IgG4-related Disease:Clinical Features And Relationship With Mast Cells

Objective: This investigation is aimed to explore the clinical characteristics of Ig G4-related disease in Chinese by detailed clinicopathological and laboratory assessments. And to investigate the causes of renal failure in patients with Ig G4-related retroperitoneal fibrosis, steroid therapeutic effect, and to explore the factors affecting the prognosis of renal function. To explore the role of mast cells in the pathogenesis of Ig G4-RD.Method:1. The baseline features of the patients with biopsy-proven disease were reviewed. The diagnosis was confirmed by pathology review according to consensus diagnostic criteria and clinicopathologic correlation. Disease activity and damage were assessed by the Ig G4-RD Responder Index(RI).2. Ten cases with Ig G4-RD involving the superficial lymph nodes were enrolled, while 10 cases of normal superficial lymph nodes tissue were selected as control. The infiltration of mast cells in superficial lymph tissue were detected respectively by toluidine blue staining and immunohistochemistry of c-kit. And the correlation between mast cell count and the clinical parameters of Ig G4-RD(serum Ig G4 concentration, Ig G, Ig E, serum complement C3, ESR, CRP, Ig G4-RD RI) were analyzed.Results:1. Thirty(83.3%) of the patients were male, while six were female, the onset age was 65.1. All of the 36 patients had active disease, 77.7% had elevated serum Ig G4 concentrations and 44.4% had hypocomplementemia. Patients with elevated serum Ig G4 had a higher RI, a greater number of organs involved(P<0.01 for all comparisons). The correlation between serum Ig G4 level and RI(p<0.001,R=0.737) was stronger than Ig G, ESR, CRP and serum completment levels. Hypocomplementemia was common among Ig G4-RD patients with kidney disease. 28 patients received glucocorticoids therapy, and had lower RI and serum Ig G4 concentration after therapy(P<0.01).2. All of the 10 patients were male, the onset age was 64.2±10.04 years. Nine patients had elevated serum Ig G4 concentrations, 9 had anemia, and 2 had positivity of antinuclear antibodies. Five patients presented with acute renal failure(ARF), and other 5 cases showed ARF on chronic kidney disease(A on C) at diagnosis. One case had Ig G4-TIN confirmed by renal biopsy. Six patients underwent hemodialysis treatment. SCr returned to normal in five patients with ARF and 1 case of A on C, while the SCr level of the rest 4 patients of A on C returned to baseline levels after therapy. SCr after steroid therapy was significantly lower than SCr before treatment(P <0.05). Six patients stopped hemodialysis therapy. All of the patients developed into chronic renal failure(CRF) had a history of CKD at diagnosis, the longer period of persistently elevated SCr, thinner total renal parenchyma thickness, and had a continuous elevated serum Ig G4 after steroid therapy, compared with those SCr back to normal(P<0.05).3. The mast cell count of the superficial lymph node tissue in the Ig G4-RD group was significantly more than in the control(39±16.2 vs 7(0-40),P=0.002). The mast cell count in lymph node tissue of Ig G4-RD patients had significantly correlation with Ig E concentrations(P<0.001, r=0.938, R2=0.880).Conclusions:1. Both Ig G4-RD RI and Ig G4 concentration might be regarded as assessment markers of disease activity and therapeutic effect. The diagnosis of Ig G4 related disease should be supported by histopathology and clinical features.2. The main cause of renal failure is obstructive nephropathy caused by retroperitoneal fibrosis. Recovery and prognosis of renal function primarily related to the timing of diagnosis and treatment. The history of CKD, the period of elevated SCr, thinner total renal parenchyma thickness before steroid therapy, and persistently elevated serum Ig G4 concentrations after steroid therapy may indicate poor prognosis of renal function.3. Mast cells possibly have an important role in disease pathogenesis.