Assessment of Long-Term in vitro Multiplied Human Wharton's Jelly-Derived Mesenchymal Stem Cells prior to Their Use in Clinical Administration.

The quantity of mesenchymal stem/stromal cells (MSCs) required for a particular therapy demands their subsequent expansion through ex vivo culture. During in vitro multiplication, they undergo replicative senescence which may alter their genetic stability. Therefore, this study was aimed to analyze cellular, molecular, and chromosomal alterations in Wharton's jelly-derived MSCs (WJ-MSCs) during their in vitro sequential passages, where WJ-MSCs were sequentially passaged up to P14 and cells were evaluated at an interval of P2, P6, P10, and P14.

CD8 + T Cells Exhibit an Exhausted Phenotype in Hemophagocytic Lymphohistiocytosis.

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome mainly caused by uncontrolled activation of antigen presenting cells and CD8 T cells. CD8 T cell exhaustion is a known phenomenon in chronic viral infections and cancer. However, the role of T cell exhaustion is not yet identified in HLH in the background of persistent inflammation.

Rare hereditary nonspherocytic hemolytic anemia caused by a novel homozygous mutation, c.301C > A, (Q101K), in the AK1 gene in an Indian family.

Background: Adenylate kinase (AK) deficiency is a rare red cell enzymopathy associated with moderate to severe congenital nonspherocytic hemolytic anemia, along with mental and psychomotor retardation (in exceptional cases). Only ten mutations have been detected in the AK1 gene to date. In this study, we aimed to diagnose the unexplained issue of haemolytic anaemia and offer antenatal screening to the family.

Whole genome sequencing identifies novel structural variant in a large Indian family affected with X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA, OMIM #300755) is a primary immunodeficiency disorder caused by pathogenic variations in the BTK gene, characterized by failure of development and maturation of B lymphocytes. The estimated prevalence worldwide is 1 in 190,000 male births. Recently, genome sequencing has been widely used in difficult to diagnose and familial cases.

A case of disseminated subcutaneous phaeohyphomycosis caused by Exserohilum rostratum with CARD9 mutation.

Phaeohypomycosis is a rare cutaneous and subcutaneous fungal infection caused by dematiaceous fungi. They have a widespread global distribution occasionally affecting humans. A 26-year-old woman presented with multiple skin lesions over her face and extremities for last 7 years, unresponsive to systemic amphotericin B and itraconazole.

Approach to genetic diagnosis of inborn errors of immunity through next-generation sequencing.

Patients with inborn errors of immunity (IEI) present with a heterogeneous clinical and immunological phenotype, therefore a correct molecular diagnosis is crucial for the classification and subsequent therapeutic management. On the other hand, IEI are a group of rare congenital diseases with highly diverse features and, in most cases, an as yet unknown genetic etiology. Next generation sequencing has facilitated genetic examinations of rare inherited disorders during the recent years, thus allowing a suitable molecular diagnosis in the IEI patients.

Molecular characterization of RhD variant phenotypes among blood donors: A study from the coastal region of India.

Background: RhD expression varies with population and ethnicity. Accurate typing of RhD antigen among blood donors is important to prevent development of anti-D among recipients of blood transfusion. We aimed to screen blood donors for variant D phenotypes and accurately characterize them by genotyping.

Algorithm development and diagnostic accuracy testing for non-invasive foetal RHD genotyping: an Indian experience.

Background: The discovery of the cell-free foetal DNA (cffDNA) circulating in the maternal plasma enabled prediction of foetal RHD thus eliminating the risks associated with invasive procedures. Non-invasive foetal RHD genotyping has now become the standard approach in developed countries for management of alloimmunised women and is also used for targeted antenatal prophylaxis in non-alloimmunised women.

Materials And Methods: cffDNA was extracted from the plasma of 217 RhD negative pregnant women at a gestational age of 10-34 weeks.

The clinical efficacy of Rituximab administration in autoimmunity disorders, primary immunodeficiency diseases and malignancies.

Rituximab (RTX), as a monoclonal antibody-based immunotherapeutic intervention targeting CD20 on B cells, has proven efficacy in the treatment of patients with some immune-mediated diseases. In the present review, we provided information on the immunobiological mechanisms of signaling for RTX and its clinical applications, according to the immune-pathophysiology involved in the microenvironment of multiple diseases. We highlighted combination therapy, dose schedules, and laboratory monitoring, as well as the associated common and rare side effects to avoid.

Innovative Betulin Nanosuspension exhibits enhanced anticancer activity in a Triple Negative Breast Cancer Cell line and Zebrafish angiogenesis model.

