Abstract

BackgroundSerum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry–based assay. The phagocytosis of necrotic cell material (PNC) assay parallels the well-known lupus erythematosus cell test. In this study, we aimed to investigate the diagnostic accuracy of the assay and the relationship with clinical manifestations and disease activity in systemic lupus erythematosus (SLE).MethodsThe diagnostic accuracy for SLE diagnosis of the PNC assay was studied by cross-sectional assessment of blood samples from 148 healthy control subjects and a multicenter rheumatic group (MRG) of 529 patients with different rheumatic symptoms. A cohort of 69 patients with an established SLE diagnosis (SLE cohort) underwent longitudinal clinical and laboratory follow-up for analysis of the temporal relationships between PNC positivity and specific clinical manifestations.ResultsIn 35 of 529 MRG patients, 13 of whom had SLE, the PNC assay result was positive. Combined positivity of the PNC assay and anti–double-stranded DNA antibodies increased specificity and positive predictive value for SLE diagnosis to 0.99 and 0.67, respectively. In the longitudinal study, 42 of 69 SLE cohort patients had positive results in the PNC assay at least once. PNC assay positivity was associated with current hematological manifestations and could predict mucocutaneous manifestations. When combined with hypocomplementemia, PNC positivity preceded increased Systemic Lupus Erythematosus Disease Activity Index 2000 score, glomerulonephritis, and alopecia.ConclusionsSerum-mediated PNC by polymorphonuclear leukocytes is commonly but not exclusively seen in patients with SLE. The PNC assay may be used in follow-up of patients with SLE and, especially in combination with other routinely assessed laboratory tests, may help to predict flares and different clinical manifestations, including glomerulonephritis. Our results encourage further development of the PNC assay as a complementary laboratory tool in management of patients with SLE.

Highlights

  • Serum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry–based assay

  • To assess its diagnostic accuracy for systemic lupus erythematosus (SLE) diagnosis, the phagocytosis of necrotic cell material (PNC) assay was performed in the 529 multicenter rheumatic group (MRG) patients

  • By comparing patients with SLE with patients affected by other disorders, we could demonstrate that SLE is by far the most common diagnosis related to a positive outcome of PNC assay, especially in anti-double-stranded DNA (dsDNA) antibody–positive patients (Table 1)

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Summary

Introduction

Serum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry–based assay. The phagocytosis of necrotic cell material (PNC) assay parallels the well-known lupus erythematosus cell test. We aimed to investigate the diagnostic accuracy of the assay and the relationship with clinical manifestations and disease activity in systemic lupus erythematosus (SLE). Many clinical manifestations of SLE are caused by immune complex deposition in target organ and subsequent inflammation caused by complement activation and infiltration of immune cells. The first laboratory test proposed as a diagnostic tool for SLE was the lupus erythematosus (LE) cell, described in 1948 as a specific finding in bone marrow leukocytes in patients affected by SLE [19]. The assessment of LE cells by light microscopy was abandoned as a routine test in favor of other diagnostic tools, including anti-dsDNA antibody analysis

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