Bothrops atrox envenomations are common in the Brazilian Amazon. The venom of B. atrox is highly inflammatory, which results in severe local complications, including the formation of blisters. Moreover, there is little information on the immune mechanisms associated with this condition. Thus, a longitudinal study was carried out to characterize the profile of the cell populations and soluble immunological mediators in the peripheral blood and blisters in B. atrox patients s according to their clinical manifestations (mild and severe). A similar response in both B. atrox patient groups (MILD and SEV) was observed, with an increase in inflammatory monocytes, NKT, and T and B cells, as well as CCL2, CCL5, CXCL9, CXCL10, IL-1β and IL-10, when compared with the group of healthy blood donors. After the administration of antivenom, the participation of patrolling monocytes and IL-10 in the MILD group was observed. In the SEV group, the participation of B cells was observed, with high levels of CCL2 and IL-6. In the blister exudate, a hyperinflammatory profile was observed. In conclusion, we revealed the involvement of cell populations and soluble mediators in the immune response to B. atrox envenomation at the local and peripheral level, which is related to the onset and extent of the inflammation/clinical manifestation.

Inflammation is a physiological mechanism of the immune response and has an important role in maintaining the hematopoietic cell niche in the bone marrow. During this process, the participation of molecules produced by innate immunity cells in response to a variety of pathogen-associated molecular patterns and damage-associated molecular patterns is observed. However, chronic inflammation is intrinsically associated with leukemogenesis, as it induces DNA damage in hematopoietic stem cells and contributes to the creation of the preleukemic clone. Several factors influence the malignant transformation within the hematopoietic microenvironment, with inflammasomes having a crucial role in this process, in addition to acting in the regulation of hematopoiesis and its homeostasis. Inflammasomes are intracellular multimeric complexes responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β and interleukin-18 and the cell death process via pyroptosis. Therefore, dysregulation of the activation of these complexes may be a factor in triggering several diseases, including leukemias, and this has been the subject of several studies in the area. In this review, we summarized the current knowledge on the relationship between inflammation and leukemogenesis, in particular, the role of inflammasomes in different types of leukemias, and we describe the potential therapeutic targets directed at inflammasomes in the leukemic context.

The relationship between the IL1B-511C>T (rs16944) polymorphism and the risk of developing hematologic malignancies remains controversial. Thus, we performed a meta-analysis to evaluate the association between IL1B-511C>T polymorphism and the risk of developing hematologic malignancies. A comprehensive search was conducted to identify all eligible studies on IL1B-511C>T polymorphism and hematologic malignancies. Twelve case-control studies, with 2,896 cases and 3,716 controls, were selected for the analysis. The overall data failed to indicate a significant association between IL1B-511C>T polymorphism and the risk of hematologic malignancies (OR:1.06, 95% Confidence Interval [CI]: 0.93-1.22). Moreover, non-significant associations were observed in a stratified analysis according to neoplasm type (multiple myeloma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma), ethnicity (European and Asian), and Hardy-Weinberg equilibrium. In summary, our results suggest that there is no association between the IL1B-511C>T polymorphism and the risk of hematologic malignancies. As such, further large-scale studies are needed to confirm our findings.

Background: Severe COVID‐19 is marked by profound immune dysregulation, yet the interplay between humoral and inflammatory responses that determines clinical outcomes in critically ill patients remains incompletely understood. We evaluated longitudinal antibody and soluble immune mediator profiles to identify prognostic signatures associated with survival in severe COVID‐19. Methods: In this prospective longitudinal study, peripheral blood samples were collected from 30 unvaccinated adults with severe COVID‐19 admitted to the intensive care unit (ICU) and 30 healthy controls. Serum concentrations of SARS‐CoV‐2–specific IgM, IgG and IgA antibodies (S1, RBD and N) and 27 cytokines, chemokines and growth factors were quantified at ICU admission (D0), Day 7 (D7) and Day 14 (D14) using Luminex multiplex assays. Patients were classified according to clinical outcome: discharge (DIS) or death (DEA). Results: DIS and DEA patients exhibited distinct immunological trajectories. DEA patients showed early elevations of IgM anti‐N and IgM anti‐RBD at D0, accompanied by increased IFN‐γ. At D7, persistently elevated TNF‐α and FGF‐basic differentiated nonsurvivors, while by D14, higher levels of CXCL8, CCL4, CXCL10 and G‐CSF were strongly associated with mortality. In contrast, DIS patients exhibited more coordinated immune regulation, including sustained IL‐13 production and higher IgA anti‐S1 and IgA anti‐RBD levels. Conclusions: Integrated humoral and inflammatory signatures, particularly early IgM anti‐N/anti‐RBD responses and sequential increases in IFN‐γ, TNF‐α, FGF‐basic, CXCL8, CCL4, CXCL10 and G‐CSF, highlight immune signatures associated with poor outcomes. IL‐13 and coordinated antibody interactions may reflect protective immune pathways. These findings highlight the prognostic value of multidimensional immune monitoring in severe COVID‐19.

