The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.
Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14++CD16+ monocytes, CD56+ CD16dim natural killer cells, marginal zone-like IgD+CD27+ B cells, and on CD4+ and CD8+ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.
ObjectiveTreatment-refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition without evidence-based treatment options. One emerging treatment option for several antibody-mediated autoimmune diseases is the anti-CD38 antibody daratumumab, which depletes autoantibody-secreting plasma cells.MethodsWe treated two patients with severe life-threatening AAV with renal and pulmonary manifestation despite induction therapy with rituximab and cyclophosphamide with four to eight doses of 1800 mg daratumumab. We followed clinical and immunological responses.ResultsThe first patient with myeloperoxidase-ANCA-positive microscopic polyangiitis had resolution of pneumonitis and pleuritis and stabilisation of kidney function after daratumumab. The second patient with proteinase 3-ANCA-positive granulomatosis with polyangiitis, diffuse alveolar haemorrhage necessitating extracorporeal membrane oxygenation (ECMO) and acute kidney failure, requiring kidney replacement therapy, was weaned off ECMO, mechanical ventilation and dialysis and discharged home after daratumumab. Clinical improvement was paralleled by a strong reduction in serum ANCA levels as well as total IgG, indicating depletion of plasma cells. Apart from the depletion of CD38+natural killer cells, blood leucocyte levels were not notably influenced by daratumumab. Only mild adverse events, such as hypogammaglobulinaemia and an upper respiratory tract infection occurred.ConclusionDaratumumab was safe and effective in inducing remission in two patients with severe treatment-refractory AAV, warranting prospective clinical trials to establish safety and efficacy.
Objectives To evaluate and compare the diagnostic accuracy of SIGLEC1, a surrogate marker of type I IFN, with established biomarkers in an inception cohort of systemic lupus erythematosus (SLE). Methods SIGLEC1 was analyzed by flow cytometry in 232 patients referred to our institution with suspected SLE between October 2015 and September 2020. Results SLE was confirmed in 76 of 232 patients (32.8%) according to the 2019 EULAR/ACR classification criteria and their SIGLEC1 values were significantly higher compared with patients without SLE (p< 0.0001). A sensitivity of 98.7%, a specificity of 82.1%, a negative predictive value (NPV) of 99.2% and a positive predictive value (PPV) of 72.8% were calculated for SIGLEC1. Adjusted to the highest reported prevalence of SLE, the NPV and PPV were > 99.9% and 0.1%, respectively. Using ROC analysis and Delong testing, the area under the curve (AUC) for SIGLEC1 (AUC = 0.95) was significantly higher than for ANA (AUC = 0.88, p= 0.031), C3 (AUC = 0.83, p= 0.001) and C4 (AUC = 0.83, p= 0.002) but not for anti-dsDNA antibodies (AUC = 0.90, p= 0.163). Conclusion IFN-I pathway activation is detectable in almost all newly diagnosed SLE patients. Thus, a negative test result for SIGLEC1 is powerful to exclude SLE in suspected cases.
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