title: Pathogenetic features of severe segmental lupus nephritis.
abstract: BACKGROUND
  Accumulating evidence supports the notion that the pathogenesis of severe lupus glomerulonephritis is multifactorial and not solely an immune complex-mediated glomerular disease. Alternate mechanisms for glomerular destruction may exist.
  
  
  METHODS
  We conducted a retrospective clinicopathologic analysis of 213 patients with lupus nephritis. Twenty-six patients had severe segmental glomerulonephritis (SSGN) and 15 patients had diffuse proliferative glomerulonephritis (DPGN). Patients with pure mesangial lupus nephritis [mesangial glomerulonephritis (MesGN)] (N = 13) were used as histologic controls. The degree of immunologic activity detailed by histologic data including light, fluorescent (IF) and electron microscopy (EM) on kidney biopsies and clinical data from patients with severe lupus nephritis were analysed.
  
  
  RESULTS
  Biopsies from patients with SSGN had fewer glomeruli with wire loops (3 +/- 6% versus 35 +/- 34% P = 0.005) and hyaline thrombi (0.8 +/- 3% versus 16 +/- 22%, P = 0.02) compared to DPGN. The amount of IgG by IF was less in SSGN lesions compared to DPGN lesions, and IgG was absent in 30% of the SSGN group compared to none of the DPGN group (P = 0.04). There was no difference in mesangial deposits among the three groups (SSGN, DPGN and MesGN). The EM data supported the IF data. Anti-neutrophil cytoplasmic antibodies (ANCA) were essentially negative in all three groups and the C3 values tended to be lower in DPGN compared to SSGN (48 +/- 15 mg/dl versus 60 +/- 26 mg/dl, P = 0.09).
  
  
  CONCLUSIONS
  The findings in DPGN involve a classic immune complex-mediated glomerulonephritis as demonstrated by the abundant immune aggregates witnessed in the peripheral capillary wall. In contrast, a paucity of peripheral immune aggregates is seen in SSGN implying a different pathogenesis. Our data support a mechanism of glomerular injury in SSGN that is separate from the generally accepted unitary concept of immune complex deposition in lupus nephritis.
authors.affiliation: Department of Medicine, Division of Nephrology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Venkata Y
authors.initials: VY
authors.lastname: Behara
authors.forename: William L
authors.initials: WL
authors.lastname: Whittier
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Korbet
authors.forename: Melvin M
authors.initials: MM
authors.lastname: Schwartz
authors.forename: Mildred
authors.initials: M
authors.lastname: Martens
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism; D001706:Biopsy; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D008181:Lupus Nephritis / Q000209:etiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007074:Immunoglobulin G