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1.
Microbes Infect ; 25(4): 105103, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36681177

RESUMEN

B-cell depleting therapies result in diminished humoral immunity following vaccination against COVID-19, but our understanding on the impact on cellular immune responses is limited. Here, we performed a detailed analysis of cellular immunity following mRNA vaccination in patients receiving B-cell depleting therapy using ELISpot assay and flow cytometry. Anti-SARS-CoV-2 spike receptor-binding domain antibody assays were performed to elucidate B-cell responses. To complement our cellular analysis, we performed immunophenotyping for T- and B-cell subsets. We show that SARS-CoV-2 vaccination using mRNA vaccines elicits cellular T-cell responses in patients under B-cell depleting therapy. Some facets of this immune response including TNFα production of CD4+ T-cells and granzyme B production of CD8+ T-cells, however, are distinctly diminished in these patients. Consequently, it appears that the finely coordinated process of T-cell activation with a uniform involvement of CD4+ and CD8+ T-cells as seen in HCs is disturbed in autoimmune patients. In addition, we observed that immune cell composition does impact cellular immunity as well as sustainability of anti-spike antibody titers. Our data suggest disturbed cellular immunity following mRNA vaccination in patients treated with B-cell depleting therapy. Immune cell composition may be an important determinant for vaccination efficacy.


Asunto(s)
Autoinmunidad , COVID-19 , Humanos , SARS-CoV-2 , Linfocitos T CD8-positivos , Vacunas contra la COVID-19 , Inmunidad Celular , Anticuerpos Antivirales , Vacunación
2.
Eur Neuropsychopharmacol ; 54: 90-99, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34607722

RESUMEN

Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor.


Asunto(s)
Trastorno Bipolar , COVID-19 , Vacunas , Trastorno Bipolar/epidemiología , Control de Enfermedades Transmisibles , Enfermedades Transmisibles , Humanos , Pandemias , SARS-CoV-2 , Vacunas/administración & dosificación , Vacunas/efectos adversos
3.
Front Immunol ; 12: 803742, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34950155

RESUMEN

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19+IgD+CD27- naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µL increase, 95%CI 1.02-1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.


Asunto(s)
Subgrupos de Linfocitos B/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Huésped Inmunocomprometido/inmunología , Inmunogenicidad Vacunal/inmunología , Adulto , Anciano , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Vacunas Sintéticas/inmunología , Vacunas de ARNm/inmunología
4.
Front Immunol ; 11: 576200, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33123160

RESUMEN

Schnitzler syndrome (SchS) is a rare autoinflammatory disease, characterized by urticarial rash, recurrent fever, osteo-articular pain/arthritis with bone condensation, and monoclonal gammopathy. Diagnosis may be difficult due to overlapping signs with other diseases. Here, we describe the case of a 62-year-old man with SchS, who was initially misdiagnosed with multicentric Castleman disease (MCD). As excessive release of IL-6 is characteristic of MCD, in contrast to IL-1 in SchS, we measured the phosphorylation of intracellular signaling proteins of the respective pathways by flow cytometry. We found a distinct increase of phosphorylated IRAK-4 in our patient's B cells and monocytes while phosphorylation of STAT-3 was low, suggesting predominant IL-1 signaling. In accordance with these results and the classification criteria, we established the diagnosis of SchS instead of MCD and commenced therapy with the IL-1 receptor antagonist anakinra. We observed a rapid remission of signs accompanied by a reduction of phosphorylated IRAK-4 to normal levels. In conclusion, we propose phosphorylated IRAK-4 in B cells and monocytes as a potential marker for diagnosis of SchS and for treatment response to IL-1 blockade.


Asunto(s)
Linfocitos B/enzimología , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Monocitos/enzimología , Síndrome de Schnitzler/enzimología , Antirreumáticos/uso terapéutico , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Biomarcadores/metabolismo , Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/inmunología , Enfermedad de Castleman/metabolismo , Diagnóstico Diferencial , Errores Diagnósticos , Citometría de Flujo , Humanos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Masculino , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/inmunología , Fosforilación , Valor Predictivo de las Pruebas , Factor de Transcripción STAT3/metabolismo , Síndrome de Schnitzler/diagnóstico , Síndrome de Schnitzler/tratamiento farmacológico , Síndrome de Schnitzler/inmunología , Resultado del Tratamiento
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