Specific Cellular and Humoral Immune Responses to the Neoantigen RBD of SARS-CoV-2 in Patients with Primary and Secondary Immunodeficiency and Healthy Donors.

Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.

Early Prediction of Subsequent Molecular Response to Nilotinib in Patients with Chronic Myeloid Leukemia: Comparison of the Quantification of BCR-ABL1 Ratios Using ABL1 or GUSB Control Genes.

Molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). Quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to frontline nilotinib was studied using data from 60 patients with chronic-phase CML from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) substudy. Effects of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early time points as independent variables on subsequent MR were determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses. From day 45, concordance was found for both control genes' early transcript kinetics and ability to predict subsequent deep MR at 18 months. From baseline to 3 months, transcripts descended linearly with both control genes. Use of ABL1 allowed for an earlier prediction (2 months) of subsequent MR than with GUSB (3 months), with cut-off values of 1.5% and 0.19%, respectively. The dynamic determination of BCR-ABL1 transcripts using either internal control gene is valid and predictive of subsequent MR. The use of GUSB to predict an earlier and more accurate response than ABL1 is not supported in the results. Accurate early indicators of MR are essential to identify patients likely to have inferior outcomes who may benefit from treatment with an alternative tyrosine kinase inhibitor.

[Association of hemoglobinopathy and alpha thalassemia. Study of 45 patients]. / Asociación de hemoglobinopatía S y alfatalasemia. Análisis de 45 casos.

BACKGROUND AND OBJECTIVE: Hemoglobin S (HbS) alpha-thalassemia together with ss-thalassemia and hemoglobins C, E and D are named common hemoglobinopathies. In this study, we analyzed the frequency of the association between alpha-thalassemia and HbS and its phenotypic expression. PATIENTS AND METHOD: Since January 1995 to March 2003 we studied 83 cases of HbS, which were diagnosed by electrophoretic and chromatographic criteria. The molecular study was carried out by Southern blot with the restriction enzymes Bam HI and Bgl II and a (1.5 Kb Pst) and z (1.8 Kb Sac Y) probes. RESULTS: 45 cases (54.2%) had a-thalassemia (36 -alpha3,7/aa; 1-alpha4,2/alphaalpha; 6 -alpha3,7/-alpha3,7; 1-alpha4,2/-alpha4,2); 36 had not alpha-thalassemia and in two cases there were a triplication of a genes. The patients with HbS heterozygote associated with alpha-thalassemia showed a percentage of HbS (p < 0.0001), CMV (p = 0.004), MCH (p = 0.002) and MCHC (p = 0.02) significantly lower than the cases of HbS without this association. However, no differences between both groups were found with regard to the rest of parameters analyzed (Hb p = 0.56; PVC p = 0.84; RDW p = 0.06; Reticulocytes p = 0.26; HbF p = 0.76; HbA2 p = 0.13). In the cases with a severe form of disease (HbS homozygote; HbS/Hb C; HbS/beta-thalassemia), patients with alpha-thalassemia had a number of leukocytes that was significantly lower than that of patients without alpha-thalassemia (p = 0.034). CONCLUSION: An association between HbS and alpha-thalassemia was common (> 50%). Screening for this association is of great interest because the clinical expression in the cases of HbS homozigote will be modulated. This association must be suspected in cases of homozygous HbS in which levels of HbS are lower than expected.

Asociación de hemoglobinopatía S y alfatalasemia. Análisis de 45 casos / Association of hemoglobinopathy and alpha thalassemia. Study of 45 patients

FUNDAMENTO Y OBJETIVO: La hemoglobina (Hb) S y la alfatalasemia son, junto con la betatalasemiay las Hb C, E y D, las denominadas hemoglobinopatías comunes, las cuales presentan una alta prevalencia en las zonas históricamente endémicas de paludismo. En este estudio analizamos la frecuencia de la asociación de estas 2 hemoglobinopatías, así como su expresión fenotípica. PACIENTES Y MÉTODO: Entre enero de 1995 y marzo de 2003 hemos realizado un estudio molecular para descartar la presencia de una alfatalasemia asociada de un total de 83 casos diagnosticados de hemoglobinopatías S por criterios electroforéticos y cromatográficos. El estudio molecular se realizó por Southern blot con las endonucleasas de restricción Bam HI y Bgl II, y lassondas α (1,5 Kb Pst I) y ζ (1,8 Kb Sac Y).RESULTADOS: De los 83 casos estudiados, 45 (54,2%) presentaban alfatalasemia (37 -α3,7/αα; 1-α4,2/αα; 6 -α3,7/-α3,7; 1 -α4,2/-α4,2); 36 no tenían alfatalasemia y en 2 había una triplicación degenes α. Los pacientes con HbS heterocigota asociada a alfatalasemia presentaron el porcentajede HbS (p 50%en nuestra experiencia). El cribado de esta asociación es de gran interés, ya que puede modularla expresión clínica de los casos de HbS homocigota. Dicha asociación se debe sospecharen los casos de HbS heterocigota con valores más bajos de HbS de lo esperado

BACKGROUND AND OBJECTIVE: Hemoglobin S (HbS) α-thalassemia together with β-thalassemia and hemoglobins C, E and D are named common hemoglobinopathies. In this study, we analyzed the frequency of the association between α-thalassemia and HbS and its phenotypic expression. PATIENTS AND METHOD: Since January 1995 to March 2003 we studied 83 cases of HbS, which were diagnosed by electrophoretic and chromatographic criteria. The molecular study was carried out by Southern blot with the restriction enzymes Bam HI and Bgl II and a (1.5 Kb Pst)and z (1.8 Kb Sac Y) probes. RESULTS: 45 cases (54.2%) had a-thalassemia (36 -α3,7/aa; 1-α4,2/αα; 6 -α3,7/-α3,7; 1-α4,2/-α4,2); 36 had not α-thalassemia and in two cases there were a triplication of a genes. The patients with HbS heterozygote associated with α-thalassemia showed a percentage of HbS(p 50%). Screening for this association is of great interest because the clinical expression in the cases of HbS homozygote will be modulated. This association must be suspected in cases of homozygous HbSin which levels of HbS are lower than expected