Leopoldo Santos-Argumedo

• PhD
• P.I. at Center for Research and Advanced Studies of the National Polytechnic Institute

Background/Objectives: B-cell acute lymphoblastic leukemia (B-ALL) presents a challenge in hematological malignancies due to its heterogeneity, which impacts treatment outcomes. Stratification based on the DNA index (DNAi) categorizes patients into favorable prognosis (hyperploid), standard prognosis (normoploid), and uncertain or poor prognosis (h...

Background: During the COVID-19 pandemic, identifying reliable biomarkers for predicting disease severity and patient outcomes in unvaccinated individuals is essential. This study evaluates the efficacy of key hematological markers, including leukocyte and neutrophil counts, Neutrophil-to-Lymphocyte Ratio (NLR), and cytokine profiles (IL-6, INF-γ,...

Introduction Lipopolysaccharide-responsive and beige-like anchor (LRBA) is a scaffolding protein that interacts with proteins such as CTLA-4 and PKA, the importance of which has been determined in various cell types, including T regulatory cells, B cells, and renal cells. LRBA deficiency is associated with an inborn error in immunity characterized...

LRBA is a cytoplasmic protein that is ubiquitously distributed. Almost all LRBA domains have a scaffolding function. In 2012, it was reported that homozygous variants in LRBA are associated with early‐onset hypogammaglobulinemia. Since its discovery, more than 100 pathogenic variants have been reported. This review focuses on the variants reported...

Introduction Lrba is a cytoplasmic protein involved in vesicular trafficking. Lrba-deficient (Lrba-/-) mice exhibit substantially higher levels of IgA in both serum and feces than wild-type (WT) mice. Transforming growth factor β1 (TGFβ1) and its receptors (TGFβR I and II) is essential for differentiating IgA+ B cells. Furthermore, increased IgA pr...

Colostrum, the first milk secretion, is characterized by a high concentration of immunologically active molecules with neutralizing and antibacterial capabilities. Mycobacterium tuberculosis is a microorganism primarily infecting the lungs but can also affect non-pulmonary tissues. Despite a BCG vaccination coverage exceeding 97% in Mexico, pulmona...

Lipopolysaccharide-Responsive Beige-like anchor (LRBA) is a scaffolding protein whose deficiency is associated with an inborn error of immunity error like common variable immunodeficiency. Patients with LRBA deficiency have a heterogeneous clinical presentation including hypogammaglobulinemia, reduction of B and T regulatory cells, recurrent infect...

γδT intraepithelial lymphocyte represents up to 60% of the small intestine intraepithelial compartment. They are highly migrating cells and constantly interact with the epithelial cell layer and lamina propria cells. This migratory phenotype is related to the homeostasis of the small intestine, the control of bacterial and parasitic infections, and...

Cyclic AMP-dependent protein kinase A (PKA) is a ubiquitous enzymatic complex that is involved in a broad spectrum of intracellular receptor signaling. The activity of PKA depends on A-kinase anchoring proteins (AKAPs) that attach to PKAs close to their substrates to control signaling. Although the relevance of PKA-AKAP signaling in the immune syst...

γδT intraepithelial lymphocyte represents up to 60% of the small intestine intraepithelial compartment. They are highly migrating cells and constantly interact with the epithelial cell layer and lamina propria cells. This migratory phenotype is related to the homeostasis of the small intestine, the control of bacterial and parasitic infections, and...

The current pandemic generated by SARS-CoV-2 has led to mass vaccination with different biologics that have shown wide variations among human populations according to the origin and formulation of the vaccine. Studies evaluating the response in individuals with a natural infection before vaccination have been limited to antibody titer analysis and...

Methods Primary mouse spleen B cells were stimulated or not with LPS (10ug/ml) + IL-4 (10IU/ml) for 48 hours. Two million cells were infected 72 h with MNV-1 at a MOI of 5. The non-structural (NS7) viral protein expression was analyzed in cell lysates by Western blot with a specific anti-NS7 antibody. The supernatant-associated virus in Raw 264.7 c...

Background Common Variable Immunodeficiency (CVID) is a heterogeneous disorder characterized by defective B cell differentiation and antibody production. Interleukin (IL)-21 activates STAT3, a potent regulator of B cell differentiation into plasma cells. We have studied the phosphorylation of STAT3 in CVID patients and its contribution to B cells s...

