Anna Nilsson

Karolinska Institutet | KI · Department of Women's and Children's Health

During childhood, the composition and function of the T cell compartment undergoes significant changes. In healthy individuals, primary infection with herpesviruses is followed by latency, and occasional subclinical reactivation ensures transmission and contributes to an emerging pool of memory T cells. In immunocompromised individuals, herpesvirus...

Background: Children develop symptomatic coronavirus disease 2019 (COVID-19) more rarely than adults upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pediatric oncology and hematology patients may be at increased risk of severe COVID-19 due to their underlying disease or treatment. We investigated COVID-19 and sero...

Background: Sweden adopted a different strategy than many other countries to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and kept most schools open. Initial reports from China suggested that coronavirus disease 2019 (COVID-19) was milder in children compared to adults, but there was a lack of data from immunoco...

Purpose: The blood sampling procedure is complex and prone to failure, as reflected by preanalytical errors in pediatric hospital care. The primary aim was to evaluate if the risk of preanalytical errors was higher with capillary blood sampling than with venous blood sampling, and secondary, explore specific factors associated with preanalytical e...

Objectives: Despite progress in the treatment of childhood acute lymphoblastic leukemia, severe complications are common, and the need of supportive care is high. We explored the cumulative prevalence, clinical risk factors, and outcomes of children with acute lymphoblastic leukemia, on first-line leukemia treatment in the ICUs in Sweden. Design:...

Various subsets of bone marrow mesenchymal stromal cells (BM MSCs), including fibroblasts, endothelial, fat and reticular cells, are implicated in the regulation of the hematopoietic microenvironment and the survival of long-lived antibody-secreting cells (ASCs). Nowadays it is widely acknowledged that vaccine-induced protective antibody levels are...

The immune system plays a major role in recognizing and eliminating malignant cells, and this has been exploited in the development of immunotherapies aimed at either activating or reactivating the anti-tumor activity of a patient's immune system. A wide range of therapeutic approaches involving T lymphocytes, such as programmed cell death protein...

Sequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for TLR4, MBL, and IL-1Ra were investigated in relation to clinical utility of identifying severe episodes of febrile neutropenia (FN) in a cohort of children undergoing trea...

Background: The etiology of bloodstream infections (BSIs) changes over time due to updated immunization programs, new antibiotic-use strategies, changes in patient mix and travel. Continuous surveillance can guide empiric therapy and identify targets for prevention. Method: We conducted a descriptive retrospective analysis among children <18 yea...

Infection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy children. Here, we examined whether gene-expression pro...

Objectives Loss of vaccine‐induced antibodies (Abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (ALL) is common and often necessitates re‐immunisation after cessation of treatment. Even so, some ALL survivors fail to mount or to maintain protective Abs. Germinal centres (GCs) are clusters of proliferating B cells in follicle...

Background: Extracorporeal membrane oxygenation (ECMO) is used in severe respiratory and/or circulatory failure when conventional critical care fails. Studies on patients with hematological malignancies on ECMO have shown contradictory results; immunosuppression and coagulopathy are relative contraindications to ECMO. Observations: This nationwi...

Objective The aims of this study are to validate infant vaccination data in the Swedish Vaccination Register (SVR) to the Swedish administrative coverage reports, and to assess differences in register-based vaccination coverage estimates between providers using different data reporting methods. Methods The study population included all infants bor...

Background: Several studies have shown an increasing trend in pediatric Clostridium difficile infection (CDI). However, the Public Health Agency in Sweden reports a decreasing incidence of CDI in the Swedish population since 2007. The main aim of this study is to analyze the epidemiology of CDI in children. Methods: Retrospective chart-review of...

Objective: To evaluate the roles of thiopurine methyltransferase (TPMT), inosine triphosphatase (ITPA), and Nudix hydrolase 15 (NUDT15) in 6-mercaptopurine (6-MP) sensitivity during treatment of pediatric patients with acute lymphoblastic leukemia (ALL). Study design: The study included 102 pediatric patients with ALL subject to the Nordic socie...

Aim: To identify the incidence, etiology and prognosis of acute peripheral facial nerve palsy in children in the Borrelia high-endemic region of Stockholm. Methods: The present study identified children from 0-18 years of age who visited a pediatric emergency department for acute peripheral facial nerve palsy during a one-year period from 2014-2...

