Reumatología Clínica

Reumatología Clínica

Volume 15, Issue 6, November–December 2019, Pages 363-367
Reumatología Clínica

Brief report
Clinical Significance of Neutrophil/lymphocyte Ratio in Patients With Granulomatosis With PolyangiitisSignificación clínica del ratio neutrófilos/linfocitos en pacientes con granulomatosis con poliangeítis

https://doi.org/10.1016/j.reuma.2017.11.003Get rights and content

Abstract

Objective

To determine to neutrophil-to-lymphocyte ratio (NLR) in granulomatosis with polyangiitis (GPA) patients and to study its relation to disease manifestations and activity.

Methods

The study included 44 GPA patients and 44 matched age and sex controls. Full history taking, thorough clinical examination with more attention to ocular examination, laboratory and radiological investigations were considered. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS).

Results

The patients (21 males and 23 females) had a mean age of 45.66 ± 7.24 years, disease duration 6.8 ± 3.6 years and BVAS 50.1 ± 14.3. All patients had a positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) while only 5 had a positive p-ANCA. The NLR was significantly increased in the GPA patients (5.1 ± 2.4) compared to the control (1.5 ± 0.8) (P < .0001). Ten patients with uveitis had a significantly higher NLR (6.5 ± 1.9) compared to those without (4.7 ± 2.4) (0.03) while those with proptosis (n = 10), cutaneous manifestations (n = 17) or ischemic heart disease (n = 9) had a significantly lower NLR than those without (P = .0001, P = .017 and P = .046 respectively). The NLR did not significantly correlate with any of the patients’ characteristics. The NLR inversely yet insignificantly correlated with the disease activity (r = -0.02, P = .93).

Conclusion

The NLR may have a significant role in the pathogenesis of GPA, the development of uveitis or proptosis, cutaneous manifestations and ischemic heart disease. NLR may serve as a future potential companion to c-ANCA positivity in diagnosing and evaluating GPA and may play a role in the tissue-specific and clinical characteristics.

Resumen

Objetivo

Determinar el ratio neutrófilos/linfocitos (RNL) en pacientes con granulomatosis con poliangeítis (GP), y estudiar su relación con las manifestaciones y actividad de la enfermedad.

Métodos

El estudio incluyó a 44 pacientes con GP, y 44 controles pareados por edad y sexo. Se consideraron la historia clínica completa, la exploración minuciosa con especial atención al examen ocular, así como las pruebas de laboratorio y radiológicas. La actividad de la enfermedad se evaluó utilizando la clasificación Birmingham Vasculitis Activity Score (BVAS).

Resultados

Los pacientes (21 varones y 23 mujeres) tenían una edad media de 45,66 ± 7,24 años, duración de la enfermedad de 6,8 ± 3,6 años, y BVAS 50,1 ± 14,3. Todos los pacientes tenían anticuerpos anticitoplasma de anti-neutrófilos positivos (c-ANCA), y únicamente 5 de ellos tenían p-ANCA positivo. El RNL se vio significativamente incrementado en los pacientes de GP (5,1 ± 2,4) en comparación con el grupo control (1,5 ± 0,8) (p < 0,0001). En 10 pacientes con uveítis se observó un RNL significativamente superior (6,5 ± 1,9) en comparación con aquellos sin uveítis (4,7 ± 2,4) (0,03), mientras que en aquellos con proptosis (n = 10), manifestaciones cutáneas (n = 17) o cardiopatía isquémica (n = 9) se observó un RNL significativamente inferior al de aquellos sin dichas manifestaciones (p = 0,0001; p = 0,017 y p = 0,046, respectivamente). El RNL no guardó una correlación significativa con ninguna de las características de los pacientes. Sin embargo, el RNL guardó una correlación no significativa con la actividad de la enfermedad (r = -0,02; p = 0,93).

Conclusión

El RNL puede desempeñar un papel significativo en la patogenia de la GP, el desarrollo de uveítis o proptosis, manifestaciones cutáneas y cardiopatía isquémica. El RNL puede servir como futuro complemento potencial de la positividad de c-ANCA a la hora de diagnosticar y evaluar la GP, y jugar un papel con relación a sus características tisulares específicas y clínicas.

Introduction

Granulomatosis with polyangiitis (GPA) is an infrequent multisystemic necrotizing vasculitis, typically involving the respiratory systems and kidneys and usually runs a relapsing course.1 GPA is an antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Necrotizing granulomatous inflammation mainly involving the small-medium vessels leads to major complications up to mortality with increased resistance to medications.2 In this disease, proteinase-3 (PR3), produced by neutrophils, is targeted by ANCA.3

Neutrophils are important in the defense against pathogens, in modulating inflammation and in fine-tuning immune responses.4 They are actively involved in systemic and local inflammatory responses by releasing pro-inflammatory elements5 thus playing a role in many rheumatic diseases, yet the underlying molecular mechanisms are not fully revealed.4 Neutrophils may be identified in the lesions of virtually all kinds of vasculitis with variable mechanisms of accumulation. In AAV diseases, partial neutrophil degranulation results in exposure of ANCA antigens (myeloperoxidase ‘MPO’ and PR3).6 Neutrophils play an immunostimmulant role in the pathogenesis of GPA.7 A wide range of antigens are recognized by lymphocytes and the immune system contains subpopulations specialized in recognizing conserved structures. Given the numerous steps in the development of lymphocytes, it is expected that many causes may lead to their immunodeficiency.8 Increased frequency of Th-cells in ANCA-positive GPA patients throw light on a possible role of these cells in the immunopathogenesis of the disease.9 Of the ANCA-associated vasculitides, GPA best demonstrates the theory that autoimmunity can develop against one specific neutrophil protein, namely, PR3. The unique features of PR3 are primary contributors to the systemic inflammation and to the immune dysregulation involved in GPA.4