NK cells are contained in the ILC1 group; they are recognized for their antiviral and antitumor cytotoxic capacity; NK cells also participate in other immune response processes through cytokines secretion. However, the mechanisms that regulate these functions are poorly understood since NK cells are not as abundant as other lymphocytes, which has m...

CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38⁺CD25⁺ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested tha...

Microbiota acquired during labor and through the first days of life contributes to the newborn’s immune maturation and development. Mother provides probiotics and prebiotics factors through colostrum and maternal milk to shape the first neonatal microbiota. Previous works have reported that immunoglobulin A (IgA) secreted in colostrum is coating a...

List of Rab35 (S22N)-interacting proteins in samples from Raw 264.7 macrophages.

It was built using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins; http://www. string-db.org). The PPI was generated with confidence score ≥ 0.4. The network contains 39 nodes and 78 edges. Likewise, grouping of Rab35-S22N -interacting proteins into biological processes was carried out using Gene Ontology (GO) annotation (http:...

Cell spreading and phagocytosis are notably regulated by small GTPases and GAP proteins. TBC1D10C is a dual inhibitory protein with GAP activity. In immune cells, TBC1D10C is one of the elements regulating lymphocyte activation. However, its specific role in macrophages remains unknown. Here, we show that TBC1D10C engages in functions dependent on...

The coronavirus disease 2019 (COVID-19) pandemic has reached an unprecedented level. There is a strong demand for diagnostic and serological supplies worldwide, making it necessary for countries to establish their own technologies to produce high-quality biomolecules. The two main viral antigens used for the diagnostics for severe acute respiratory...

Helicobacter pylori is a gram-negative bacterium found on the luminal surface of the gastric mucosa in at least 50% of the world's human population. The protective effect of breastfeeding against H. pylori infection has been extensively reported; however, the mechanisms behind this protection remain poorly understood. Human IgA from colostrum has r...

Background: Microbiota colonization during labor and through the first meals contributes to immune maturation and development of the newborn. Mother provides probiotics and prebiotics factors through colostrum and maternal milk to shape the first neonatal microbiota. Previous works have reported that immunoglobulin A (IgA) secreted in colostrum is...

Cell migration is a dynamic process that involves adhesion molecules and the deformation of the moving cell that depends on cytoskeletal remodeling and actin-modulating proteins such as myosins. In this work, we analyzed the role of the class I Myosin-1 g (Myo1g) in migratory processes of LPS + IL-4 activated B lymphocytes in vivo and in vitro. In...

[This corrects the article DOI: 10.1155/2019/6357256.].

During immune responses, B cells home to lymph nodes (LNs), where they encounter antigens. Homing starts with capture and L-selectin-dependent rolling on the activated endothelium of high endothelial venules (HEV). After recognition of chemokines presented on HEV, activation of B cell integrins occurs mediating firm arrest. Subsequently, B cells cr...

Dengue virus infection (DENV-2) is transmitted by infected mosquitoes via the skin, where many dermal and epidermal cells are potentially susceptible to infection. Most of the cells in an area of infection will establish an antiviral microenvironment to control viral replication. Although cumulative studies report permissive DENV-2 infection in den...

Antecedentes: Las deficiencias de anticuerpos abarcan un amplio espectro de patologías y constituyen aproximadamente 50 % de las inmunodeficiencias primarias; con la citometría es posible evaluar el estado inmunológico de forma rápida, efectiva y a bajo costo. Objetivo: Evaluar mediante citometría de flujo, las células de pacientes con tres tipos...

Background: Antibody deficiencies encompass a wide spectrum of pathologies and constitute approximately 50 % of primary immunodeficiencies; with cytometry, it is possible to evaluate the immune status rapidly, effectively and at low cost. Objective: To assess, by means of flow cytometry, the cells of patients with three types of primary humoral...

Lipopolysaccharide (LPS)‐responsive beige‐like anchor (LRBA) protein was initially described as a monogenetic cause for Common Variable Immune Deficiency, a syndrome characterized by low levels of B‐cells, defects in memory B‐cell differentiation, and hypogammaglobulinemia. LRBA was identified as an LPS‐up‐regulated gene in B‐cells, macrophages, an...