Background: Tumor suppressor genes play a central role in cancer development, and inherited genetic variation may influence both disease susceptibility and clinical outcomes. This study aimed to investigate the frequency and prognostic relevance of TP53 polymorphic variants in patients with acute lymphoblastic leukemia (ALL) from an admixed population in the Brazilian Amazon. Methods: A population-based case–control study was conducted including 193 patients diagnosed with ALL and 215 healthy controls. Germline TP53 polymorphisms rs1042522 and rs1642785 were genotyped, and allele and genotype frequencies were compared between groups. Associations with ALL susceptibility, relapse, and mortality were evaluated using multiple genetic models adjusted for age and sex. Combined genotype and haplotype analyses were performed, and overall survival was estimated using Kaplan-Meier curves and log-rank tests. Results: The CC genotype and the allele C were more frequent among ALL cases than controls. The allele C of rs1042522 ( p = 0.021) and rs1642785 ( p = 0.022) was associated with increased susceptibility to ALL. In addition, the allele C of rs1042522 was associated with a higher risk of relapse ( p = 0.016) and death ( p = 0.009). Protective effects against ALL were observed under the recessive model for rs1042522 ( p = 0.019) and the codominant model for rs1642785 ( p = 0.013). Both variants showed protective associations with mortality under the log-additive model. Combined genotype analysis revealed that the CG and GG genotypes of rs1042522 were associated with a reduced risk of relapse ( p < 0.001). Overall survival analysis showed reduced survival associated with the CC genotype, whereas improved survival was observed for the heterozygous CG genotype. Haplotype analysis indicated that the GG haplotype was associated with a reduced risk of ALL ( p = 0.007) and death ( p = 0.013). Conclusions: Our findings suggest that germline TP53 variants rs1042522 and rs1642785 modulate susceptibility and clinical outcomes in ALL, supporting their potential role as prognostic biomarkers. This study highlights the importance of population-based genomic investigations in underrepresented populations.

Human leukocyte antigen G (HLA‐G) is a nonclassical major histocompatibility complex class I molecule whose increased expression has been consistently associated with unfavorable prognosis in solid tumors and has emerged as a potential immunotherapeutic target in hematological malignancies. HLA‐G exhibits limited genetic diversity and generates multiple isoforms that play a critical role in immune tolerance, being physiologically expressed in immunoprivileged tissues and aberrantly upregulated in a variety of pathological conditions, including cancer. Accumulating evidence indicates that elevated HLA‐G expression contributes to tumor immune evasion and influences clinical outcomes in patients with leukemia, lymphoma, and multiple myeloma. Genetic variability within the HLA‐G gene, particularly polymorphisms located in regulatory regions such as the 14‐base pair insertion/deletion, has been associated with cancer susceptibility, disease progression, and adverse prognosis. In hematological malignancies, specific genotypes, including the homozygous deletion variant, have been linked to increased levels of membrane‐bound and soluble HLA‐G, correlating with impaired immune surveillance and reduced survival, particularly in chronic lymphocytic leukemia. Moreover, HLA‐G expressions may be modulated by inflammatory cytokines, such as interferon‐γ, further shaping the immunosuppressive tumor microenvironment. By functioning as a nonclassical immune checkpoint, HLA‐G represents a promising target for innovative immunotherapeutic strategies, including immune checkpoint blockade combinations and chimeric antigen receptor (CAR)‐T cell approaches directed against HLA‐G‐expressing malignant cells. In this review, we summarize current knowledge regarding HLA‐G expression, genetic polymorphisms, and immunoregulatory mechanisms in hematological malignancies, highlighting their clinical and translational implications. Improved understanding of HLA‐G‐mediated immune modulation may contribute to the development of novel prognostic biomarkers and therapeutic strategies aimed at restoring effective antitumor immunity.