Clinical significance of glomerular IgG4 deposition in primary membranous nephropathy / 中华肾脏病杂志

ABSTRACT

Objective:To analyze the distribution of glomerular immunofluorescence IgG4 subtypes in primary membranous nephropathy, and to explore the relationship between IgG4 deposit intensity and renal pathology, clinical manifestations and prognosis.Methods:All the patients of biopsy-proven primary membranous nephropathy with IgG staining and at least one IgG subtype staining 1+ or higher on capillary loops from September 2015 to April 2017 were retrospectively enrolled. The distribution of IgG4 deposits were analyzed, and the relationship between IgG4 positive intensity and clinical manifestations, pathological indexes and clinical remission was investigated.Results:A total of 250 cases were enrolled, including 157 males (62.8%) and 93 females (37.2%), and age was (54.4 ± 14.6) years. There were 40 patients in IgG4-negative group, and 210 patients in IgG4-positive group. The IgG4-positive group was divided into subgroups as 114 cases of the mild positive subgroup (1+) and 62 cases of the moderate positive subgroup (2+), and 34 cases of the strong positive subgroup (3+, 4+). The IgG4-positive group had higher 24-hour urine protein and higher positive rate of phospholipase A2 receptor staining than those in the negative group (both P<0.05), while the strong positive subgroup had lower serum albumin and higher IgG1 staining than those in the mild positive subgroup (both P<0.05). There was no difference in the ratio of glomerular sclerosis, tubular atrophy, IgG2, IgG3 or other immunofluorescence between the groups. After a median follow-up of 180(122, 209) days, 32 individuals were lost to follow-up. Among the rest 218 patients, 45 patients (20.6%) got complete remission, 104 patients (47.7%) got partial remission, and 69 patients (31.7%) showed no response. For no response as the outcome event, multivariate Cox regression analysis showed that higher IgG4 staining intensity ( HR=1.371, 95% CI 1.068-1.759, P=0.013), male ( HR=1.818, 95% CI 1.028-3.214, P=0.040), higher 24-hour urine protein level ( HR=1.108, 95% CI 1.003-1.225, P=0.043) were independent risk factors for disease remission. Conclusions:The glomerular IgG4 positivity and intensity are related to the severity of primary membranous nephropathy. The glomerular IgG4 deposit degree may be an effective prognostic marker for the treatment response of primary membranous nephropathy.