Background: Several studies have evaluated the effect of infectious diseases and vaccine protocols during pregnancy on maternal milk immunoglobulin (Ig) levels, to understand the protection conferred by lactation on newborns. Colostrum is the primary source of maternal IgA for the newborn. IgA participates in protection mechanisms in the neonate's...

B lymphocytes are a leukocyte subset capable of developing several functions apart from differentiating into antibody‐secreting cells. These processes are triggered by external activation signals that induce changes in the plasma membrane properties, regulated by the formation of different lipid‐bilayer subdomains that are associated with the under...

The inclusion of lymphocytes in high endothelium venules and their migration to the lymph nodes are critical steps in immune response. Cell migration is regulated by actin cytoskeleton and myosins. Myo1e is a long-tailed class I myosin and is highly expressed in B cells that have not been studied in the context of cell migration. By using intravita...

Significance Myosin1e is a protein regulating actin cytoskeleton functions, which has not been studied in the context of neutrophil recruitment during inflammation. Using intravital microscopy of inflamed tissue in WT and myosin1e-deficient mice, we show that absence of myosin1e inhibits neutrophil migration out of the blood stream into inflamed ti...

Most patients with ectodermal dysplasia-immunodeficiency (ED-ID) or incontinentia pigmenti (IP) harbor hemizygous/hypomorphic mutations in the IKBKG gene which encodes the protein NEMO

The autosomal dominant form of hyper IgE syndrome (HIES) has both immunologic and non-immunologic features

Zika virus (ZIKV), an emerging mosquito-borne flavivirus, has quickly spread in many regions around the world where dengue virus (DENV) is endemic. This represents a major health concern, given the high homology between these two viruses, which can result in cross-reactivity. The aim of this study was to determine the cross-reacting antibody respon...

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by elevated levels of immunoglobulin E (IgE), eczematous dermatitis, cold abscesses, and recurrent infections of the lung and skin caused by Staphylococcus aureus . The dominant form is characterized by nonimmunologic features including skeletal, connective tissue, and pulmo...

The recruitment of leukocyte to high endothelium venules and their migration to the lymph nodes are critical steps to initiate an immune response. Cell migration is regulated by the actin cytoskeleton where myosins have a very import role. Myo1e is a long tail class I myosin highly expressed in B cells that not have been studied in the context of c...

Background: Colostrum is the primary source of maternal immunoglobulin A (IgA) for the newborn. IgA participates in protection and regulation mechanisms of the immune response at the neonate's mucosa. Several studies have evaluated infectious diseases and vaccine protocols effects during pregnancy on maternal milk IgA levels, with the aim to under...

Background: Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies defined by marked reductions in serum IgG, IgA and/or IgM levels and recurrent bacterial infections. Some patients are associated with defects in T cells and regulatory T cells (Tregs), resulting in recurrent viral infections and early-ons...

The cytotoxin-associated gen A (CagA) is an oncogenic virulence factor of Helicobacter pylori that is related with the development of gastric cancer and gastric MALToma: a B cell non-Hodgkin’s lymphoma. CagA has an important role in the development of cancer due to its promiscuous interaction with different signaling-mediators. The association of C...

Immunoglobulin A (IgA) is the main antibody isotype present in the body fluids such as tears, intestinal mucous, colostrum and saliva. There are two subtypes of IgA in humans: IgA1 mainly present in blood and IgA2, the preferentially expressed mucosal antibody. In clinical practice, immunoglobulins are typically measured in venous or capillary bloo...

SLE is an autoimmune disease which is characterized by the formation of auto-antibodies and loss of tolerance. In addition to the production of auto-antibodies, certain sub-populations of B cells may play a critical role in the resolution or severity of the disease. Recently, a novel CD11c+, CD21low, and T-bet+ expressing B-cell subset has been ide...

Connections established between cytoskeleton and plasma membrane are essential in cellular processes such as cell migration, vesicular trafficking, and cytokinesis. Class I myosins are motor proteins linking the actin‐cytoskeleton with membrane phospholipids. Previous studies have implicated these molecules in cell functions including endocytosis,...

Intestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhance its intercellular adhesion properties in order...

