The Clinical And Pathological Characteristics Of IgG4 Related Tubulointerstitial Nephritis

Background:Ig G4-TIN is the most common manifestation of Ig G4-related disease when involved kidney.Currently,both of the diagnostic criteria proposed by ASN and JSN have international influences and been applied in clinic practice.Due to the low incidence of such disease,as well as the low amount of tissue in renal biopsy specimens,the criteria of histopathologic characteristics applied in diagnosis still cannot be unified.This study reviewed and analyzed Ig G4-TIN cases of renal biopsy specimens collected in recent years,expecting to reveal the clinical and pathological characteristics of this disease and make an evaluation of the two diagnostic criteria.Methods:We enrolled 175 cases diagnosed by light microscopy as tubulointerstitial nephritis from 2009 to 2015 in Ruijin Hospital,carrying out Ig G4 IHC test on these cases,integrating their clinic,laboratorial and pathological data.And we chose the ASN criteria as main diagnosed criteria,compare with the JSN criteria.Results:Thirteen cases were diagnosed as IgG4-TIN,combined with renal histology,serology,imaging and other extra renal involvement,according to the ASN criteria.The median age of 13 cases was 58(20 ~ 72)years old,the ratio between male and female was 10:3.Level of proteinuria in 10/13 cases(76.9%)was < 3.5g/24 h.All cases had renal insufficiency,e GFR in 12/13 cases(92.3%)was <60ml/min/1.73m2.Anemia was found in 11/13(84.6%)cases.The ratio of hyperglobulinemia of Ig G,Ig G4 and Ig E was 61.5%?85.7% and 53.8% respectively,significantly higher than that of non Ig G4 related tubularinterstitial nephritis(P < 0.05).12/13 cases(92.3%)of Ig G4-TIN had renal related imaging changes.10/13(76.9%)presented extra-renal organ involvement,the median number of affected organ was 1(0 ~ 3).Moreover,two patients had P-ANCA/MPO-ANCA positive,one patient had anti-SSA/SSB antibodies positive,one patient had haemorrhagic fever antibody positive,and one patient had a history of rheumatoid arthritis.As pathological characteristics,lymphocytes and Ig G4 positive plasma cells(> 10 / HPF)infiltration in the interstitum was observed in all 13 cases,among which 9 cases(69.2%)present significant Ig G4 positive plasma cell(> 30 / HPF)infiltration.3/13 cases had characteristic storiform fibrosis or bird's-eye pattern,which were not detected in non Ig G4-TIN.46.2% of the specimens had more eosinophil infiltration,but the ratio of eosinophil infiltration had no statistical difference between Ig G4-TIN and non Ig G4-TIN(P=0.401).In 13 cases of Ig G4-TIN,the higher proportion of severe fibrosis and the renal tubular epithelial cell necrosis were observed than in the non Ig G4-TIN and had statistic significance(P=0.002,P=0.037).Electron dense deposits were observed in the glomerular basement membrane and epithelial side by electron microscope in 1sepecimen,which was similar as that observed in membranous nephropathy.None of 13 cases had electron dense deposition in tubular basement membrane.3/13(23.1%)cases of Ig G4-TIN were combined with glomerular lesions,accompanying nephrotic syndrome in clinical manifestation,such as diabetic nephropathy,focal segmental glomerulosclerosis,and focal segmental endocapillary proliferative glomerulonephritis.Comparing two kinds of diagnostic criteria,the ASN criteria were slack and sensitive,while the JSN criteria was much more strict and distinctive,which may result in missed diagnosis.Nine patients got corticosteroid therapy combined with immunosuppressant or not,and the significant decline of 24 h urinary protein and serum creatinine were detected(P=0.005,P=0.026).Conclusions:IgG4-TIN occurred in older men commonly,be characterized by low to medium amount of proteinuria,anemia and renal insufficiency.The elevated levels of serum lg G,Ig G4,and Ig E could indicate the presence of Ig G4-TIN.Attentions should be paid to this disease especially when the imaging changes were found and the extra-renal organs were involved.In terms of pathology,distinctive storiform fibrosis and bird's-eye pattern had high specificity to diagnosis,but lack of sensibility.Some patients were combined with glomerular lesions.Both two influential diagnostic criteria had advantages and disadvantages respectively.Combining both two criteria may make the diagnosis more effectively and precisely.Corticosteroid was the preferred treatment,combining the utilization of immunosuppressant or not,which would be beneficial to the recovery of renal function and improvement of prognosis.