Publications by authors named "Angela Deya Martinez"
Article Synopsis
- A phase 3 trial was conducted to evaluate the efficacy and safety of mavorixafor, an oral medication, in individuals with WHIM syndrome, a rare immunodeficiency disorder caused by genetic mutations.
- Participants were randomly assigned to receive either mavorixafor or a placebo for 52 weeks, with the study focusing on the time above certain white blood cell counts as the primary endpoint.
- Results showed mavorixafor significantly increased white blood cell counts, reduced infection rates and severity, and was well tolerated without serious adverse events occurring during the study.
Article Synopsis
- The study highlights the challenges in interpreting diagnostic results for inborn errors of immunity due to the absence of age-specific reference values for Tregs in children and a lack of consensus on Treg immunophenotypes.
- The researchers compared three definitions of Tregs and examined the frequencies and maturation status of both Tregs and Bregs in a sample of 55 healthy pediatric controls.
- Findings showed significant variability in Treg numbers based on the definition used, a positive correlation between the definitions, and a trend of declining Treg and Breg frequencies as children age, with Breg maturation occurring earlier than Tregs.
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%
Second-line treatments of autoimmune cytopenias (AC) are not well-defined in children. Mycophenolate mofetil (MMF) is an immunosuppressant agent that has been demonstrated to be safe and effective in this setting. A retrospective observational study was conducted in 18 children with prolonged AC who received MMF, in order to describe clinical and biological markers of response.
View Article and Find Full Text PDFBackground: Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown.
View Article and Find Full Text PDFArticle Synopsis
- Patients with X-linked recessive deficiency of TLR7, a crucial immune sensor, struggle to recognize SARS-CoV-2 and produce necessary type I interferons, leading to severe pneumonia cases.
- A study included 22 unvaccinated individuals with MyD88 or IRAK-4 deficiencies from multiple countries, primarily affecting children and young adults, with a significant portion requiring hospitalization.
- The findings highlight that these genetic deficiencies, previously linked to bacterial infections, also significantly increase vulnerability to hypoxemic pneumonia caused by COVID-19, especially as patients age.
Expected impact of immunomodulatory agents during pregnancy: A newborn's perspective.
Pediatr Allergy Immunol
February 2023
Article Synopsis
- The neonatal immune development starts during pregnancy to prepare babies for life outside the womb, focusing on non-inflammatory immune responses to promote tolerance.
- Newborns have heightened Th17/Th22 responses for better protection against fungi and mucosal threats.
- There’s growing interest in how immune-modulating drugs taken during pregnancy affect fetal immune development, highlighting the need for more research on their long-term impacts on newborn immune health.
Purpose: To describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC).
Methods: Unvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months.
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is a T-cell hyperactivation disorder that can manifest with both immunodeficiency and immune dysregulation. Approximately one-third of patients may present mild symptoms and remain stable under supportive care. The remaining patients may develop severe multiorgan autoimmunity requiring lifelong immunosuppressive treatment.
View Article and Find Full Text PDFUnlabelled: The presence of active viral infections has an impact on the prognosis of patients undergoing hematopoietic stem cell transplantation (HSCT). Nevertheless, the number of reports of cytomegalovirus infection in patients with inborn errors of immunity (IEI) who undergo HSCT is relatively low. To analyze the effect of cytomegalovirus infection acquired prior to curative treatment on patient survival in 123 children with IEI.
View Article and Find Full Text PDFArticle 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.
Article Synopsis
- Autosomal recessive (AR) STAT1 deficiency significantly impairs the immune response to various infections, making patients highly susceptible to viral and mycobacterial diseases.
- An international study of 32 patients revealed that complete deficiency leads to more severe outcomes, including a higher mortality rate and serious reactions to vaccines.
- Hematopoietic stem cell transplantation shows promise as a treatment, with a 64% survival rate for those who undergo the procedure, underscoring the importance of early diagnosis and differentiation between complete and partial deficiency forms.
