Assessing neutrophil subsets in autoimmune disease: Moving away from relying on density?

Neutrophils are the most abundant immune cell in circulation. However, due to a number of technical challenges for researchers, including neutrophil's short lifespan and difficulties with preservation, they often discarded during blood processing thus ignored cohort studies. As such, contribution neutrophils disease their involvement mechanisms is less explored compared other types. Systemic lupus erythematosus (SLE) heterogenous, multi-organ, autoimmune where autoantibodies against nuclear antigens common. With discovery neutrophil extracellular traps (NETs), which chromatin complexes released by that harbour many autoantigens observed SLE, SLE pathology has gained much attention over last decade. In addition, interferon (IFN)-responsive low-density (LDN) significantly more prominent SLE.1 Thus, now considered central player pathology. LDN isolated peripheral mononuclear layer density gradient-based separation. rare healthy individuals but can be SLE2 autoimmune, cancerous or infectious conditions, such as multiple sclerosis3 tuberculosis. display activation IFN genes, upregulation acute phase proteins produce reactive oxygen species NETs normal neutrophils, suggests may contribute A recent study also suggested an altered morphology, leading being easily trapped narrow vessels possibly contributing cardiovascular manifestations common SLE.4 heterogenous population likely induced through several pathways exposures, impact functional characteristics. example, from cancer patients appear immunosuppressive properties suppress T activation.5 however, do not have suppressive characteristics, rather activation.6 The ratio mature immature LDN, maturity defined expression CD10, contributes pro- anti-inflammatory LDN. This differs pathological relate disparity described LDN.7 CD10+ main producers NETs, efficient phagocytosis, myeloperoxidase CD10− LDN.8 Moreover, individuals, higher content mitochondrial DNA. These oxidised inflammatory/immunogenic lower proportion DNA.9 represent target better methods identifying them patient samples would important tools could significant implications management this disease. So far, no definitive marker whole been identified. Currently, CD10 used maturation majority CD10−/immature when individuals. CD10+, evident above, essential characteristics population; therefore, further markers required identify blood. Recent work Martin et al.10 whole-cell proteomic analysis CD98 potential new surface involved adhesion amino acid transportation. It expressed across types, monocytes, typically on normal-density neutrophils. Following granulocyte-colony stimulating factor administration upregulates trafficking bone marrow blood, was vast circulating patients, approximately two-thirds were CD98+, controls. aligns heterogeneity SLE-LDN population. Nevertheless, found correlated activity. role metabolic flexibility it facilitated uptake acids mitochondrial-dependent adenosine triphosphate production. inhibiting apoptotic responses alongside intact necroptotic responses. provides molecular mechanism adapt inflammatory environment. evaluated therapeutic target, antagonist reduce survival tissue damage inflammation. summary, pathogenesis continues become clearer, shows some promise either useful biomarker assays novel SLE. advancing knowledge diseases increased observed. supported MSWA. authors declare conflict interest.