IntroductionCommon variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults. 1 Recurrent bacterial infections of the respiratory tract are the clinical hallmark present in nearly all patients. 2 In addition, up to 40% of the patients show gastrointestinal disease, concomitant lymphoproliferative disorders, autoimmune phenomena, or granulomatous inflammation. 2 The pathogenic understanding of antibody deficiency in humans has always been hampered by the great heterogeneity of the syndrome. 3 In 1966, Rosen and Janeway started to group antibody deficiencies by their mode of inheritance. 4 In 1973, Cooper included the clinical course and serum immunoglobulin levels, thereby separating hyper-IgM syndromes and selective IgA deficiency. 5 The remaining group of still very heterogeneous antibody deficiencies was termed CVID. Consecutive attempts to subclassify CVID by B-cell function in vitro 6,7 failed to reach diagnostic acceptance because of laborious and poorly standardized procedures and a lack of clinical relevance.In 2002, we and others suggested a flow cytometric classification of CVID according to the B-cell phenotype. 8,9 The abnormalities of circulating B cells in patients with CVID had already been recognized earlier, 10 but only with the ease and the broad availability of flow cytometry was a widespread and systematic analysis of these aberrations possible. The Freiburg classification divided patients into 3 groups by analyzing the expression of IgM, IgD, CD27 and CD21. 8 Group 1 was characterized by a severe reduction of switched memory B cells (IgD Ϫ IgM Ϫ CD27 ϩ less than 0.4% of lymphocytes), while group 2 representing 25% of the analyzed CVID patients exhibited nearly normal numbers of class-switched memory B cells, suggesting a post germinal center defect. The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Methods PatientsAll patients were diagnosed as having CVID based on the European Society for Immunodeficiencies/Pan-American Group for Immunodeficiency (ESID/PAGID) criteria, 11 including a marked decrease of IgG (at least 2 standard deviations [SDs] below the mean for age) and a marked decrease in at least one of the isotypes IgM or IgA, the onset of clinical significant immunodeficiency at greater than 2 years of age, and the exclusion of defined causes of hypogammaglobulinemia (see also www.esid.org). Not all patients have been evaluated for absent isohemagglutinins and/or poor response to vaccines. For the final evaluation of B-cell phenotyping, the following exclusion criteria were adopted: patients younger than 6 years of age at the time of flowcytometric evaluation, patients on immunosuppressive treatment, patients suffering currently from malignancies, and patients with less than 1% peripheral B cells. Altogether, 303 patients of origi...

We describe 3 siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency, a known genetic etiology of clinical disease caused by infection with poorly virulent mycobacteria, such as mycobacteria found in bacille Calmette-Guérin (BCG) vaccines and environmental nontuberculous mycobacteria (NTM). One child had disseminated tuberculosis, the second had extraintestinal salmonellosis and pulmonary tuberculosis, and the third remained asymptomatic. IL-12Rbeta1 deficiency should be considered as a diagnosis in patients with severe salmonellosis or tuberculosis, even if they do not have disease due to BCG or NTM.

Clinical suspicion and flow cytometry are the keys for diagnosis of CGD and detection of carrier relatives. Specific prophylactic measures and medical controls are required to prevent serious infections. IFN-gamma has been used intermittently, though its effectiveness is controversial.

Background: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. Results: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course.

Recent studies have demonstrated a suboptimal humoral response to SARS-CoV-2 mRNA vaccines in patients diagnosed with hematologic malignancies, however data about cellular immunogenicity is scarce. In this study we aimed to evaluate both the humoral and cellular immunogenicity one month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by the Elecsys and LIAISON Anti-SARS-CoV-2 S assay while T-cell response was assessed by Interferon-Gamma-Release-immuno-Assay technology. Overall, 76.3% (184/241) of patients developed humoral immunity and the cellular response rate was 79% (184/233). Hypogammaglobulinemia, lymphopenia, active hematological treatment and anti-CD20 therapy during the last 6 months were associated with an inferior humoral response. Conversely, age over 65 years, active disease, lymphopenia and immunosuppressive treatment for GvHD were associated with an impaired cellular response. A significant dissociation between humoral and cellular response was observed in patients treated with anti-CD20 therapy, being the humoral response of 17.5% whereas the cellular response was 71.1%. In these patients B-cell aplasia was confirmed while T cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients under immunosuppressive treatment for GvHD, while only 52.4% had cellular response. The cellular and humoral response to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematological malignancies is highly influenced by the presence of treatments like anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

