Flow cytometric immunophenotyping in the diagnosis and follow-up of immunodeficient children

From time to time, paediatricians are confronted with children who might suffer from a primary immunodeficiency disease. For practical purposes, these children can be divided into four main clinical categories: (1) a relatively large group of children with recurrent ear-nose and throat and lower respiratory tract infections, in some cases caused by deficiencies of antibodies or complement; (2) children with failure to thrive, intractable diarrhoea or an opportunistic infection which can be caused by a T-lymphocyte or combined immunodeficiency; (3) children with infections with pyogenic bacteria or fungi as seen in case of granulocyte/monocyte function deficiency; and (4) a small heterogeneous group of children with recurrence of particular infections. Also, acquired immunodeficiency becomes a more common problem in paediatric practice. Flow cytometric immunophenotyping of leucocytes appears to be an efficient and rapid tool in the diagnosis and follow-up of immunodeficient patients, supporting early recognition, before serious infections have compromised the child's general condition. This technique can now be performed in many hospitals. In this review, we give directions for the use of flow cytometric immunophenotyping of leucocytes in the diagnosis and follow-up of immunodeficient children according to the four main clinical categories.     

Neutrophil interactions with T cells,platelets, endothelial cells,and of course tumor cells

Neutrophils sense microbes and host inflammatory mediators, and traffic to sites of infection where they direct a broad armamentarium of antimicrobial products against pathogens. Neutrophils are also activated by damage-associated molecular patterns (DAMPs), which are products of cellular injury that stimulate the innate immune system through pathways that are similar to those activated by microbes. Neutrophils and platelets become activated by injury, and cluster and cross-signal to each other with the cumulative effect of driving antimicrobial defense and hemostasis. In addition, neutrophil extracellular traps are extracellular chromatin and granular constituents that are generated in response to microbial and damage motifs and are pro-thrombotic and injurious. Although neutrophils can worsen tissue injury, neutrophils may also have a role in facilitating wound repair following injury. A central theme of this review relates to how critical functions of neutrophils that evolved to respond to infection and damage modulate the tumor microenvironment (TME) in ways that can promote or limit tumor progression. Neutrophils are reprogrammed by the TME, and, in turn, can cross-signal to tumor cells and reshape the immune landscape of tumors. Importantly, promising new therapeutic strategies have been developed to target neutrophil recruitment and function to make cancer immunotherapy more effective.     

Ocrelizumab Concentration Is a Good Predictor of SARS-CoV-2 Vaccination Response in Patients with Multiple Sclerosis

Ocrelizumab, an anti-CD20 monoclonal antibody, counteracts induction of humoral immune responses after severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccinations in patients with multiple sclerosis (MS). We aimed to assess if serum ocrelizumab concentration measured at the time of vaccination could predict the humoral response after SARS-CoV-2 vaccination. In 52 patients with MS, we found ocrelizumab concentration at the time of vaccination to be a good predictor for SARS-CoV-2 IgG anti-RBD titers after vaccination (comparable to B-cell count). As the course of ocrelizumab concentration may be predicted using pharmacokinetic models, this may be a superior biomarker to guide optimal timing for vaccinations in B-cell depleted patients with MS. ANN NEUROL 2023;93:103–108