Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma: New hopes on the horizon.

In this editorial, we comment on the article by Wang et al. This manuscript explores the potential synergistic effects of combining zanubrutinib, a novel oral inhibitor of Bruton's tyrosine kinase, with high-dose methotrexate (HD-MTX) as a therapeutic intervention for primary central nervous system lymphoma (PCNSL). The study involves a retrospective analysis of 19 PCNSL patients, highlighting clinicopathological characteristics, treatment outcomes, and genomic biomarkers. The results indicate the combination's good tolerance and strong antitumor activity, with an 84.2% overall response rate. The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL, particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B. Furthermore, the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring. In essence, the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL. The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes. While the findings suggest promise, the study's limitations should be considered, and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Enhancing innate immunity against virus in times of COVID-19: Trying to untangle facts from fictions.

INTRODUCTION: In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. METHODS: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). RESULTS: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. CONCLUSION: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.

Basophils and allergic inflammation.

Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in human subjects and murine systems have shown that basophils perform nonredundant effector functions and significantly contribute to the development and progression of TH2 cytokine-mediated inflammation. Although the potential functions of murine and human basophils have provoked some controversy, recent genetic approaches indicate that basophils can migrate into lymphoid tissues and, in some circumstances, cooperate with other immune cells to promote optimal TH2 cytokine responses in vivo. This article provides a brief historical perspective on basophil-related research and discusses recent studies that have identified previously unappreciated molecules and pathways that regulate basophil development, activation, and function in the context of allergic inflammation. Furthermore, we highlight the unique effector functions of basophils and discuss their contributions to the development and pathogenesis of allergic inflammation in human disease. Finally, we discuss the therapeutic potential of targeting basophils in preventing or alleviating the development and progression of allergic inflammation.

Dinamica de resuuesta inmune primaria y secundaria: modelo: anticuerpos anti hbs / Dynamics of the immune primary and secondary response: Model, antibodies HBS

Se estudió la cinética individual y colectiva de la dinámica de la respuesta inmune y sus categorías, utilizando como modelo la respuesta de anticuerpos contra el antígeno de superficie del virus productor de la hepatitis B. En estudiantes de Medicina latinoamericanos, de 20 años promedio, se cuantificó la permanencia de niveles de anticuerpos después de 3 años de un esquema completo de inmunización y se encontraron valores promedio de 168 UI/L, un incremento de 757 UI/L en 15 días post refuerzo, lo que permitió estudiar el índice de memoria / durabilidad que fue 5,5 y conocer el incremento en UI/L por día y por microgramo de antígeno: 29 UI/ µg de antígeno. Se estimó, a partir de los valores de durabilidad a los 3 años de vacunados, la intensidad de la respuesta post esquema, que fue 336UI/L; igualmente a partir de los valores alcanzados al analizar memoria, 925 UI/L, pronosticamos una seroprotección hasta 18 años más, es decir, hasta el 2023. Obtuvimos resultados preliminares de utilización del modelo cinético para estudio de inmunoeficiencia.

It was studied the individual and collective kinetics of the dynamics of the immune response and their categories using like a model the response of antibodies against the antigen of surface of the virus producing of the hepatitis B. In students of Medicine 20 years old average, a permanency of antibodies of 168 UI/L was observed, after 3 years of a complete outline of immunization, an increment of 757 UI/L in 14 days post booster, what allowed to study the index by memory / durability that was 5.5 and to know the increment in UI/L per day (54 UI/day) and for antigen micro-gramme: 37.8 UI/µg. It was considered, starting from permanency of antibodies to the 3 years of vaccination, the intensity of the response post schedule that was 336UI/L, equally starting from the values reached in the memory, 925 UI/L, we prognosis a seroprotection up to 18 years or more, that is to say up to the 2023. We obtained preliminary results of use of the kinetic pattern for immune-efficiency study.