The neutrophil-to-lymphocyte ratio (NLR) is a useful marker that predicts not only disease progression, but also mortality in different inflammatory diseases1 making it noticeable as a new biomarker of inflammation.5

The Birmingham Vasculitis Activity Score (BVAS) is a regular activity score used in GPA. Even though anti-PR3 antibodies are specific for GPA, the role of its level or of any other laboratory test as an activity marker has not been established.10, 11, 12

The aim of the present work was to determine to NLR in GPA patients and to study its relation to disease manifestations and activity.

Section snippets

Patients and Methods

The study included 44 GPA patients recruited from Ain Shams and Alexandria University hospitals diagnosed according to the 1990 American College of Rheumatology criteria for GPA.13 Forty-four matched age and sex controls were also included. The study is in accordance to the 1995 Helsinki declaration and approved by the ethical committee of Ain Shams and Alexandria Universities’ Hospitals. Informed consent was obtained from all patients. Patients with diabetes mellitus, chronic renal failure,

Results

The study included 44 GPA patients (21 males and 23 females) with a mean age of 45.66 ± 7.24 years and 44 matched control for age (43.07 ± 10.15 years; P = .17) and gender (P = .83). The disease duration of the patients was 6.8 ± 3.6 years and their mean body mass index was 25.4 ± 2.4 and 24 (54.5%) were hypertensive. None of the patients had any associated inflammatory conditions. The clinical and laboratory findings as well as the BVAS of the GPA patients are presented in Table 1. Ten patients had

Discussion

Granulomatosis with polyangiitis is a vasculitis with potential morbidity and mortality.16 In GPA, neutrophils play a pivotal role in its pathology.17 c-ANCAs are present in 90% of GPA patients. As the humoral immunity is predominantly directed against neutrophilic antigens, it is apparent that neutrophils play a critical role in GPA both as target and effector cells.18 The pathophysiological importance of PR3-ANCA is not yet understood and the pathogenic pathways leading to granuloma formation

Conflict of Interest

None declared.

References (35)

  • K.R. Martin et al.

    Proteinase 3: the odd one out that became an autoantigen

    J Leukoc Biol

    (2017)
  • B. Shah et al.

    Neutrophils

  • C. Lange et al.

    Immune stimulatory effects of neutrophil extracellular traps in granulomatosis with polyangiitis

    Clin Exp Rheumatol

    (2017)
  • W.H. Abdulahad et al.

    Increased frequency of circulating IL-21 producing Th-cells in patients with granulomatosis with polyangiitis (GPA)

    Arthritis Res Ther

    (2013)
  • C.G. Kallenberg

    Pathogenesis of ANCA-associated vasculitides

    Ann Rheum Dis

    (2011)
  • L. Lally et al.

    Biomarkers in ANCA-associated vasculitis

    Curr Rheumatol Rep

    (2013)
  • W. Merkt et al.

    Peripheral blood natural killer cell percentages in granulomatosis with polyangiitis correlate with disease inactivity and stage

    Arthritis Res Ther

    (2015)
  • Cited by (13)

    • Old known and possible new biomarkers of ANCA-associated vasculitis

      2022, Journal of Autoimmunity
      Citation Excerpt :

      For clinical practice, measurement of granularity index may be of most interest in identifying patients who respond best to different therapeutic strategies in AAV, but still requires a prospective study for validation. Although several retrospective studies showed that increased NLR is associated with increased disease severity [264–268], increased risk of infection, and increased risk of recurrence of AAV, due to the fact that also infections, tumor diseases, trauma, psychiatric diseases, cardiac and pulmonary diseases, rheumatic diseases also lead to increased NLRs [269], the determination of NLRs is not practical in clinical practice. The rather simple determination of the platelet count and a possible distinction between active and remission vasculitis as well as between active vasculitis disease and systemic infection has also been part of clinical research in recent years.

    • Hematologic parameters and disease activity in patients with primary Sjögren's syndrome

      2022, Egyptian Rheumatologist
      Citation Excerpt :

      In Behcet's disease (BD), NLRandRDW levels were high and clearly associated with ESR and CRP [33]. A significantly higher NLR level was also reported in patients with granulomatosis with polyangiitis (GPA) [34]. In SLE, higher NLR levels were related to the severity of disease activity, and the recurrence and progression of lupus nephritis [35].

    • The neutrophil-to-lymphocyte ratio as a marker of vasculitis activity, severe infection and mortality in anca-associated vasculitis: A retrospective study

      2021, Nefrologia
      Citation Excerpt :

      Validation of this practical, inexpensive and easily calculated biomarker has been explored in AAV patients, with early studies suggesting a positive relation between the NLR and BVAS, acute phase reactants and worse renal outcomes.31 Other studies, however, have shown conflicting results between the ratio and disease activity as well as extrarenal manifestations.32 Recently, Ahn et al. retrospectively analyzed 160 AAV patients and reported that an elevated NLR was correlated with vasculitis activity estimated by BVAS at diagnosis and predicted relapse during follow-up (Patients having NLR ≥5.9 exhibited severe AAV more frequently than those having NLR < 5.9 at diagnosis (relative 2.189, p = 0.023).).33

    View all citing articles on Scopus
    View full text