Could a simple biomarker as neutrophil-to-lymphocyte ratio reflect complex processes orchestrated by neutrophils?

The complex pathological mechanisms of autoimmune diseases have now been discovered and described, including interactions between innate and adaptive immunity, the principal cells of which are neutrophils and lymphocytes. Neutrophil-to–lymphocyte ratio (NLR) was proposed as a biomarker for inflammation that reflects the balance between these aspects of the immune system. NLR is widely studied as a prognostic or screening parameter in quantity diseases with important inflammatory components such as malignancies, trauma, sepsis, critical care pathology, etc. Although there are still no consensually accepted normal values for this parameter, there is a proposal to consider an interval of 1–2 as a normal value, an interval of 2–3 as a grey area indicating subclinical inflammation and values above 3 as inflammation.On the other hand, several studies have been published indicating that a particular morphological type of neutrophils, low-density neutrophils (LDNs), play a pathological role in autoimmune diseases. Probably, the LDNs detected in patients with different autoimmune diseases, mostly than normal density neutrophils, are involved in the suppression of lymphocytes through different pathways: inducing of lymphopenia through neutrophil depending overproduction of type I interferon (IFN)-α/β and direct suppression by a hydrogen-peroxide-dependent mechanism. Their functional features involvement in IFN production is of particular interest. IFN is one of the critical cytokines in the pathogenesis of many autoimmune diseases, primarily systemic lupus erythematosus (SLE). An interesting and important feature of IFN involvement in the pathogenesis of SLE is not only to be directly related to lymphopenia but also its role in the inhibition of the production of C-reactive protein (CRP) by hepatocytes. The CRP is the primary acute phase reactant, which in SLE often does not correlate with the extent of inflammation. NLR in such a case can be an important biomarker of inflammation. The study of NLR as a biomarker of inflammation also deserves attention in other diseases with established interferon pathways, as well as in hepatopathies, when CRP does not reflect the proper inflammation activity. Also, it may be interesting to study its role as a predictor of relapses in autoimmune diseases

Neutrophil Extracellular Traps, Antiphospholipid Antibodies and Treatment

Neutrophil extracellular traps (NETs) are a network of extracellular fibers, compounds of chromatin, neutrophil DNA and histones, which are covered with antimicrobial enzymes with granular components. Autophagy and the production of reactive oxygen species (ROS) by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are essential in the formation of NETs. There is increasing evidence that suggests that autoantibodies against beta-2-glycoprotein-1 (B2GP1) induce NETs and enhance thrombosis. Past research on new mechanisms of thrombosis formation in antiphospholipid syndrome (APS) has elucidated the pharmacokinetics of the most common medication in the treatment of the disease

Obstetric antiphospholipid syndrome

Antiphospholipid syndrome (APS) in pregnancy has a serious impact on maternal and fetal morbidity. It causes recurrent pregnancy miscarriage and it is associated with other adverse obstetric findings like preterm delivery, intrauterine growth restriction, preeclampsia, HELLP syndrome and others. The 2006 revised criteria, which is still valid, is used for APS classification. Epidemiology of obstetric APS varies from one population group to another largely due to different inclusion criteria and lack of standardization of antibody detection methods. Treatment is still controversial. This topic should include a multidisciplinary team and should be individualized. Success here is based on strict control and monitoring throughout pregnancy and even in the preconception and postpartum periods. Further research in this field and unification of criteria are required to yield better therapeutic strategies in the future. © 2011 Elsevier B.V

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women

International audienceTo evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further