Background/Purpose:  Neutrophilia and elevated neutrophil-to-lymphocyte ratio are being increasingly recognized as reliable markers of inflammation (and usually negative prognostic outcome) in scenarios as diverse as trauma, cancer, and autoimmune disease. While lymphopenia is well established as a marker of lupus activity, why and when lupus patients develop elevated neutrophil counts (neutrophilia) have not been comprehensively explored. Lupus neutrophils are known to produce interferons, release mitochondria, and expel neutrophil extracellular traps (NETs), all of which may be detrimental to the patient.

Methods:  From a U.S. lupus cohort of more than 800 patients, we randomly selected 75 patients for a pilot study. Neutrophilia was defined as absolute neutrophil count higher than the upper limit of normal for the institution’s laboratory, which was 7.2-7.5 K/µl, depending on the era. Charts were evaluated by two independent reviewers, and each episode was assigned to one of four categories: infection, corticosteroid burst, pregnancy, or unknown. All patients met American College of Rheumatology classification criteria for systemic lupus erythematosus.

Results:  In characterizing 75 lupus patients, we identified 2,892 neutrophil measurements over a 20-year period (2001-2016). The median number of neutrophil measurements per patient was 22 (range 2 to 279). Of the 75 patients, 27 patients had no documented episodes of neutrophilia (median number of tests 8, range 2 to 89). We identified 227 unique episodes of neutrophilia (separated by at least 4 weeks, and not part of a continuous event such as an extended hospitalization). Of the 227 episodes of neutrophilia, 26 fell between 7 and 8 K/µl; 72 between 8 and 9; 36 between 9 and 10; 85 between 10 and 20; and 8 between 20 and 30. Of the 227 episodes, 41 were attributed to infection (median neutrophil count 11.2 K/µl), 79 to corticosteroid burst (median neutrophil count 10.8), and 11 to pregnancy (median neutrophil count 9.5). The most common infections causing neutrophilia were pneumonia and urinary tract infections. 96 cases of neutrophilia (median neutrophil count 8.6) could not be attributed to any of the aforementioned explanations, and we considered that they might associate with heightened disease activity.

Conclusion:   Neutrophilia in lupus patients is explained by infection, corticosteroid burst, or pregnancy 58% of the time. In the remaining cases, the explanation is not readily apparent, and analysis is underway to assess the possible contribution of disease activity (preliminary analysis is pointing away from a correlation). These unexplained neutrophilia cases did seem to cluster in a relatively small number of patients, suggesting that there may be particular lupus phenotypes that correlate with neutrophil elevations; analysis is underway in the larger cohort to define those phenotypes. The next phase of this work should also seek to correlate neutrophil counts with not just traditional markers of disease activity, but also novel readouts such as circulating NETs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/neutrophilia-in-systemic-lupus-erythematosus-as-a-potential-indicator-of-disease-activity/