Background: Antimicrobial resistance is increasing, and data on antimicrobial use in Swedish children are limited. We evaluated trends in antimicrobial use and attempted to identify targets for improving the quality of antimicrobial prescribing in a tertiary care center. Methods: One-day hospital-wide point prevalence surveys were conducted 8 ti...

Biological therapy options for the treatment of rheumatic disease target molecules that can affect the cross-talk between innate and adaptive immune responses upon vaccination. Influenza vaccination in children with rheumatic disease has been recommended, but there are only sparse data on the quality of vaccine responses from pediatric patients tre...

Aim To determine the urinary tetranor‐prostaglandin E2 metabolite in healthy infants and in hospitalized infants with upper and lower respiratory tract as well as gastrointestinal infections. Methods A prospective cross‐sectional study to determine baseline concentrations of urinary tetranor‐prostaglandin E2 metabolite was conducted in 81 healthy...

Background: Successful vaccinations rely on antibody responses. Chemokine receptors play an important role in B cell homing to differentiation niches. We assessed CXCR4, CXCR5 and CCR6 expression on B cells during HIV-1 infection and relate it to antibody responses against a HBV vaccine. Methods: Blood was obtained from 54 healthy controls and 3...

Vaccine Registers are considered important tools in both surveillance of vaccine coverage, effectiveness and safety and for research purposes. The Swedish Vaccine Register was founded in 2013 and reporting is compulsory for the care-givers by law. This is the first study using data from the Swedish Vaccine Register, with the aim of evaluating the c...

Aim: Blood analyses containing pre-analytical errors (PAEs) are hazardous for patients. This study investigated the frequency of PAEs in blood analysis and the corresponding quality indicators of the sampling process in Swedish paediatric tertiary care. Methods: Data was retrieved from the laboratory at Astrid Lindgren Children's Hospital betwee...

Aim This study examined the clinical characteristics of central line associated blood stream infections occurring within 30 days after insertion versus later infections in paediatric cancer patients, and the subsequent risk for premature catheter removal. Methods This was a retrospective study of children aged 0‐18 years who were diagnosed with ca...

During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size o...

Background Epstein–Barr virus (EBV) and cytomegalovirus (CMV) are ubiquitous and persistent herpesviruses commonly acquired during childhood. Both viruses have a significant impact on the immune system, especially through mediating the establishment of cellular immunity, which keeps these viruses under control for life. Far less is known about how...

HBV vaccine has 95% efficacy in children to prevent HBV infection and related cancer. We conducted a prospective study in HIV-1 infected children receiving ART (n = 49) and controls (n = 63) to assess humoral and cellular responses to HBV vaccine provided with three doses under an accelerated schedule of 4 weeks apart. At 1 month post-vaccination a...

Acute lymphoblastic leukaemia (ALL) is the most common type of cancer in children, accounting for approximately 25% of childhood cancer cases. As a result of effective treatments over the past decades, paediatric ALL mortality has been greatly reduced. Chemotherapy, however, has a range of harmful side effects including the loss of protective antib...

Aim: This Swedish study compared the discharge diagnosis codes used for children up to the age of five hospitalised for acute lower respiratory tract infections before and after the introduction of the pneumococcal conjugate vaccine in 2007. Methods: The International Classification of Diseases - 10(th) revision codes were used. We compared the...

Background: Asparaginase (ASP) is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). It is also known for its ability to cause side effects, such as allergy and pancreatitis, as well as lipid and coagulation disturbances. The most important laboratory abnormalities are hypertriglyceridemia (HTG) and low antithrombin (AT). HTG is...

Conclusions: We show that all children have benefitted from the reduction of CAP hospitalization after introduction of PCV. Our finding emphasizes the importance of children with chronic diseases receiving adequate vaccinations that may protect from lower respiratory diseases. What is known? • Community-acquired pneumonia is a leading infectious c...

The national Swedish immunisation programme includes vaccine against diphtheria, tetanus, polio, pertussis, Haemophilus influenzae type B, Pneumococcus as well as measles, mumps and rubella. Data were collected on hospital admissions for children 0- 17 years of age of vaccine-preventable diseases during 2008-2013 at Astrid Lindgren Children's Hospi...