We present a nanosuspension of betulin, a BCS class II anticancer drug, particularly effective against resistant breast cancer. As anticancer efficacy of betulin is hampered by poor aqueous solubility, a nanosuspension with surface area was considered to enhance efficacy. An innovative approach wherein the betulin nanosuspension is generated instantaneously in situ, by adding a betulin preconcentrate (BeTPC) comprising drug and excipients, to aqueous medium, is successfully demonstrated.

Clinical Profile of Hyper-IgE Syndrome in India.

Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility to skin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES.

Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India.

Background: Chronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment.

Divergence in phenotyping and genotyping analysis of the Lewis histo-blood group system.

Objectives: This study evaluated the red blood cell (RBC) Lewis phenotypes by simple haemagglutination technique and molecular genotyping in healthy individuals.

Background: The expression of Lewis antigen on RBCs is dependent on the interaction of FUT3 and FUT2 genes. Complexity of the genetic control of Lewis antigen expression and the error-prone nature of Lewis phenotyping result in non-genuine RBC Lewis phenotypes, which could be misleading.

Erythrocytes as a preferential target of oxidative stress in blood.

Red blood cells (RBC) are specifically differentiated to transport oxygen and carbon dioxide in the blood and they lack most organelles, including mitochondria. The autoxidation of hemoglobin constitutes a major source of reactive oxygen species (ROS). Nitric oxide, which is produced by endothelial nitric oxide synthase (NOS3) or via the hemoglobin-mediated conversion of nitrite, interacts with ROS and results in the production of reactive nitrogen oxide species.

Prenatal Diagnosis for Primary Immunodeficiency Disorders-An Overview of the Indian Scenario.

Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease. This paper discusses the prenatal services available for affected families at various centers across the country and the challenges and ethical considerations associated with genetic counseling.

Molecular characterization of rare D--/D-- variants in individuals of Indian origin.

Background: Rh antigens are critical in haemolytic disease of the foetus and newborn (HDFN). The D-- phenotype is a rare blood group characterised by the lack of expression of C, c, E and e antigens at the surface of red blood cells because of mutations in both RHCE alleles inactivating the expression of a "normal" protein. The aim of the study was to determine the molecular basis of D-- individuals of Indian origin.

Significance of heme oxygenase-1(HMOX1) gene on fetal hemoglobin induction in sickle cell anemia patients.

Though the patients with sickle cell anemia (SCA) inherit same genetic mutation, they show considerable phenotypic heterogeneity. It has been observed that patients with elevated fetal hemoglobin (HbF) levels have a relatively mild clinical course. There is sparse literature on the association of higher HbF levels leading to reduction in the oxidative stress in SCA patients.

Red cell antigen phenotypes in blood donors & thalassaemia patients for creation of red cell antigen-matched inventory.

Background & Objectives: Patients with thalasssaemia are at a risk of alloimmunization and the presence of RBC alloantibodies further complicates transfusion therapy. Matching for the critical antigens of Rh, Kell, Kidd and Duffy blood group systems has been shown to minimize alloimmunization. The aim of the present study was to create a database of extensively typed donors for clinically significant and common blood group antigens of Rh, Kidd, Kell and Duffy systems for transfusion therapy of multitransfused thalassaemic patients.

Prevalence and spectrum of mutations causing G6PD deficiency in Indian populations.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human erythroenzymopathy affecting around 10% of the world population. India is endemic for malaria and antimalarial drugs are known to induce haemolysis in G6PD deficient individuals. Here we report the prevalence as well as the molecular diversity of G6PD deficiency in geographical regions of India.

Chalazia, A Late Manifestation of Primary Immunodeficiency Disorders.

To call attention to the central clues for primary immunodeficiency in the cases reported by María Nieves-Moreno et. al where chalazia in the reported cases is undoubtedly an important clue but is a late clinical manifestation.

Impaired NK cell activation during acute dengue virus infection: A contributing factor to disease severity.

Dengue viral (DENV) infection has a broad clinical spectrum ranging from classical febrile illness to life-threatening disease. Literature suggests that spectrum of illness could be due to differences in innate immune-responses; however, the knowledge is still at infancy. Amongst the various cells involved in innate immune responses, NK cells play a central role, particularly in anti-viral immunity.

2019 Update on Primary Immunodeficiency Disorders by the International Union of Immunological Societies.

International Union of Immunological Societies working group recently updated the human inborn errors of immunity. This classification includes 65 new disorders that have been added since the last classification in 2018. This article highlights the important aspects of new classification for the benefit of general pediatricians.