Background/Purpose: Neutrophils and neutrophil death (“netosis”) are now understood to play a role in the pathogenesis of SLE. A neutrophil gene signature exists in SLE, although its association with the clinical phenotype is unknown.

Methods: A total of 292 SLE patients were included in the analysis. Among these patients, 91.1% were female; 58.9% were Caucasian, 33.9% were African-American, and 7.2% were other ethnicities. Mean age (standard deviation) at baseline was 46.0 (±11.9) years. Neutrophil gene expression was high (>6) in 31.9% (N=93), medium (5-6) in 31.5% (N=92), and low (<5) in 36.6% (N=107) of patients.

Results:

The neutrophil gene signature was more common in Caucasians (p=0.045). The neutrophil gene signature is strongly associated with same day disease activity, serologies (anti-dsDNA and low complements), and need for prednisone. It is also strongly associated with poor outcomes (myocardial infarction, deep venous thrombosis, diabetes, malignancy).

Table 1. Association between Same-day Visit Disease Activity and Neutrophil Gene Signature

Variable	Low Neutrophil (<5) (%, N=107)	Med Neutrophil (5-6) (%, N=92)	High Neutrophil (>6) (%, N=93)	Adjusted P-value for Ethnicity
Ethnicity   African-American                  Caucasian                  Other	36.5 57.9 5.6	42.4 52.2 5.4	22.6 66.7 10.8	0.045*
Physician’s global assessment >1	11.2	16.3	30.1	0.003
SELENA SLEDAI ≥2	47.7	60.9	65.6	0.012
Age at visit (years)      ≤30                                     >30	13.1 86.9	9.8 90.2	12.9 87.1	0.75
Use of Prednisone	25.2	32.6	49.5	0.0007
Use of Plaquenil	77.6	88.0	71.0	0.016
Use of Aspirin	30.8	41.3	51.6	0.011
Anti-dsDNA ≥10	10.3	26.1	31.2	0.0005
Lupus Anticoagulant	10.3	12.0	23.7	0.023
C3 <79 mg/dl	8.4	8.7	20.4	0.031
C4 <12 mg/dl	5.6	9.8	18.3	0.034
ESR >20	40.2	53.4	61.5	0.0018

* Unadjusted p-value.

Table 2. Association between SLICC/ACR Damage Index and Neutrophil Gene Expression in SLE

 

Variable	Low Neutrophil (<5) (%, N=107)	Med Neutrophil (5-6) (%, N=92)	High Neutrophil (>6) (%, N=93)	Adjusted P-value for Ethnicity
Myocardial Infarction	0.0	6.5	5.4	0.0056
Deep Venous Thrombosis	1.9	0.0	6.5	0.016
Diabetes	4.7	6.5	14.1	0.024
Malignancy	2.8	12.1	15.2	0.0043

 Conclusion: This is the first gene signature to be associated with myocardial infarction, deep venous thrombosis and malignancy. Targeting the neutrophil gene signature appears to be promising for disease activity. Given that atherosclerosis disease is the major cause of death in late SLE, this gene signature may be the “missing link” in understanding how SLE accelerates atherosclerosis. A limitation of the technique is that the neutrophil gene signature will go up when there is lymphopenia.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-neutrophil-gene-signature-and-disease-characteristics-in-systemic-lupus-erythematosus-patients/