Background: Children undergoing cancer therapy are at risk for infectious complications that require hospitalization and antimicrobial therapy. Host factors such as age and underlying disease may predict the risk of severe infections in these children. To describe the increased morbidity due to infections in children with cancer, we characterized...

The national Swedish immunisation programme includes vaccine against diphtheria, tetanus, polio, pertussis, Haemophilus influenzae type B, Pneumococcus as well as measles, mumps and rubella. Data were collected on hospital admissions for children 0- 17 years of age of vaccine-preventable diseases during 2008-2013 at Astrid Lindgren Children’s Hospi...

Background: Pediatric community-acquired pneumonia (CAP) is a leading cause of childhood mortality in developing countries. In resource-poor settings, pneumonia diagnosis is commonly made clinically, based on World Health Organization guidelines, where breathing difficulty or cough and age-adjusted tachypnea suffice to establish diagnosis. Also, t...

Background: Limited literature suggests that cytokines/chemokines in childhood pneumonia could be potential biomarkers of disease severity, etiology or outcome. Objective: To measure a panel of cytokines/chemokines in children with community acquired pneumonia at presentation, and evaluate their relationship to etiology, clinical severity, total l...

Bacterial meningitis is an infection of the meninges and common aetiologies include Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. The incidence of meningitis has decreased in the industrialised world, with the introduction of the Haemophilus influenzae type B and Streptococcus pneumoniae vaccines. However, bacterial m...

Background: Childhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Com...

T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied. The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretrovi...

AimThis study explored the incidence and aetiology of bloodstream infections after patients received the pneumococcal conjugate vaccination and a risk-based intrapartum antibiotic prophylaxis against early onset sepsis caused by group B streptococcus. We also monitored clinically relevant antimicrobial resistance.Method We studied 3,986 positive bl...

- Copyright © 2014, Ferrata Storti Foundation.

Induction of protective immunity in infants has the potential to reduce morbidity and mortality in childhood infections but it has long been known that long-lasting protective immunity is difficult to induce in the neonate. This chapter describe the basis of the neonatal adaptive immune system. It also gives an update on current childhood immunisat...

The relevance of CD4+T-cells, viral load and age in the immunological response to influenza infection and vaccination in HIV-1 infected individuals has previously been pointed out. Our study aimed at assessing, in the setting of 2009 A(H1N1)pdm09 influenza vaccination, whether quantification of activation-induced deaminase (AID) expression in blood...

The persistence of antigen-specific memory B-cells (MBCs) in children and young adults long time after vaccination against measles, mumps and rubella (MMR) is not known. Here we have looked at the Swedish immunization program and examined children of 1-10 years after the first MMR dose in early childhood, as well as young adults of 7-18 years after...

Aim: To study the aetiology of bloodstream infections (BSI) in children 0-17 years, the influence of age and underlying co-morbidity on BSI rate, distribution of pathogens and outcome; and to provide data on antimicrobial susceptibility patterns. Methods: A retrospective population-based study. Data on blood cultures were collected at yearly int...

During foetal development, neonatal period and childhood, the immune system is constantly maturing. In the foetus, infection responsiveness is low and associates with spontaneous abortion. During the neonatal period, the infection response shifts towards a more pro-inflammatory response. The immune system of the newborn acquires adaptive features a...

High levels of soluble CD27 (sCD27), a marker of immune activation, are found in several infectious [including human immunodeficiency virus type-I (HIV-1)] and autoimmune diseases; however, a direct biological effect of sCD27 on B cells has not been established. The aim of this study was to investigate whether sCD27, by binding to CD70, can induce...

One important pathogenic feature of human immunodeficiency virus (HIV)-1 infection is chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells was reported to occur in both children and adults infected with HIV-1; these cells are responsible for maintaining an adequate serological response to antigens pr...

We have previously shown that factors secreted by activated CTLs induce apoptosis in a panel of glioblastoma lines. In this study, we analyzed the expression of death receptors, activation of caspases and mRNA expression of 96 apoptotic genes in glioblastoma lines either sensitive or resistant to supernatant of activated CTLs. Our results indicate...

