Inmunal (Spain)

Introduction Nuclear factor-kappa B (NF-κB) is a pivotal transcription factor involved in immune regulation, inflammation, and cell survival. Initially identified as a key regulator in B cell development and function, mutations in NFKB1 have been increasingly recognized as a cause of inborn errors of immunity (IEIs), particularly common variable immunodeficiency (CVID). NF-κB also mediates inflammatory responses across various cell types, contributing to a wide array of clinical phenotypes. Variants in NFKB1 exhibit incomplete penetrance and variable expressivity, leading to diverse immunological and autoinflammatory conditions. Objective To characterize the clinical, immunological, and genetic features of patients harboring heterozygous NFKB1 variants from four unrelated Argentine families. Methods This retrospective study analyzed clinical data, laboratory results, and genetic findings from patients seen at the Bezrodnik Immunology Centre and Hospital El Cruce. Results A total of nine patients from four unrelated families carrying heterozygous NFKB1 variants were included. All variants were classified as likely pathogenic, according to the American College of Medical Genetics and Genomics/ClinGen guidelines. Two novel variants were identified: c.202G>A (p.Gly68Ser) and c.936_937del (p.Val313Fs). Sex distribution: four females and five males, median-age 26 years (range 6–75). Clinically, 55% experienced recurrent respiratory infections, 33% had lymphoproliferative features such as adenopathy and splenomegaly, and 22% presented with autoimmune cytopenias. Other manifestations: chronic diarrhea (11%) and onychomycosis (11%). Immunologically, hypogammaglobulinemia was observed in 66%, and reduced switched memory B cells in the same proportion. One exhibited CD21low 21%. Treatment approaches: 55% received immunoglobulin replacement therapy, three patients were on immunosuppressants (mycophenolate mofetil and systemic steroids), and one with rituximab. Interestingly, two asymptomatic carriers were identified, highlighting incomplete penetrance. Conclusion Heterozygous NFKB1 variants are associated with a broad spectrum of clinical phenotypes, including antibody deficiencies, lymphoproliferation, and autoinflammatory features. Further research into the mechanisms of phenotypic variability will enhance our understanding of NF-κB pathway disorders and inform future therapeutic approaches.

This letter to the editor aims to address issues related to asthma control and quality of life in asthmatic children and their caregivers. Among the main issues is poor quality of life related to the misuse of medications and poor control of their disease. It's important to emphasize on other aspects not mentioned in the article, such as considering anxiety and depression and mental health disorders, as well as implementing educational programs to improve control and therefore improve quality of life.

Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor's plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.

Introduction: multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory disorder related to SARS-CoV-2 infection, characterized by a release of cytokines and oxidative stress, due to uncontrolled immune activation, which becomes critical in patients with a compromised antioxidant (AO), such as patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.Clinical case: we present a 3-month-old boy with G6PD deficiency who, three weeks after his mother had COVID-19, presented with fever, abdominal pain, dehydration, and shock.By epidemiological contact, positive RT-PCR was obtained for SARS-CoV-2.Laboratory tests showed elevated inflammatory markers, coagulopathy, and significant myocardial compromise.He was treated with intravenous immunoglobulin (IVIG) and systemic steroids with favorable clinical course.Conclusion: MIS-C in patients with G6PD deficiency should be identified early to establish immediate treatment and avoid serious complications both due to MIS-C and those that occur in patients with G6PD deficiency.

Introducción: La inmunodefi ciencia combinada grave se caracteriza por defecto inmunológico, debido a linfopenia de células T, con o sin defi ciencia de células B y células NK, provocando infecciones graves y de inicio temprano en la vida por agentes oportunistas como hongos, bacterias y/o virus, representando una emergencia pediátrica.Reporte de caso: Presentamos el caso de un paciente masculino que a los dos meses de edad presentó fi ebre persistente, linfopenia y ausencia de sombra tímica en la radiografía de tórax; además, se integró el diagnóstico de inmunodefi ciencia combinada grave con niveles de inmunoglobulinas bajos, tamiz metabólico neonatal ampliado con cuantifi cación de círculos de escisión del receptor de células T (TREC's) y subpoblaciones de linfocitos bajos.Se estableció tratamiento con gammaglobulina intravenosa y recibió trasplante de células progenitoras hematopoyéticas, lo cual fracasó por infección viral enteral crónica y falleció posterior a sepsis gastrointestinal con choque séptico.Conclusión: La presentación temprana y gravedad de síntomas deben hacer la sospecha para un diagnóstico y tratamiento oportuno, con un impacto directo en el pronóstico y calidad de vida.

One step, simple, robust and "green" methodology to fabricate high-density ordered arrays of uniform gold nanoparticles and gold nanoparticles clusters at room temperature over large areas which are suitable for high-performance SERS.

Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-ε, an intracellular protein with no obvious role in complement. These data support an alternative, complement-independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-ε gene in a cohort with atypical hemolytic uremic syndrome was analyzed. Eighty-three patients with early-onset atypical hemolytic uremic syndrome (<2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-ε. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. Four patients carried mutations in diacylglycerol kinase-ε, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-ε and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol kinase-ε and C3 mutations. Data suggest that complement dysregulation influences the onset and disease severity in carriers of diacylglycerol kinase-ε mutations and that treatments on the basis of plasma infusions and complement inhibition are potentially useful in patients with combined diacylglycerol kinase-ε and complement mutations. A comprehensive understanding of the genetic component predisposing to atypical hemolytic uremic syndrome is, therefore, critical to guide an effective treatment.