Antineutrophil autoantibodies and their target antigens in systemic lupus erythematosus

Abstract

Various autoantibodies have been identified in sera from patients with systemic lupus erythematosus (SLE) and autoantibodies against neutrophil have been reported. It was suggested that antineutrophil autoantibodies might be involved in the pathogenesis of neutrocytopenia; however, the role of autoantibodies against neutrophil precursors and their specific target autoantigen(s) remained further characterized. The objective was to investigate the target antigens and clinical associations of autoantibodies against neutrophils and neutrophil precursors in patients with SLE. Sera were collected from 92 patients with SLE and renal biopsy proven lupus nephritis. Cell lysates of peripheral neutrophils (as mature neutrophils) from a normal blood donor and white blood cells from a patient with blast crisis of chronic granulocytic leukemia (CGL) (as neutrophil precursors) were used as antigens in Western blot analysis to detect autoantibodies in sera from patients with SLE. The clinical significance of antineutrophil autoantibodies that recognized different antigens were further analysed. Using normal peripheral neutrophils as antigens, two bands could be blotted: 64 kD (33/92, 35.9%) and 50 kD (13/92, 14.1%). The prevalence of anti-64 kD autoantibody in patients with positive rheumatic factor was significantly higher than that in patients without (54.5 versus 18.8%, P < 0.05). Using CGL white cells as antigen, five bands could be blotted: 60 kD (34/92, 37.0%), 50 kD (32/92, 34.8%), 29 kD (27/92, 29.3%), 42 kD (19/92, 20.7%) and 18 kD (16/92, 17.4%). The prevalence of anti-60 kD autoantibody was significantly higher in patients with neutrocytopenia than that in patients without neutrocytopenia (100 versus 48.3%, P < 0.01). The prevalence of anti-29 kD autoantibody was significantly higher in patients with alopecia than that in patients without alopecia (45.8 versus 20.8%, P < 0.05). Furthermore, the prevalences of anti-60 kD, anti-50 kD and anti-42 kD autoantibodies were significantly higher in patients with anti-Ro autoantibody than those in patients without; the prevalences of anti-29 kD and anti-18 kD autoantibodies were significantly higher in patients with anti-Sm autoantibody than those in patients without. We conclude that there are heterogeneous autoantibodies against both neutrophils and their precursors in sera from patients with SLE. Different autoantibodies may have different clinical significance.

Systemic lupus erythematosus and antineutrophil cytoplasmic antibody–associated vasculitis: An emerging overlap syndrome with cutaneous manifestations

“… 4 Although ANCA antibodies occur in approximately 16% of patients with SLE, it is unclear whether this serologic finding is of clinical significance, as few of these patients have concomitant ANCA-associated vasculitis. 5 , 6 , 7 Furthermore, nonspecific assays for ANCAs may cross react with ANAs because of an artifact in ethanol fixation, potentially confounding any true associations. 8 …”

Antineutrophil cytoplasmic autoantibodies in patients with systemic lupus erythematosus recognize a novel 69 kDa target antigen of neutrophil granules

“…Therefore, unknown target antigens of ANCA still need to be identified. 20 In the current study, a target antigen with molecular weight of 69 kDa was found from neutrophil granules. As shown before, all of the 72 sera were tested for ANCA by antigen-specific ELISA.…”

“…However, some sera from patients with SLE had positive ANCA by indirect immunofluorescence using ethanol‐fixed neutrophils as substrate, but did not recognize either of the above specific ANCA antigens. Therefore, unknown target antigens of ANCA still need to be identified 20 …”

Association of Monocyte to High-Density Lipoprotein Cholesterol Ratio with Carotid Artery Intima-Media Thickness in Patients with Systemic Lupus Erythematosus

“…According to research reports, leukopenia has the following main reasons: autoantibodies mediate the destruction of hematopoiesis precursor cell and mature cells; TNF-mediated cell apoptosis; and drug intervention. However, granulocytes and lymphocytes were largely reduced; monocytes were not significantly affected [16][17][18]. Knowing that lower HDL-C has been considered to be a risk factor in general population.…”