Omicron Breakthrough Infection After Heterologous Prime-Boost Vaccination Induces a Vigorous Antibody Response.

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is usually asymptomatic or mild and appears to be poorly immunogenic at least in unvaccinated individuals. Here, we found that health care workers vaccinated with 2 doses of Sputnik V and a booster dose of ChAdOx1 mount a vigorous neutralizing-antibody response after Omicron breakthrough infection.

A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation.

BACKGROUND: A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection. OBJECTIVE: To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy. DESIGN: Detailed investigation of virologic and immunologic characteristics. SETTING: Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts. PATIENT: A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication. MEASUREMENTS: Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing. RESULTS: No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4+ T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. LIMITATIONS: Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved. CONCLUSION: Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection. PRIMARY FUNDING SOURCE: National Institutes of Health and Bill & Melinda Gates Foundation.

[Iron intake and HFE gen in male adults from Buenos Aires]. / Ingesta de hierro y gen HFE en varones adultos de Buenos Aires.

Excess iron (Fe) intake in subjects carrying certain mutations in the HFE gene may result in Fe overload. To estimate risk of Fe overload, 166 male blood donors (19-65 years) from Buenos Aires city were investigated. Daily Fe intake (FeI), hem Fe intake, and Fe intake from SO4Fe enriched flours were estimated (SARA Computer Program and Food Composition Table, USDA). Serum ferritin and transferrin saturation were determined; criteria for Fe overload was serum ferritin > 300 ng/ml and transferrin saturation = 50%. HFE genotypes C282Y, H63D and S65C were analyzed by PCR-RFLP in blood samples. No participant presented FeI lower than the estimated average requirement (6 mg Fe/day) and 3.0% was over the upper level (45 mg Fe/day). Hem Fe and Fe from flour enrichment were 9.4% and 47.7% of daily Fe intake, respectively. A significant association was observed between the increase in serum ferritin (ng/ml) and the increase in FeI (p = 0.0472); 2.3% of the donors presented serum ferritin > 300 ng/ml and transferrin saturation = 50%. Genotypes associated with hereditary hemochromatosis (H63D, S65C and C282Y) were found in 29.3% of the donors. The percentage of transferrin saturation was higher in subjects carrying mutation than in wild type subjects (p = 0.0167). Although penetrance of hereditary hemochromatosis in the studied group was only 1.2%, an excessive Fe intake could enhance adverse effects in individuals unaware of any family history of Fe overload.

Ingesta de hierro y gen HFE en varones adultos de Buenos Aires / Iron intake and HFE gen in male adults from Buenos Aires

El consumo excesivo de hierro (Fe) en portadores de mutaciones en el gen HFE puede resultar en sobrecarga. Para evaluar el riesgo de sobrecarga de Fe fueron investigados 166 varones adultos donantes de sangre de la ciudad de Buenos Aires. Se estimó la ingesta diaria de Fe (IFe), de Fe hemínico y de Fe proveniente de harinas enriquecidas con SO4Fe. Se determinó ferritina sérica y porcentaje de saturación de transferrina (criterio de sobrecarga de Fe: ferritina sérica > 300 ng/ml y saturación de transferrina ≥ 50%). Las mutaciones C282Y, H63D y S65C fueron investigadas en sangre mediante PCR-RFLP. Todos los participantes cubrieron ampliamente el requerimiento estimado promedio de Fe (6 mg Fe/día) y 3.0% superó el máximo tolerable (45 mg Fe/día). El Fe hemínico correspondió al 9.4% de la IFe y el de harinas enriquecidas al 47.7%. Se observó una asociación entre el aumento de IFe y el de ferritina sérica (p = 0.0472), y el 2.3% de los donantes presentaron ferritina sérica > 300 ng/ml y saturación de transferrina ≥ 50%. El 29.3% de los donantes eran portadores de los genotipos H63D, S65C o C282Y, asociados a hemocromatosis hereditaria, y tenían valores de saturación de transferrina significativamente mayores a los de los donantes wild type (p = 0.0167). Si bien la incidencia clínica de hemocromatosis hereditaria fue baja en el grupo estudiado (1.2%), el consumo excesivo de Fe plantea un riesgo potencial para la salud de individuos que ignoran sus antecedentes familiares de sobrecarga de Fe.