In this work, the effects of increasing amounts of 3 plant oils in diets on the fatty acid (FA) profile of goat milk were studied. The study consisted of 3 experiments, one per oil tested (linseed oil, LO; high oleic sunflower oil, HOSFO; and regular sunflower oil, RSFO). The 3 experiments were conducted successively on 12 Malagueña goats, which were assigned at random to 1 of 4 treatments: 0, 30, 48, and 66 (H) g of added oil/d. A basal diet made of alfalfa hay and pelleted concentrate (33:67) was used in all of the experiments. For each animal, milk samples collected after 15 d on treatments were analyzed for fat, protein, lactose, and FA composition, whereas individual milk yield was measured the last 3 d of each experiment. Oil supplementation affected neither dry matter intake nor milk production traits. Increasing the oil supplementation decreased the content of saturated FA (especially 16:0) in milk fat and increased mono- and polyunsaturated FA in a linear manner. Vaccenic acid content linearly increased with the oil supplementation by 370, 217, and 634% to 5.32, 2.66, and 5.09 g/100 g of total FA methyl esters with the H diet in LO, HOSFO, and RSFO experiments, respectively. Rumenic acid content linearly increased with LO and RSFO supplementation by 298 and 354% from 0.53 and 0.41 g/100 g of total FA methyl esters with the 0 g of added oil/d diet. The content of trans-10-18:1 was not affected by LO supplementation but showed an increasing linear trend with HOSFO supplementation and linearly increased with RSFO supplementation. The ratio of n-6 to n-3 polyunsaturated FA in milk fat was decreased by about 70% with the H diet in the LO experiment and it was increased by 54 and 82% with the H diet in the HOSFO and RSFO experiments. In conclusion, LO supplementation in this work seemed to be the most favorable alternative compared with HOSFO or RSFO supplementation.

The effect of supplementing a basal diet with 1 of 3 plant oils on productive efficiency and milk fatty acid composition was studied in dairy goats. Sixteen Malagueña goats were used in a 4×4 Latin square experiment with 21-d periods and 4 goats per treatment. The basal diet comprised 30% alfalfa hay and 70% pelleted concentrate. Experimental treatments were control (basal diet without added oil) and the basal diet supplemented with 48g/d of high oleic sunflower oil (HOSFO), regular sunflower oil (RSFO), or linseed oil (LO). Dry matter intake and body weight were not affected by treatments. Milk production was higher in HOSFO treatment and milk fat content was higher in RSFO and LO treatments, although no differences in milk energy production or milk renneting properties were found. The RSFO and LO treatments increased the proportion of vaccenic acid in milk fat more so than the HOSFO diet, and rumenic acid followed the same pattern. The content of trans10-18:1 remained low in all experimental diets (<0.7% of total fatty acid methyl esters) although HOSFO and RSFO diets increased it. The variations in the fatty acid profiles observed with the 4 diets, mainly the unsaturated fatty acid isomer contents, are extensively discussed. Compared with that in the control diet, the n-6:n-3 fatty acid ratio in milk fat substantially decreased with the LO, increased with RSFO, and did not change with HOSFO. The addition of moderate amounts of LO to the diets of dairy goats has favorable effects on milk fatty acid composition from the point of view of the human consumer, without negative effects on animal performance.

A 3 x 3 Latin Square experiment was designed to compare 2 ways of bypassing the effects of the rumen with olive oil fatty acids in 'Manchega' dairy ewes. Treatments were a control diet, CaOFA (control diet plus 45 g of olive fatty acids as calcium soap), and OO (control plus 45 g/d of olive fatty acids as olive oil emulsified in skim milk) and bottle-fed to animals trained to maintain the reticular groove reflex). No differences were found in milk, protein, and lactose yields, but fat yield and milk fat content were greater in treatments with added fat (CaOFA and OO). Content of short- and medium-chain fatty acids in milk fat was greater for control treatment than for the other 2 groups, the yield of these fatty acids being similar for all 3 diets, except that of C12:0, which was greater for the control treatment. Content and yield of C18:0 and isomers of C18:1 others than oleic acid were greater in milk from the CaOFA diet than from the other 2 diets. Oleic acid content and yield were greater in milk after OO treatment (23.9% and 16.8 g/d, respectively), intermediate after CaOFA treatment (19.2% and 13.8 g/d, respectively), and lower after control diet (10.7% and 6.52 g/d, respectively). Linoleic acid yield and content were greater in ewes fed the OO diet than in those on the other 2 diets, both of which showed similar data. All these changes indicated that the "protected" olive fatty acids (as calcium soap) were severely affected by the rumen environment and that the use of the reticular groove reflex seems to be a more effective way of bypassing the rumen in adult lactating dairy ewes.