Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis

Abstract

The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome.A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome.The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%).In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options.

FIGURE 1

Kidney biopsy from a patient with SLE/AAV overlap syndrome. Patient 7 presented with rapidly progressive glomerulonephritis (GN) following anti-TNF therapy for polyarthritis, with positive ANCA and anti-MPO antibodies. Renal pathology shows crescentic glomerulonephritis compatible with pauci-immune GN, but with unexpected mesangial enlargement and immune-complex deposits in immunofluorescence analysis, which led to a search for the SLE criteria and a diagnosis of SLE/AAV overlap syndrome. (A) Optical analysis: the glomerulus on the left shows fibrinoid necrosis and a cellular crescent, whereas the glomerulus on the right shows discrete mesangial enlargement, without proliferation (Jones methenamine silver, ×100 magnification). (B) Immunofluorescence analysis: the presence of diffuse mesangial immune-complex deposits of IgG (+), IgM (±), C3 (+), and C1q (±) (IgG + shown here, ×200 magnification). AAV = ANCA-associated vasculitis, GN =  glomerulonephritis, MPO = myeloperoxidase, SLE = systemic lupus erythematosus.