Publications by authors named "Marketa Bloomfield"

Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment.

View Article and Find Full Text PDF

Background: Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only 8 documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1.

Objective: We comprehensively reviewed clinical and immunologic findings of patients with B-cell deficiency attributed to variants in IGLL1.

View Article and Find Full Text PDF

The balance between the tumor-necrosis factor α (TNFα) and type-I interferon (T1IFN) pathways is crucial for proper immune function. Dysregulation of either pathway can contribute to autoimmune diseases development. Even though TNFα blockade has shown promising results in various autoimmune diseases, the effect on the balance between TNFα and T1IFN is elusive.

View Article and Find Full Text PDF
Article Synopsis
  • Inborn errors of immunity (IEI) with dysregulated JAK/STAT signaling can lead to immune dysfunction and infections, and while hematopoietic stem cell transplantation (HSCT) is a potential cure, initial outcomes were not promising.
  • This study evaluated the effectiveness of off-label JAK inhibitors (JAKi) as a treatment option for patients with hyperactive JAK/STAT signaling disorders at various European medical centers.
  • Results showed that 87% of patients with STAT1 gain of function and 90% with STAT3 gain of function saw symptom improvement, with mild adverse events reported; a significant portion of patients continued JAKi treatment successfully, and some proceeded to HSCT, achieving a 91%
View Article and Find Full Text PDF

Introduction: Juvenile idiopathic arthritis (JIA), a clinically variable disease characterized by autoimmune arthritis, affects children, and its immunopathology remains elusive. Alterations in neutrophil biology play an important role in this disease. In the present study, we aimed to explore the features of low-density neutrophils (LDNs) in patients with JIA.

View Article and Find Full Text PDF
Article Synopsis
  • Multisystem inflammatory syndrome in children (MIS-C) is a severe condition that can occur weeks after a COVID-19 infection, characterized by intense inflammation and immune response.
  • In a study of MIS-C patients, researchers found increased levels of IFN-γ and BAFF, while the presence of certain autoantibodies indicated potential autoimmune links similar to systemic lupus erythematosus (SLE).
  • The findings suggest that changes in B cell behavior and elevated BAFF may play a significant role in the immune response seen in MIS-C, pointing to possible connections with autoimmune disorders.
View Article and Find Full Text PDF

Background: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.

Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.

View Article and Find Full Text PDF
Article Synopsis
  • STAT1 gain-of-function mutations lead to an immune disorder characterized by symptoms ranging from chronic mucocutaneous candidiasis to serious issues like autoimmunity and vascular problems, primarily due to Th17 cell dysfunction.
  • A study of ten patients found that their peripheral blood neutrophils were immature, highly activated, and showed unusual behaviors such as increased degranulation, NETosis, and inflammatory responses, but did not behave like typical immune cells when stimulated.
  • The treatment with JAKinib ruxolitinib did not improve the neutrophil abnormalities, indicating that these cells might play a significant role in the immune issues associated with STAT1 GOF CMC.
View Article and Find Full Text PDF
Article Synopsis
  • The field of immunology has seen significant advancements in recent decades, particularly highlighted by rapid progress in understanding the immune system since the start of the millennium.
  • The COVID-19 pandemic in 2020 accelerated research, leading to important developments like effective vaccines against the SARS-CoV-2 virus, showcasing the practical application of immunological knowledge.
  • Ongoing advancements in immunopathology cover crucial areas including allergies, immunodeficiency, immunity and infection, vaccination, autoimmune diseases, and cancer immunology, with contributions from cutting-edge technologies like AI and advanced mathematics.
View Article and Find Full Text PDF
Article Synopsis
  • Multisystem inflammatory syndrome in children (MIS-C) is a serious condition linked to COVID-19, developing around 4 weeks after infection, characterized by hyperinflammation and potential shock.* -
  • The European Academy of Allergy and Clinical Immunology formed a task force to create guidelines for diagnosing, treating, and monitoring MIS-C, focusing on its unclear immunological mechanisms.* -
  • Current treatment involves supportive care and immunosuppressive agents like steroids, and regular follow-ups are essential to monitor for complications, with vaccination against COVID-19 shown to help prevent MIS-C.*
View Article and Find Full Text PDF

Objectives: To evaluate the efficacy of presepsin (P-SEP) as a potential biomarker of early-onset neonatal sepsis (EOS) and compare it to other routinely used markers of inflammation. To establish the cut-off values of P-SEP for EOS.