A novel cell population denominated IFN‐γ‐producing killer dendritic cells (IKDCs), has been recently described. These cells are lymphocytes lacking B‐ or T‐ receptors, but they can be identified by the presence of B220⁺ CD38⁺ CD49b⁺ and low CD11c, among other cell surface markers. The main characteristics of IKDCs are the production of IFN‐γ and t...

La microbiota humana es el conjunto de microorganismos que residen en nuestro cuerpo. Su composición filogenética está relacionada con el riesgo de padecer enfermedades inflamatorias y cuadros alérgicos. Los humanos interaccionamos con una gran cantidad y variedad de estos microorganismos a través de la piel y las mucosas. Un mecanismo de protecció...

The skin is the first anatomical region that dengue virus (DENV) encounters during the natural infection. Although the role of some skin resident cells like dendritic cells and fibroblasts has been demonstrated to be crucial to elucidate the role of resident cells and molecules participating during the early events of the innate immune response, th...

CD38 is a transmembrane protein expressed in B lymphocytes, that is able to induce responses as proliferation, differentiation or apoptosis. Several reports propose that CD38 deficiency accelerates autoimmune processes in murine models of autoimmune diabetes, lymphoproliferation, and rheumatoid arthritis. Other reports have shown elevated CD38 expr...

Naegleria fowleri is a protozoan that invades the central nervous system and causes primary amoebic meningoencephalitis. It has been reported that N. fowleri induces an important inflammatory response during the infection. In the present study, we evaluated the roles of Toll-like receptors in the recognition of N. fowleri trophozoites by human muco...

Cell migration and adhesion are critical for immune system function and involve many proteins, which must be continuously transported and recycled in the cell. Recycling of adhesion molecules requires the participation of several proteins, including actin, tubulin, and GTPases, and of membrane components such as sphingolipids and cholesterol. Howev...

Background: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton’s Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA...

Background Better knowledge of the innate immune system of insects will improve our understanding of mosquitoes as potential vectors of diverse pathogens. The ubiquitously expressed 14-3-3 protein family is evolutionarily conserved from yeast to mammals, and at least two isoforms of 14-3-3, the ε and ζ, have been identified in insects. These protei...

TSPAN33 is the last described member of the tetraspanin protein family; it is highly expressed in malignant B cells and is one of the most controversial tetraspanins on regard of its function in leukocytes. In human B cells, we observed that the expression of TSPAN33 is rapidly induced by IL-4 and anti-CD40 stimulation and its antibody-induced cros...

Tetraspanins are a family of transmembrane proteins that form membrane microdomains. They play important roles in migration, adhesion, and other cellular processes. TspanC8, a subfamily of tetraspanins, were found to associate and promote ADAM10 trafficking and cell surface localization. One of its members, Tspan33, is expressed in activated B cell...

Background: Peripheral blood B cells include lymphocytes at various stages of differentiation, each with a specific function in the immune response. All these stages show variations in percentage and absolute number throughout human life. The numbers and proportions of B subpopulation are influenced by factors such as gender, age, ethnicity, and l...

Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema, pneumonia, and high levels of serum IgE. Non-immunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined by the presence of two or m...

Haemophagocytic lymphohistiocytosis (HLH) may be triggered by infections with or without association with classical primary immunodeficiencies. Viruses are the most common triggers, however, many others microorganisms have been linked such as mycobacterial infection. We followed up on two patients previously reported with IL-12Rβ1 deficiency who de...

B-lymphocytes are migrating cells that specialize in antigen presentation, antibody secretion, and endocytosis; these processes implicate the modulation of plasma membrane elasticity. Cell stiffness is a force generated by the interaction between the actin-cytoskeleton and the plasma membrane, which requires the participation of several proteins. T...

X-linked agammaglobulinemia (XLA) is caused by BTK mutations, patients typically show < 2% of peripheral B cells and reduced levels of all immunoglobulins; they suffer from recurrent infections of bacterial origin; however, viral infections, autoimmune-like diseases, and an increased risk of developing gastric cancer are also reported. In this work...

For many years, it has been considered that the function of B cells is only to serve as precursors of antibody-producing plasma cells; however, this simplistic view has been challenged in the past thirty years. The first big surprise came during the seventies, when it was shown that B lymphocytes are not a homogeneous population, but is made up of...

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by B cell dysfunction and decreased serum immunoglobulin. CVID patients are classified by the absence or presence of memory B cells. In addition, T cell defects have been demonstrated in only a proportion of CVID patients. The aim of this study was to evaluate the f...

