Plasma exchange and rituximab treatments in primary membranous nephropathy combined with crescentic glomerulonephritis: A case report.

RATIONALE: Crescent formation is rare in primary membranous nephropathy (MN). Anti-phospholipase A2 receptor (PLA2R) antibodies are detectable in these patients. The mechanism and treatments are unknown. PATIENT CONCERNS: A 72-year-old female patient who presented with nephrotic syndrome, hematuria, and rapidly progressive kidney dysfunction. DIAGNOSES: Kidney biopsy was performed and the diagnosis was MN in combination with crescentic glomerulonephritis. Circulating anti-PLA2R IgG3 and IgG4 were detected of high level. INTERVENTIONS: The patient received plasma exchange and rituximab besides corticosteroids. OUTCOMES: The patient achieved complete remission of proteinuria and recovery of kidney function after the clearance of anti-PLA2R antibodies. LESSON: This case suggests a pathogenic role of anti-PLA2R antibodies in the mechanism of crescent formation in MN, which may need intensive therapy to eliminate the antibodies quickly.

T cell responses to peptides of Goodpasture autoantigen in patients with anti-glomerular basement membrane disease.

AIM: Cell-mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti-glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti-GBM patients, aiming to identify the epitopes and their clinical significance. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti-GBM disease. Twenty-four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1. PBMC response to each peptide was detected by proliferation assay. Their associations with clinical features were further analyzed. RESULTS: Peripheral blood mononuclear cells proliferative responses to linear peptides on α3(IV)NC1 could be detected in all patients. Five major epitopes were identified as stimulatory in over half of the patients: α3(IV)NC1127-148 (P14) (69.2%), α3(IV)NC1159-178 (77.8%), α3(IV)NC1179-198 (55.6%), α3(IV)NC1189-208 (P19) (75.0%) and α3(IV)NC1141-154 (57.1%). P14 and P19 were highly recognized in patients comparing with healthy controls (69.2% vs. 0.0%, P = 0.011; 75.0% vs. 0.0%, P = 0.021, respectively). CONCLUSION: T cell proliferation to linear epitopes was detected in human anti-GBM disease. α3127-148 was a mutual T and B cell epitope, implying its initial role in epitope spreading process.

Anti-glomerular basement membrane disease: outcomes of different therapeutic regimens in a large single-center Chinese cohort study.

Anti-glomerular basement membrane (GBM) disease usually presents with rapidly progressive glomerulonephritis accompanied by pulmonary hemorrhage. The low incidence and fulminant course of disease preclude a large randomized controlled study to define the benefits of any given therapy. We conducted a retrospective survey of 221 consecutive patients seen from 1998 to 2008 in our hospital, and report here the patient and renal survival and the risk factors affecting the outcomes. Considering the similar clinical features of the patients, we could compare the effects of 3 different treatment regimens: 1) combination therapy of plasmapheresis and immunosuppression, 2) steroids and cytotoxic agents, and 3) steroids alone.The patient and renal survival rates were 72.7% and 25.0%, respectively, at 1 year after disease presentation. The serum level of anti-GBM antibodies (increased by 20 U/mL; hazard ratio [HR], 1.16; p = 0.009) and the presentation of positive antineutrophil cytoplasmic antibodies (ANCA) (HR, 2.18; p = 0.028) were independent predictors for patient death. The serum creatinine at presentation (doubling from 1.5 mg/dL; HR, 2.07; p < 0.001) was an independent predictor for renal failure.The combination therapy of plasmapheresis plus corticosteroids and cyclophosphamide had an overall beneficial effect on both patient survival (HR for patient mortality, 0.31; p = 0.001) and renal survival (HR for renal failure, 0.60; p = 0.032), particularly patient survival for those with Goodpasture syndrome (HR for patient mortality, 0.29; p = 0.004) and renal survival for those with anti-GBM nephritis with initial serum creatinine over 6.8 mg/dL (HR for renal failure, 0.52; p = 0.014). The treatment with corticosteroids plus cyclophosphamide was found not to improve the renal outcome of disease (p = 0.73). In conclusion, the combination therapy was preferred for patients with anti-GBM disease, especially those with pulmonary hemorrhage or severe renal damage. Early diagnosis was crucial to improving outcomes.