Study Design: 184 newborns were prospectively recruited between January 2018 to December 2020.

View Article and Find Full Text PDF

STAT1 gain-of-function (GOF) mutations underlie an inborn error of immunity hallmarked by chronic mucocutaneous candidiasis (CMC). Beyond the fungal susceptibility, attributed to Th17 failure, over half of the reported patients suffer from autoimmune manifestations, mechanism of which has not been explained yet. We hypothesized that the STAT1 mutations would affect dendritic cells' (DCs) properties and alter their inflammatory and tolerogenic functions.

View Article and Find Full Text PDF

Patients with STAT1 gain-of-function (GOF) mutations suffer from an inborn error of immunity hallmarked by chronic mucocutaneous candidiasis (CMC). The pathogenesis behind this complex and heterogeneous disease is still incompletely understood. Beyond the well-recognized Th17 failure, linked to the STAT1/STAT3 dysbalance-driven abrogation of antifungal defense, only little is known about the consequences of augmented STAT1 signaling in other cells, including, interestingly, the innate immune cells.

View Article and Find Full Text PDF

Background: Inborn errors of IL-12/IL-23-IFNγ immunity underlie Mendelian susceptibility to mycobacterial diseases (MSMD), a group of immunodeficiencies characterized by a highly selective susceptibility to weakly virulent strains of mycobacteria, such as non-tuberculous mycobacteria (NTM) and bacillus Calmette-Guérin (BCG). Cutaneous mycobacterial infections are common in MSMD and may represent a red flag for this immunodeficiency.

Objectives: We present a case series of four paediatric patients with MSMD, specifically with IFNγR1 and STAT1 deficiencies, and cutaneous NTM/BCG infections to increase awareness of this immunodeficiency, which may, in some cases, be intercepted by the dermatologist and thus timely referred to the immunologist.

View Article and Find Full Text PDF

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course.

View Article and Find Full Text PDF
Article Synopsis
  • A study explored the effects of JAK inhibitors (JAKinibs) on pediatric patients with STAT1 gain of function (GOF) mutations, which are linked to severe immune issues and infections.
  • The research involved 10 children treated with JAKinibs, showing significant clinical improvement in most, with reduced immune deficiency scores during therapy.
  • Although results are promising, there is a need for standardized guidelines on the use of JAKinibs, including dosing and monitoring, to optimize their benefits for these patients.
View Article and Find Full Text PDF

Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire.

View Article and Find Full Text PDF

Our study presents a novel germline c.1715G>T (p.G572V) mutation in the gene encoding Toll-like receptor 8 (TLR8) causing an autoimmune and autoinflammatory disorder in a family with monozygotic male twins, who suffer from severe autoimmune hemolytic anemia worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis, and CNS vasculitis.

View Article and Find Full Text PDF

Purpose: 22q11.2 deletion syndrome (22q11.2DS) is a primary immunodeficiency characterized chiefly by the hypoplasia of the thymus resulting in T cell lymphopenia, increased susceptibility to infections, and higher risk of autoimmune diseases.

View Article and Find Full Text PDF
Article Synopsis
  • - Activated phosphoinositide 3-kinase delta syndrome (APDS) is an immunodeficiency condition, primarily due to mutations in specific PI3K subunits, leading to issues in both humoral and cellular immunity, and resembling other immunodeficiencies like hyper-IgM syndromes and CVID.
  • - A study examined eight APDS patients, highlighting early warning signs, symptom progression, variations among individuals, and their reactions to treatments, with common issues including recurrent infections, gastrointestinal problems, and autoimmune conditions.
  • - Findings showed that while all patients reacted well to immunoglobulin replacement therapy, only partial success was seen with mTOR inhibitors; however, the specific PI3K inhibitor leniolis
View Article and Find Full Text PDF

We present a case of a 42-year-old woman with Mendelian susceptibility to mycobacterial disease. The disease was diagnosed at an adult age with relatively typical clinical manifestations; the skeleton, joints, and soft tissues were affected by nontuberculous mycobacteria: , , and . A previously published loss-of-function and functionally validated variant NM_000416.

View Article and Find Full Text PDF

During the COVID-19 pandemics of 2020, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both adults and children were shown to mount a specific antibody response to the virus. As infected children often exhibit mild symptoms or even remain asymptomatic, they are likely to be under tested for the direct presence of the virus. Mapping the SARS-CoV-2 antibodies frequency informs more accurately on the disease prevalence and helps guide the protective and therapeutic strategies.

View Article and Find Full Text PDF