Hyper-IgE syndrome is an immunodeficiency disorder that is characterized by distinctive immunologic and non-immunologic manifestations. Although mutations in STAT3 have been associated with HIES, the exact nature of the relationship is unknown. Here, we characterized the functional activity of STAT3 and its mutations in eleven Mexican patients with...

We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9...

Tetraspanin 33 (Tspan33) is a transmembrane protein highly expressed in activated B cells. Tspan33 is a member of the tetraspanin family, which is characterized by conserved domains and functions. Tetraspanins provide a scaffold for the formation of membrane microdomains, called Tetraspanin Enriched Microdomains. Other members of this family have b...

CVID is one of the most common primary immunodeficiency diseases and is a diagnosis of exclusion. CVID is characterized by hypogammaglobulinemia and recurrent bacterial infections. About two third of CVID subjects have an autoimmune condition. The etiology of about 80% of CVID remains unknown. Genetic linkage studies in such families have found dis...

The X-linked hyper-IgM syndrome (XHIGM) is the most common form of HIGM. Patients are clinically diagnosed on the basis of recurrent sinopulmonary infections, accompanied with low levels of IgG and IgA, normal to elevated levels of IgM, and the presence of peripheral B cells. Here, we have reported a novel deletion of four nucleotides in CD40LG exo...

Bruton’s tyrosine kinase (BTK) is a well-studied molecule that is known to play a critical role in pre-B and B cell receptor signaling. It is crucial for early B cell development in the bone marrow and for B cell activation and differentiation in peripheral lymphoid organs. In addition to its role in B cell development and function, BTK is also exp...

Two patients with a severe leukocyte adhesion deficiency type 1 (LAD-1) phenotype were analyzed by flow cytometry and functional assays to demonstrate the improper adhesive and phagocytic responses of their leukocytes. A single homozygous defect that involves a missense mutation (c.817G>A) that encodes for a G273R substitution in CD18 was identifie...

CD38 is a 45-kD transmembrane protein that is expressed in immature and mature lymphocytes. However, the expression and function of CD38 during B cell differentiation in mice is poorly understood. Here, we report that CD38 is expressed from the earliest stages of B cell development. Pre-pro-B, pro-B, pre-B, and immature B cells from murine bone mar...

Background: There are two inheritance patterns, the X-linked recessive (XL) pattern and the autosomal recessive pattern. There is no information on the predominant inheritance pattern of male patients with chronic granulomatous disease (CGD) in Mexico. Objective: The aim of this study was to determine the inheritance pattern in a cohort of Mexic...

Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry w...

Since 1996, several studies characterizing the association between primary immunodeficiencies and susceptibility to infections with environmental and non-pathogenic mycobacteria such as the Bacillus Calmette-Guérin (Mycobacterium bovis Bacillus of Calmette Guérin strain) as well as disseminated infections by Salmonella spp. have been conducted. The...

Review of the growing evidence indicating the importance of Btk in innate immune responses aside from its role in humoral immunity. Btk is the protein affected in XLA, a disease identified as a B cell differentiation defect. Btk is crucial for B cell differentiation and activation, but its role in other cells is not fully understood. This review fo...

Myosins comprise a family of motor proteins whose role in muscle contraction and motility in a large range of eukaryotic cells has been widely studied. Although these proteins have been characterized extensively and much is known about their function in different cellular compartments, little is known about these molecules in hematopoietic cells. M...

IL-12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12Rβ1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12Rβ1 thus abolishes both IL-12 and IL-23 signaling. IL-12Rβ1 defic...

Dengue virus (DENV) RNA replication requires 2 viral proteins, non-structural protein 3 (NS3) and NS5. NS5 consists of 2 functional domains: a methyltransferase (MTase) domain involved in RNA cap formation and located in the amino terminal region and a RNA-dependent RNA polymerase domain essential for virus replication and located in the carboxyl t...

BCG vaccine contains low virulence Mycobacterium bovis bacillus. In Mexico it is given at birth with few reported adverse reactions in immunocompetent children; however, in immuno-compromised patients it can cause serious local or systemic adverse reactions. The most frequent related diseases include chronic granulomatous disease (CGD), human immun...