Brief reportClinical Significance of Neutrophil/lymphocyte Ratio in Patients With Granulomatosis With PolyangiitisSignificación clínica del ratio neutrófilos/linfocitos en pacientes con granulomatosis con poliangeítis
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.
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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.
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Cited by (13)
Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain
2024, Hipertension y Riesgo VascularOld known and possible new biomarkers of ANCA-associated vasculitis
2022, Journal of AutoimmunityCitation 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 RheumatologistCitation 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, NefrologiaCitation 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