Excess iron (Fe) intake in subjects carrying certain mutations in the HFE gene may result in Fe overload. To estimate risk of Fe overload, 166 male blood donors (19-65 years) from Buenos Aires city were investigated. Daily Fe intake (FeI), hem Fe intake, and Fe intake from SO4Fe enriched flours were estimated (SARA Computer Program and Food Composition Table, USDA). Serum ferritin and transferrin saturation were determined; criteria for Fe overload was serum ferritin > 300 ng/ml and transferrin saturation ≥ 50%. HFE genotypes C282Y, H63D and S65C were analyzed by PCR-RFLP in blood samples. No participant presented FeI lower than the estimated average requirement (6 mg Fe/day) and 3.0% was over the upper level (45 mg Fe/day). Hem Fe and Fe from flour enrichment were 9.4% and 47.7% of daily Fe intake, respectively. A significant association was observed between the increase in serum ferritin (ng/ml) and the increase in FeI (p = 0.0472); 2.3% of the donors presented serum ferritin > 300 ng/ml and transferrin saturation ≥ 50%. Genotypes associated with hereditary hemochromatosis (H63D, S65C and C282Y) were found in 29.3% of the donors. The percentage of transferrin saturation was higher in subjects carrying mutation than in wild type subjects (p = 0.0167). Although penetrance of hereditary hemochromatosis in the studied group was only 1.2%, an excessive Fe intake could enhance adverse effects in individuals unaware of any family history of Fe overload.

Crioglobulina con propiedad crioaglutinina en un paciente con linfoma esplénico de zona marginal / Cryoglobulin with cold agglutinin properties in a patient with splenic marginal zone lymphoma / Crioglobulina com propriedade crioaglutinina em um paciente com linfoma esplênico de zona marginal

El objetivo del trabajo fue describir un caso de linfoma esplénico de zona marginal (LEZM) con un componente monoclonal que posee propiedades de crioglobulina y crioaglutinina, un hallazgo de muy baja frecuencia. Una paciente con LEZM padeció una anemia hemolítica autoinmune 5 años después del diagnóstico, con hematocrito de 0,15 L/L, hemoglobina 49 g/L, lactato deshidrogenasa 16,82 μkat/L, prueba de Coombs directa positiva con anti- IgG/C3d, bilirrubina total 90,6 μmol/L e indirecta de 58,1 μmol/L. No presentó evidencia clínica ni serológica de infección por VIH, hepatitis B ni C. El proteinograma sérico presentó un pico monoclonal de 14 g/L, con crioglobulinemia positiva a las 24 h, y un criocrito de 30%. La crioglobulina purificada fue de tipo I con un componente monoclonal IgM-lambda, coincidente al observado en suero. El suero, el eluato a 37 °C y la crioglobulina purificada de la paciente presentaron actividad de crioaglutinina con especificidad anti-I, fenómeno producido por la misma inmunoglobulina. El hallazgo de una crioglobulina con propiedades de crioaglutinina en pacientes con LEZM no ha sido descrito previamente en la bibliografía.

The aim of this paper is to describe a case of splenic marginal zone lymphoma (SMZL) with monoclonal component having properties of cryoglobulin and cold agglutinin, a finding of very low frequency. A patient with SMZL suffered autoimmune hemolytic anemia five years after diagnosis, with hematocrit 0.15 L/L, hemoglobin 49 g/L, lactate dehydrogenase 16.82 μkat/L, direct Coombs test with anti-IgG/C3d positive, total bilirubin 90.6 μmol/L and indirect 58.1 μmol/L. She presented no clinical or serological evidence of HIV, hepatitis B or C infection. Serum protein electrophoresis showed a monoclonal peak of 14 g/L, with positive cryoglobulinemia at 24 hours, and 30% cryocrit. Purified cryoglobulin was type I with a monoclonal IgM-lambda component coincident with that observed in serum. The patient serum, eluate at 37 °C and purified cryoglobulin showed cold agglutinin activity with anti-I specificity, phenomenon produced by the same immunoglobulin. The finding of a cryoglobulin with cold agglutinin properties in patients with SMZL has not been previously described in the literature.

O objetivo do trabalho foi descrever um caso de linfoma esplênico de zona marginal (LEZM) com um componente monoclonal com propriedades do crioglobulina e crioaglutinina, um achado de muito baixa frequência. Um doente com LEZM sofreu uma anemia hemolítica autoimune cinco anos após o diagnóstico, com hematócrito de 0,15 L/L, hemoglobina 49 g/L, lactato desidrogenase de 16,82 μkat/L, teste de Coombs direto positivo com anti-IgG/C3d, bilirrubina total 90,6 μmol/L e indireta 58,1 μmol/L. Não apresentou evidência clínica ou sorológica de infecção por HIV, hepatite B ou C. O proteinograma sérico mostrou um pico monoclonal de 14 g/L, com crioglobulinemia positiva 24 horas, e um criocrito de 30%. Crioglobulina purificada foi tipo I com o componente monoclonal IgM-lambda, coincidente com a observada no soro. O soro, o eluato a 37 ° C e a crioglobulina purificada do paciente mostraram atividade de crioaglutinina com especificidade anti-I, fenômeno produzido pela mesma imunoglobulina. O achado de uma crioglobulina com propriedades de crioaglutinina em pacientes com LEZM não foi previamente descrito na literatura.