Article Synopsis
- Chronic mucocutaneous candidiasis (CMC) involves persistent non-invasive fungal infections affecting the skin, nails, and mucous membranes, often accompanied by autoimmune issues due to immune system defects.
- The main immune problem is related to cytokine IL-17 signaling disruptions, frequently caused by gene mutations that enhance its activity.
- Effective treatment typically starts with azole antifungals, but drug resistance is a challenge; identifying genetic defects can help expand treatment options, including using Type I and II inhibitors to manage CMC linked to specific mutations.
Background: Phosphoglucomutase-3 (PGM3) deficiency is a congenital disorder of glycosylation (CDG) with hyperimmunoglobulin IgE, atopy, and a variable immunological phenotype; most reported patients display dysmorphic features. The aim of the study was to characterize the genotype and phenotype of individuals with newly identified compound heterozygous variants in the phosphate-binding domain of PGM3 in order to better understand phenotypic differences between these patients and published cases.
Methods: We analyzed PGM3 protein expression, PGM3 enzymatic activity, the presence of other gene variants within the N-glycosylation pathway, and the clinical and immunological manifestations of two affected siblings.
Article Synopsis
- Post-hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) occurred in 9% of the studied 502 children with primary immunodeficiency, typically developing around 6.5 months after the transplant.
- Key risk factors included pre-existing AIC, mismatched donors, and the use of alemtuzumab, which was independently linked to increased risk.
- Treatments yielded positive outcomes, with 50% remission from corticosteroids and intravenous immunoglobulin, while improvements in survival rates were noted after 2011, with 87% of survivors achieving complete remission over a median follow-up of 5.8 years.
Single-cycle rituximab-induced immunologic changes in children: Enhanced in neuroimmunologic disease?
Neurol Neuroimmunol Neuroinflamm
July 2020
Objective: To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines.
Methods: Retrospective study of immunologic changes in children (aged ≤18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency.
Article Synopsis
- An increasing number of NFKB1 variants have been linked to diverse immune system issues in patients, prompting a comprehensive study of these mutations.
- The study evaluated 231 individuals with various NFKB1 mutations, identifying 56 as pathogenic, resulting in primary immunodeficiency and other immune-related problems like autoimmunity and malignancy.
- The findings highlight the need for awareness among medical professionals about this condition's complexity, recommending treatments like immunoglobulin replacement, immunosuppressants, and considering stem cell transplantation.
Neonatal thymectomy in children-accelerating the immunologic clock?
J Allergy Clin Immunol
August 2020
The thymus is critical for central tolerance and diverse T-lymphocyte repertoire development, to provide lifelong defense against pathogens while maintaining self-tolerance. Peak thymic output occurs in utero, during infancy, and in early childhood, diminishing throughout life. Infants with congenital heart disease requiring sternotomy often undergo thymectomy to clear the surgical field.
View Article and Find Full Text PDFToll-like receptor 3 deficiency in autoimmune encephalitis post-herpes simplex encephalitis.
Neurol Neuroimmunol Neuroinflamm
November 2019
Purpose: Mendelian suceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency predisposing to severe disease caused by mycobacteria and other intracellular pathogens. Delay in diagnosis can have an impact on the patient's prognosis.
Methods: We evaluated the IFN-γ circuit by studying IFN-γ production after mycobacterial challenge as well as IL-12Rβ1 expression and STAT4 phosphorylation in response to IL-12p70 stimulation in whole blood of a 6-year-old Peruvian girl with disseminated recurrent mycobacterial infection diagnosed as multidrug-resistant tuberculosis.
Pregnancy and early infancy represent two very particular immunological states. During pregnancy, the haploidentical fetus and the pregnant women develop tolerance mechanisms to avoid rejection; then, just after birth, the neonatal immune system must modulate the transition from the virtually sterile but haploidentical uterus to a world full of antigens and the rapid microbial colonization of the mucosa. B regulatory (Breg) cells are a recently discovered B cell subset thought to play a pivotal role in different conditions such as chronic infections, autoimmunity, cancer, and transplantation among others in addition to pregnancy.
View Article and Find Full Text PDF