Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Anti-Anisakis sp. antibodies in serum of patients with sepsis and their relationship with γδ T cells and disease severity.

Immunosuppression in sepsis reduces both αß and γδ T cell subsets. Anisakis sp. is a parasitic nematode with a high prevalence in Spain. Previous contact with the parasite is related to a decrease in γδ T cells. Anti-Anisakis antibodies were measured and related to αß and γδ T cells in 114 septic patients versus 97 healthy controls. Significant differences were seen with respect to the groups with severe sepsis and septic shock where lower anti-Anisakis levels were observed. A similar decrease appeared in the case of specific IgM with significant differences between the groups of control/uncomplicated sepsis versus severe sepsis and septic shock. These differences were also apparent in the case of specific IgA. The lowest IgE levels were detected in the septic shock group. Anti-Anisakis IgG levels significantly increased in septic shock groups compared with the controls. We observed positive correlations among anti-Anisakis IgA levels and all γδ T cell subsets. There were negative correlations among IgA levels and APACHE and SOFA indices. Greater contact with the parasite (IgG) was directly related with septic shock, inflammation and markers of sepsis severity. A lack of protection in the mucosa (IgA and γδ T cells) was associated with the disease severity.

B1a Lymphocytes (CD19+CD5+) Deficiency in Patients with Crohn's Disease and Its Relation with Disease Severity.

BACKGROUND/AIMS: B1a cells (CD19+CD5+) are considered elements of the innate immune system. The aim of this study was to evaluate the frequency of B1a cells in the peripheral blood of patients with Crohn's disease (CD) and its relation with disease severity. METHODS: In this prospective study, a total of 128 subjects (64 CD patients and 64 healthy controls) were studied. B1a cells in peripheral blood, CD Activity Index, and Simple Endoscopic Score of B1a cells were studied. RESULTS: A significant decrease of B1a cells in peripheral blood was observed in patients with CD versus controls (p = 0.002), especially in perforating or penetrating patterns (p = 0.017). A lower frequency of B1a cells is related to increased endoscopic severity (Spearman's Rho: -0.559, p = 0.004). The mean frequency of B1a cells in patients with pre- and post-study surgery was significantly lower than that in patients who did not undergo surgery (p = 0.050 and p = 0.026, respectively). CONCLUSIONS: The B1a cell count in peripheral blood is lower in CD patients. This decrease is directly related to the severity of the disease (penetrating or perforating, Simple Endoscopy Score and surgery complication). These results pointed to the fact that B1a cells play an important role in immune protection in CD.

Anti-Anisakis sp. antibodies in serum of healthy subjects. Relationship with αß and γδ T cells.

Anisakiosis is nowadays one of the nematodoses more prevalent in Spain, with rates that oscillate between 0.43% in Galicia (N.W. Spain), and 15.7% and 22.1% in inland and southern regions, respectively. Likewise, it has been proved that Anisakis larvae have developed mechanisms to modulate the dichotomy of the host immune response for their own benefit. The experimental hypothesis of the present study was that Anisakis sp. larval products can be mediators of immune suppression and induce changes on the populations of αß+ and γδ+ T cells. In the present study we determined the levels of anti-Anisakis antibodies in the serum of healthy people, and their relationship with the B and T cell subsets. Levels of anti-Anisakis antibodies (Ig's, IgG, IgM, IgA and IgE) were measured by ELISA, while B and T cell subsets were studied by flow cytometry. Cells were labelled with monoclonal antibodies against CD45, CD4, CD8, CD56, CD3, CD19, TCRαß and TCRγδ. All the specific isotypes studied were negatively correlated with NKT cell rates with the exception of IgG. A previous contact with Anisakis was related to a decrease in CD56+αß+ and all γδ+ T cell subsets. The CD3+γδ+ population was lower in the group of subjects that showed IgA anti-Anisakis. We observed an inverse correlation among αß-γδ NKT cells and anti-Anisakis sp. antibodies. CD3+CD56+ cells showed a significant decrease in the group of anti-Anisakis positive subjects. This fact was especially significant with CD3+CD56+γδ+ cells in the case of the anti-Anisakis IgA positive group.

BCL6: somatic mutations and expression in early-stage chronic lymphocytic leukemia.

BCL6 somatic mutations affect normal and tumoral post germinal center B-lymphocytes. Our objective was to analyse expression, mutations and polymorphisms in the BCL6 gene and to correlate those variables with the clinical outcome in early-stage chronic lymphocytic leukemia (CLL). CLL samples were used for characterisation of the mutational status of BCL6/ immunoglobulin variable heavy chain (IGHV) genes, and expression of BCL6 was determined by real time PCR and immunoblot. Out of 68 cases, 29% show somatic mutations on BCL6 which occur exclusively in IGHV mutated cases. They are single nucleotide substitutions located mainly in two short mutational hot spots. CLL cells express different levels of BCL6 regardless of the mutational status, the number of mutations and polymorphisms. CLL cases expressing high levels of BCL6 have significantly shorter treatment-free interval. In conclusion, in early-stage patients with CLL, we found no correlation between expression and the mutations or polymorphism in BCL6, but high levels of BCL6 can discriminate patients with a worse prognosis.