, University of Fukui, Fukui, Japan
  • Nishimori, Kazuhisa, University of Fukui, Fukui, Japan
  • Morita, Sayu, University of Fukui, Fukui, Japan
  • Kobayashi, Mamiko, University of Fukui, Fukui, Japan
  • Morikawa, Yukie, University of Fukui, Fukui, Japan
Background

Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis (TIN). Routine immunofluorescence of frozen sections is currently considered the gold standard for detection of immune deposits; however, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium. It was thought that CD138-positive mature plasma cells secrete IgG, and the occurrence of TIN with CD138-positive plasma cells secreting IgM has rarely been reported. We recently discovered a case of TIN showing IgM-positive plasma cell (IgMPC) accumulation within the interstitium (Clin Nephrol 74: 74-80, 2010).

Methods

To further explore the morphological and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven TIN and high serum IgM levels.

Results

In 13 of those patients, the pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and co-localized IgMPCs as well as tubulitis in the proximal tubules and collecting ducts with CD3-positive T lymphocytes. The number of infiltrating IgMPCs per high-power field from 13 patients was significantly higher than from control patients with other forms of TIN chosen as controls for staining (n=44) (p<0.001). Receiver operating characteristic (ROC) curve analysis revealed that optimal predictive cutoff number for infiltrating IgMPCs was 13 per high-power field, with an area under the ROC curve of 0.99 (p<0.0001). The sensitivity and specificity were 100% and 93.2%, respectively. In addition, levels of H+-ATPase, H+, K+-ATPase and HCO3--Cl- anion exchanger in the collecting ducts were significantly lower in 13 patients than in control patients with TIN. The clinical findings with these patients were a high prevalence of distal RTA (100%), Fanconi syndrome (92%) and anti-mitochondrial antibodies (82%).

Conclusion

We propose to designate this group of cases, which have a common histological and clinical form, as “IgM-positive plasma cell-tubulointerstitial nephritis” (IgMPC-TIN).

Funding

  • Government Support - Non-U.S.