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Utility of neutrophil CD64 and serum TREM-1 in distinguishing bacterial infection from disease flare in SLE and ANCA-associated vasculitis

Abstract

Bacterial and opportunistic infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis owing to treatment with immunosuppressants. Commonly used laboratory tests are unreliable in differentiating infection from active disease patients. Fc receptor (FcγR1 or CD64) expression on neutrophils and soluble TREM-1 (triggering receptor expressed on monocytes) are potential biomarkers of bacterial infections. Our aim was to measure the clinical usefulness of quantitative CD64 measurement on neutrophils and soluble TREM-1 measurements in differentiating bacterial infection from active disease in patients with SLE and ANCA vasculitis. Patients with bacterial infection (n = 25), active disease (n = 51), and healthy controls (n = 20) were included. Neutrophil CD64 expression using flow cytometry and sTREM-1 and procalcitonin levels by ELISA were studied. The percentage of neutrophils with CD64 expression and their mean fluorescence intensity in patients with infection (68.8 (56.9–86.5)%, 1037 (229–1828)) were significantly (p < 0.05) higher as compared to those without infection (7.7 (2.6–13.1)%, 456 (20–968)) and controls (7.05 (1.4–9.5)%, 99.5 (54.7–140.7)). The sensitivity and specificity of CD64 expression on neutrophils to diagnose bacterial infection (using a cutoff value of 30%) was 85% and 84%, respectively, whereas the sensitivity and specificity of procalcitonin was 75% and 85%, respectively. There was no significant difference in soluble TREM-1 levels between the two groups. Quantitative measurement of CD64 on neutrophils can distinguish between systemic infection and the flare of autoimmune diseases.

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Abbreviations

AAV:

ANCA-associated vascuilitis

ANCA:

Anti-neutrophil-associated cytoplasmic antibody

ELISA:

Enzyme-linked immunosorbent assay

ESR:

Erythrocyte sedimentation rate

MAS:

Macrophage activation syndrome

MFI:

Mean fluorescence intensity

PBS:

Phosphate-buffered saline

PMN:

Polymorphonuclear leukocytes

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

TREM:

Triggering receptor expressed on monocytes

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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Correspondence to Vikas Agarwal.

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The pertinent ethical committee has given its approval and/or the reported investigations have been performed in accordance with the principles of the Declaration of Helsinki.

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Ajmani, S., Singh, H., Chaturvedi, S. et al. Utility of neutrophil CD64 and serum TREM-1 in distinguishing bacterial infection from disease flare in SLE and ANCA-associated vasculitis. Clin Rheumatol 38, 997–1005 (2019). https://doi.org/10.1007/s10067-018-4334-5

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Keywords

  • AAV
  • ANCA-associated vasculitis
  • Biomarker
  • CD64
  • Sepsis
  • SLE