Lymphocyte subsets early predict mortality in a large series of hospitalized COVID-19 patients in Spain.

The role of lymphocytes and their main subsets as prognostic factors of death in SARS-CoV-2-infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)-confirmed consecutive patients by lysed-no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3-month follow-up. The 112 patients who died were older and had significantly higher frequencies of known co-morbidities than survivor COVID-19 patients. A significant reduction in total lymphocytes, CD3+ , CD4+ , CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P < 0·001), while the percentage of CD56+ /CD16+ natural killer (NK) cells was significantly higher (P < 0·001). Multivariate logistic regression analysis showed a significantly increased risk of in-hospital death associated to age [odds ratio (OR) = 2·36, 95% confidence interval (CI) = 1·9-3·0 P < 0·001]; CD4+  T counts ≤ 500 cells/µl, (OR = 2·79, 95% CI = 1·1-6·7, P = 0·021); CD8+  T counts ≤ 100 cells/µl, (OR = 1·98, 95% CI = 1·2-3·3) P = 0·009) and CD56+ /CD16+ NK ≥ 30%, (OR = 1·97, 95% CI = 1·1-3·1, P = 0·002) at admission, independent of total lymphocyte numbers and co-morbidities, with area under the curve 0·85 (95% CI = 0·81-0·88). Reduced counts of CD4+ and CD8+ T cells with proportional expansion of NK lymphocytes at admission were prognostic factors of death in this Spanish series. In COVID-19 patients with normal levels of lymphocytes or mild lymphopenia, imbalanced lymphocyte subpopulations were early markers of in-hospital mortality.

Acquired angioedema with anti-C1-inhibitor autoantibodies during assisted reproduction techniques

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Sequential combined therapy with omalizumab and rituximab: a new approach to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disease, and a significant percentage of AD patients have severe forms. Inflammation based on type 2 helper T cells (T(H)2), autoantibodies, and CD8+ T cells could play a relevant role in this disease. When the patient requires systemic immunosuppressors for disease control, side effects are frequent. We propose a sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti-immunoglobulin [Ig] E) and rituximab (anti-CD20), which might induce clinical benefit with few side effects in selected individuals with AD. METHODS: We report 6 cases of severe AD refractory to conventional therapy. The patients underwent sequential switch therapy with omalizumab and rituximab. Clinical response was assessed by means of the decrease in body surface affected. Immunological parameters and side effects were also monitored. RESULTS: Four patients received omalizumab before a high-dose cycle of rituximab. In the case of recurrences, either low-dose cycles of rituximab or omalizumab were administered. A long-term clinical benefit was observed in 3 out of 4 patients. Two patients first received high-dose rituximab followed by either low-dose rituximab or omalizumab, and one of them achieved a response at 17 months. No severe side effects were recorded. Serum IgE level and B-cell counts decreased with therapy, the latter returning to baseline levels 10 to 11 months after treatment. Specific antibody responses remained protective during the study. CONCLUSIONS: With our proposed switch therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel strategy targets different arms of the immune response and might be a good alternative for patients with severe AD.

Sequential Combined Therapy With Omalizumab and Rituximab: A New Approach to Severe Atopic Dermatitis

Antecedentes: La dermatitis atópica (DA) es una enfermedad crónica de la piel. En un porcentaje elevado de pacientes con formas graves de DA, es probable que existan autoanticuerpos y linfocitos T CD8+ actuando junto con células Th2 en la fisiopatología. En los pacientes que requieren inmunosupresores sistémicos para controlar la enfermedad, los efectos adversos son frecuentes. En este trabajo proponemos la administración secuencial de dos terapias con anticuerpos monoclonales (omalizumab, anti-IgE y rituximab, anti-CD20) como estrategia terapéutica eficaz con un grado aceptable de efectos adversos. Métodos: Presentamos 6 pacientes con DA grave y recalcitrante a inmunosupresores convencionales que recibieron terapia secuencial con omalizumab (Xolair®)/Rituximab (MabThera®). La respuesta clínica se evaluó mediante la variación en la superficie corporal afectada. Se monitorizaron parámetros inmunológicos y efectos adversos. Resultados: Cuatro pacientes recibieron omalizumab seguido de un ciclo de alta dosis de rituximab (HR). En las siguientes recaídas se administró un ciclo de baja dosis de rituximab (LR) u omalizumab. Tres de los 4 pacientes consiguieron mejoría clínica prolongada. En 2 pacientes se administró primero HR seguido o bien por LR, o por omalizumab. Uno de ellos consiguió remisión durante 17 meses. No se registraron efectos adversos graves. La IgE y las células B séricas disminuyeron tras la terapia; estas últimas no recuperaron su nivel basal hasta 10-11 meses después. Las respuestas específicas de anticuerpos permanecieron en niveles protectores durante el estudio. Conclusiones: Con esta terapia, 4 de los 6 pacientes con DA grave consiguieron una mejoría significativa. Esta estrategia se dirige específicamente a varios mecanismos efectores del sistema inmunológico y podría ser una alternativa para un grupo seleccionado de pacientes con DA grave (AU)

Background: Atopic dermatitis (AD) is a common chronic skin disease, and a significant percentage of AD patients have severe forms. Inflammation based on type 2 helper T cells (TH2), autoantibodies, and CD8+ T cells could play a relevant role in this disease. When the patient requires systemic immunosuppressors for disease control, side effects are frequent. We propose a sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti-immunoglobulin [Ig] E) and rituximab (anti-CD20), which might induce clinical benefit with few side effects in selected individuals with AD. Methods: We report 6 cases of severe AD refractory to conventional therapy. The patients underwent sequential switch therapy with omalizumab and rituximab. Clinical response was assessed by means of the decrease in body surface affected. Immunological parameters and side effects were also monitored. Results: Four patients received omalizumab before a high-dose cycle of rituximab. In the case of recurrences, either low-dose cycles of rituximab or omalizumab were administered. A long-term clinical benefit was observed in 3 out of 4 patients. Two patients first received high-dose rituximab followed by either low-dose rituximab or omalizumab, and one of them achieved a response at 17 months. No severe side effects were recorded. Serum IgE level and B-cell counts decreased with therapy, the latter returning to baseline levels 10 to 11 months after treatment. Specific antibody responses remained protective during the study. Conclusions: With our proposed switch therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel strategy targets different arms of the immune response and might be a good alternative for patients with severe AD (AU)

La importancia clínica de los polimosfirmos del gen CD45 / The clinical importance of the polymorphisms of CD45 gene

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[Cutaneous erythematous rash as first manifestation of T-cell prolymphocytic lymphatic leukemia]. / Erupción cutánea eritematosa como primera manifestación de leucemia linfática prolinfocítica de células T.

We present a case of a man 84 years-old, whose presentation feature was a cutaneous inespecific rash, and was diagnosed of T prolymphocytic leukaemia (T-PLL). In this review we analyze actual aspects concerning biology, diagnosis, classification, prognosis and treatment of this rare mature T cell leukaemia.

Erupción cutánea eritematosa como primera manifestación de leucemia linfática prolinfocítica de células T / Cutaneous involvement as the first manifestation of T-cell prolymphocytic leukaemia

Se presenta el caso de un varón de 84 años que debutó con una erupción eritematosa y en el cual se efectuó el diagnóstico de leucemia prolinfocítica T. Con este motivo, se revisan diversos aspectos actuales concernientes a la biología, diagnóstico, clasificación pronóstico y tratamiento de las leucemias de células T maduras. (AU)