title: Evaluation of diagnostic criteria for IgG4-related tubulointerstitial nephritis.
abstract: BACKGROUND
  IgG4-TIN is the most common pattern of renal involvement in IgG4-related disease. There are several proposed diagnostic criteria of IgG4-TIN recently. Two of them proposed by the Mayo Clinic and JSN are predominant. However, histopathological criteria of the number of IgG4+ plasma cells and several histological features are still under discussion due to low amount of tissue in renal biopsy specimens and low frequency of this kind of specimens. We aimed to screen IgG4-TIN on archived renal biopsy samples and evaluated the application of two proposed diagnostic criteria.
  
  
  METHODS
  We selected 480 interstitial inflammation samples for light and electron microscopy and immunohistochemistry of CD138, IgG and IgG4 test. The Mayo Clinic proposed criteria diagnosed high-probability IgG4-TIN and JSN criteria confirmed IgG4-TIN.
  
  
  RESULTS
  Twelve high-probability IgG4-TIN were screened by histology, imaging, serology and other organ involvement according to the Mayo Clinic proposed criteria. The previous principal pathological diagnoses were IgAN (n=4), CreGN (n=4), tubulointerstitial nephritis (n=3) and LN (n=1). Three cases showed storiform fibrosis and a bird's eye pattern. The distribution of IgG4+ plasma cells was focal, multifocal or diffuse, with a mixed mild, moderate or strong stainingpattern. Their treatment and clinical outcomes varied depending on different levels of proteinuria, serum creatinine, eGFR and original glomerular disease presentation. Therefore, we applied strict histological criteria of storiform fibrosis and evenly distributed IgG4+ plasma cells by JSN to confirm typical IgG4-TIN. Two cases were finally diagnosed as real IgG4-TIN. One was previously diagnosed as idiopathic interstitial nephritis with rapid response to corticosteroid therapy. The other was CreGN with immune complex deposits, which had poor outcome and long-term hemodialysis.
  
  
  CONCLUSIONS
  IgG4-TIN might present concurrently with glomerular disease. The proposed criteria by the Mayo Clinic is flexible, sensitive, and superior in the identification of early-stage or atypical IgG4-TIN, with enhanced risk of misdiagnosis as compared to the proposed criteria by JSN, which is stricter, more specific, and might overlook early-stage or atypical IgG4-TIN. We propose a new set of criteria to improve pathologist-derived diagnosis.
authors.affiliation: Department of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou hospital of traditional Chinese medicine, Hangzhou, 310007, China. tangsunshine1981168@sina.com.
authors.forename: Xuanli
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou hospital of traditional Chinese medicine, Hangzhou, 310007, China. zhubing@hotmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Zhejiang Academy of Medical Science, Hangzhou, 310007, China. chen-ri-ping@163.com.
authors.forename: Riping
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou hospital of traditional Chinese medicine, Hangzhou, 310007, China. sbsys@sina.cn.
authors.forename: Yunqin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou hospital of traditional Chinese medicine, Hangzhou, 310007, China. zyhbaby@126.com.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou hospital of traditional Chinese medicine, Hangzhou, 310007, China. zhuxiaolinghz@126.com.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou hospital of traditional Chinese medicine, Hangzhou, 310007, China. chy_2014@sina.cn.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Nephrology (Key laboratory of Zhejiang province, management of kidney disease), Hangzhou hospital of traditional Chinese medicine, Hangzhou, 310007, China. yc0822@126.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003937:Diagnosis, Differential; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis* / Q000097:blood; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D053668:Syndecan-1 / Q000032:analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; C508241:SDC1 protein, human; D053668:Syndecan-1