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Multidimensional flow cytometry (MFC) is routinely used for the diagnosis and follow‐up of hematolymphoid neoplasms but its contribution to the identification of non‐hematolymphoid malignant tumors is limited. The presence of non‐hematolymphoid cells in clinical samples obtained via minimally invasive methods was ascertained by using a panel of monoclonal antibodies previously developed in our laboratory comprising a mixture of antibodies: CD9‐PacB/CD45‐OC515/CD57‐FITC/CD56‐PE/CD3‐PerCP‐Cy5.5/CD117‐PE‐Cy7/CD326‐APC/CD81‐APC‐C750. Histopathological studies were performed using standard techniques. 164 specimens of different origins were included. Malignancy was finally confirmed in 142 (86.5%), while 22 non neoplastic samples were identified. The most frequent diagnosis was small cell lung carcinoma (SCLC) (50%). High sensitivity (S = 98.6%) was reached combining MFC and conventional pathology. Individual markers differed according to the cellular origin of the neoplasm, with neuroendocrine tumors showing a unique immunophenotypic profile (CD56+ CD326+ CD117−/+ and variable tetraspanins expression). Principal component analysis efficiently distinguished SCLC from other tumor samples. In immune cell populations, differences between reactive and malignant biopsies were found in different cell compartments, especially in B cells and Plasma cells. Differences also emerged in the percentage of CD4+ CD8− T cells, CD4‐CD8+ T cells and NK cells and these were dependent on the origin of the tumor cells. These results support the use of MFC as a rapid and valuable technique to detect non‐hematolymphoid tumoral cells in clinical specimens, providing an initial orientation to complement hystopathological studies and allow a more precise diagnosis, especially in neuroendocrine neoplasms. The impact of different immune cell patterns warrants further research.

Large genome-wide analysis studies (GWAS) and meta-analyses have dramatically increased our knowledge of the genetic risk factors of inflammatory bowel disease (IBD), identifying at least 163 loci. The endoplasmic reticulum aminopeptidase-2 (ERAP2) gene has been reported as a potential candidate gene for IBD. GWAS have also shown the potential associations between ERAPsingle nucleotide polymorphisms (SNP) loci and susceptibility to several autoimmune diseases, and ERAP1and ERAP2polymorphisms are related to HLA class I-associated diseases, including ankylosing spondylitis and Behçet’s disease. Interestingly, these associations were confined to individuals carrying HLA class I-risk alleles. The aim of this study was to investigate the association of ERAP1and ERAP2SNPs with IBD in a Spanish population, analysing their possible interaction with specific HLA-C alleles to IBD susceptibility. A total of 367 individuals were divided into 216 IBD cases and 151 controls. SNP genotyping was performed using TaqMan® genotyping assays, whereas HLA-C typing was analysed by sequence-specific oligonucleotide probing. Herein, we report an association of the ERAP1SNP rs30187 with the HLA-C*07 allele. The existence of shared inflammatory pathways in immunologically related diseases together with the understanding of ERAP1 function may offer clues to novel treatment strategies.

IL‐15 and IL‐21 have similar effects on CD4+CD28nulland CD4+CD28nullT lymphocytes in HIV‐infected patients, both on resting and TCR‐activated cells. HIV‐infected individuals suffer from accelerated immunologic aging. One of the most prominent changes during T lymphocyte aging is the accumulation of CD28nullT lymphocytes, mainly CD8+but also CD4+T lymphocytes. Enhancing the functional properties of these cells may be important because they provide antigen‐specific defense against chronic infections. The objective of this study was to compare the responses of CD4+CD28nulland CD8+CD28nullT lymphocytes from HIV‐infected patients to the immunomodulatory effects of cytokines IL‐15 and IL‐21. We quantified the frequencies of CD4+CD28nulland CD8+CD28nullT lymphocytes in peripheral blood from 110 consecutive, HIV‐infected patients and 25 healthy controls. Patients showed increased frequencies of CD4+CD28nulland CD8+CD28null. Both subsets were positively correlated to each other and showed an inverse correlation with the absolute counts of CD4+T lymphocytes. Higher frequencies of HIV‐specific and CMV‐specific cells were found in CD28nullthan in CD28+T lymphocytes. Activation of STAT5 by IL‐15 and STAT3 by IL‐21 was higher in CD28nullcompared with CD28+T lymphocytes. Proliferation, expression of CD69, and IFN‐γ production in CD28nullT lymphocytes were increased after treatment with IL‐15, and IL‐21 potentiated most of those effects. Nevertheless, IL‐21 alone reduced IFN‐γ production in response to anti‐CD3 stimulation but increased CD28 expression, even counteracting the inhibitory effect of IL‐15. Intracytoplasmic stores of granzyme B and perforin were increased by IL‐15, whereas IL‐21 and simultaneous treatment with the 2 cytokines also significantly enhanced degranulation in CD4+CD28nulland CD8+CD28nullT lymphocytes. IL‐15 and IL‐21 could have a role in enhancing the effector response of CD28nullT lymphocytes against their specific chronic antigens in HIV‐infected patients.

INTRODUCTION.Chromosome banding analysis (CBA) is the gold standard to identify complex karyotypes (CK; ≥3 chromosomal aberrations in the same clone). CK are predictors of poor prognosis and treatment refractoriness in patients with chronic lymphocytic leukemia (CLL). Patients with CK (15% at diagnosis) constitute a heterogeneous subgroup with highly variable clinical course. Recent studies that aim to refine CK definition in CLL suggest that ≥5 is the number of anomalies detected by CBA that better predicts an impaired outcome (Baliakas et al, 2019). Molecular techniques as genomic microarrays also detect genomic complexity (GC). A recent multicentric ERIC study (Leeksma et al, ASH 2017) identified that patients with ≥5 copy number alterations (CNA) detected by microarrays are associated with an adverse outcome. However, risk stratification regarding genomic complexity assessed by CBA and microarrays has not been compared.

Rigolin: AbbVie: Speakers Bureau; Gilead: Speakers Bureau; Gilead: Research Funding. Gimeno:JANSSEN: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Bosch:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AstraZeneca: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Cuneo:Amgen: Honoraria; Abbvie: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.