The role of apoptosis proteins and complement components in the etiopathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.

A Case of Steroid-responsive C1q Nephropathy Presenting as Focal Segmental Glomerulosclerosis / 대한신장학회지

C1q nephropathy is an immune complex glomerulonephritis defined by the presence of mesangial immunoglobins and complement deposits, most notably C1q, and the absence of clinical and laboratory evidence of systemic lupus erythematosus. Most patients with C1q nephropathy present nephrotic-range proteinuria, which has a poor response to steroid. Some patients may experience decreased renal function and progress to end stage renal disease. A 27year-old man presented with proteinuria and decreased mental state. The patient was hypertensive, with a blood pressure of 180/120 mmHg. Serum BUN/creatine was 18/1.8 mg/dL, and urinalysis revealed proteinuria (3+). Brain computed tomography showed right basal ganglial and intraventricular hemorrhage. The patient was treated with craniotomy and hematoma removal, and he also received carvedilol, losartan, nifedipine, and doxazosin for control of BP. Although his mental status recovered and blood pressure was controlled, the patient still showed subnephrotic proteinuria; therefore, renal biopsy was performed. Kidney biopsy showed segmental sclerosis in 3 out of 14 glomeruli, and mesangial C1q immunofluorescence positive staining. Electron microscopic findings revealed electron-dense deposits in the mesangium. The patient was treated with oral prednisolone, and proteinuria was alleviated after 8 weeks and remains in complete remission.

C1q Nephropathy: A Distinct Pathologic Entity

BACKGROUND: C1q nephropathy (C1qN) is a controversial diagnostic entity defined by Jennette and Hipp in 1985. The prevalence is very low and a few large scale studies have been reported. Application of the criteria for clinical diagnostics of C1qN may cause confusion with other glomerulonephropathies, such as minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). In order to clarify the confusion with glomerulonephropathies, we did this study to identify the clinicopathological characteristics and the exact disease entity of C1qN. METHODS: A total of 5,258 kidney biopsies at Kangnam St Mary's Hospital were reviewed. Twenty three cases (0.44%) met the criteria of C1qN. Twenty eight cases showing dominant C1q deposits without electron dense depostis (EDD) grouped as C1q+EDD-, and previously diagnosed typical cases of MCD and FSGS were selected for this study. Four groups were compared to each other with regard to the clinical and pathological aspects of the disease. RESULTS: C1qN patients had an average age of 30.4 years. Eighteen were males and 5 were females. Eighty seven percent had proteinuria and 18% had hematuria. By electron microscopy analysis, 100% had mesangial EDD and 47.8% showed foot process effacement. C1qN had some significant differences compared with C1q+EDD-, MCD and FSGS. CONCLUSIONS: C1qN is clinically and morphologically different from MCD and FSGS. However, additional long term studies are needed to fully define C1qN from other glomerulonephritis with C1q deposits.