To characterize the level of immature-transitional B-cells in blood during pediatric HIV-1 infection in relation to active or suppressed viremia. We also aimed at characterizing the level of expression of CXCR4, CXCR5 and CCR7 on immature-transitional B-cells, as these receptors are important mediators for homing of B-cells. Forty-eight HIV-1 verti...

Although HIV-1 infection does not directly target B cells, B-cell numbers are reduced and their function is impaired during HIV infection. Antibody titres against antigens previously encountered through vaccination or natural infection are low in patients with HIV. Intrinsic B-cell defects might be involved in the impairment of humoral immunity dur...

Chemokines and chemokine receptors are likely to play important roles in the pathogenesis of Epstein-Barr virus (EBV) -associated disease. The primary EBV infection occurs in the oropharynx where the virus infects mainly tonsillar B cells. We have previously shown that CXCR4 expression on tonsillar B cells is modulated by EBV. Here, CXCR5 and CCR7...

HIV-1 infection induces a progressive disruption of the B cell compartment impairing long-term immune responses to routine immunizations. Depletion of specific memory B cell pools occurs during the 1st stages of the infection and cannot be reestablished by antiretroviral treatment. We reasoned that an early control of viral replication through trea...

Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may...

HIV-1 infection is associated with B-cell abnormalities, such as hypergammaglobulinemia, poor immunization responses, and loss of serologic memory. To determine whether altered expression of chemokine receptors and their ligands may play a role in B-cell dysfunctions during HIV-1 infection, the expression of CXC chemokine receptor 4 (CXCR4), CXCR5,...

Induction of broad HIV-1 neutralizing antibodies should be a major goal of an effective HIV-1 vaccine. However, B cells are severely damaged during HIV-1 infection with loss of memory B cells and decline of serological memory. The molecular events leading to B cell damage must be further characterized with the aim of selecting vaccine components al...

CXCL12 (SDF-1alpha) is a chemokine, which plays an important role in normal B-cell lymphopoesis, migration and homing to the bone marrow (BM) and previous studies have suggested a role for CXCL12 and its receptor CXCR4 in the pathogenesis of ALL. CXCL12 levels in serum were evaluated from ALL-children and controls. The biological effect of recombin...

Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI a...

Circulating memory B cells are severely reduced in the peripheral blood of HIV-1-infected patients. We investigated whether dysfunctional serologic memory to non-HIV antigens is related to disease progression by evaluating the frequency of memory B cells, plasma IgG, plasma levels of antibodies to measles, and Streptococcus pneumoniae, and enumerat...

The primary Epstein-Barr virus (EBV) infection occurs in the oropharynx, where the virus infects B cells and subsequently establishes latency in the memory B-cell compartment. EBV has previously been shown to induce changes in the cell surface expression of several chemokine receptors in cell lines and the transfection of EBNA2 or LMP1 into a B-cel...

CD27, a member of the TNF receptor family, plays an important role in lymphoid proliferation, differentiation and apoptosis. This study addresses the expression of CD27 and its ligand, CD70, in children with acute lymphoblastic leukemia (ALL) and the possible role of this receptor-ligand pair in the pathogenesis of ALL. Expression of CD27 and CD70...

Hypergammaglobulinemia and defective humoral immunity are hallmarks of HIV-1 infection. Naive B cells have been recently suggested as the major source of hypergammaglobulinemia in chronic viral infections. We recently reported that HIV-1-infected patients carry low levels of memory B cells. Here we studied whether defects in the naive and memory B...

HIV-1 genetic subtypes might have a different impact on disease progression and response to antiretroviral therapy (ART). Few data are available on the immune activation profile in patients with different HIV-1 subtypes. We have tested by ELISA the plasma levels of an immune activation marker, soluble CD27 (sCD27), in a cohort of 64 patients infect...

Nerve growth factor (NGF) regulates B cell activation and differentiation and is an autocrine survival factor for memory B lymphocytes. We have reported recently that the number of memory B cells is reduced during HIV-1 infection. In this study we evaluated whether alteration in the NGF supply was involved in memory B cell loss in HIV-1-infected su...

To evaluate viral vaccination immunity and booster responses in children treated successfully for acute lymphoblastic leukemia by chemotherapy and to study the response to treatment of antibody-producing plasma cells that are important for persistence of humoral immunity. Forty-three children who were in continuous first remission for a median of 5...