Indolent natural killer (NK) cell lymphoproliferative disorders include a heterogeneous group of patients in whom persistent expansions of mature, typically CD56 ؉ , NK cells in the absence of any clonal marker are present in the peripheral blood. In the present study we report on the clinical, hematological, immunophenotypic, serological, and molecular features of a series of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells were either CD56 ؊ or expressed very low levels of CD56 (CD56 ؊/؉dim NK cells), in the context of an aberrant activation-related mature phenotype and proved to be monoclonal using the human androgen receptor gene polymerase chain reaction-based assay. As normal CD56 ؉ NK cells, CD56 ؊/؉dim NK cells were granzyme B ؉ , CD3 ؊ , TCR␣␤/ ␥␦ ؊ , CD5 ؊ , CD28 ؊ , CD11a ؉bright , CD45RA ؉bright , CD122 ؉ , and CD25 ؊ and they showed variable and heterogeneous expression of both CD8 and CD57. Nevertheless, they displayed several unusual immunophenotypic features. Accordingly, besides being CD56 ؊/؉dim , they were CD11b ؊/؉dim (heterogeneous), CD7 ؊/؉dim (heterogeneous), CD2 ؉ (homogeneous), CD11c ؉bright (homogeneous), and CD38 ؊/؉dim (heterogeneous). Moreover, CD56 ؊/؉dim NK cells heterogeneously expressed HLA-DR. In that concerning the expression of killer receptors, CD56 ؊/؉dim NK cells showed bright and homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161, whereas CD158a and NKB1 expression was variable. From the functional point of view, CD56 ؊/؉dim showed a typical Th1 pattern of cytokine production (interferon-␥ ؉ , tumor necrosis factor-␣ ؉ ). From the clinical point of view, these patients usually had an indolent clinical course, progression into a massive lymphocytosis with lung infiltration leading to death being observed in only one case. Despite this, they frequently had associated cytopenias as well as neoplastic diseases and/or viral infections. In summary, we describe a unique and homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with an aberrant activation-related CD56 ؊/؉dim /CD11b ؊/؉dim phenotype and an indolent clinical course, whose main clinical features are related to concomitant diseases. (Am J

Intramammary infections (IMI) with Staphylococcus aureus are a common cause of bovine mastitis and can result in both clinical (CM) or subclinical mastitis (SCM). Although bacterial isolates of S. aureus differ in their virulence potential it is largely unclear which bacterial virulence factors are responsible for increased clinical severity. We performed a genome wide association study and used a generalized linear mixed model to investigate the correlation between gene carriage, lineage and clinical outcome of IMI in a collection of S. aureus isolates from cattle with CM (n = 125) and SCM (n = 151) from 11 European countries. An additional aim was to describe the genetic variation of bovine S. aureus in Europa. The dominant lineages in our collection were clonal complex (CC) 151 (81/276, 29.3%), CC97 (54/276, 19.6%), CC479 (32/276, 11.6%) and CC398 (19/276, 6.9%). Virulence and antimicrobial resistance (AMR) gene carriage was highly associated with CC. Among a selection of nine virulence and AMR genes, CC151, CC479 and CC133 carried more virulence genes than other CCs, and CC398 was associated with AMR gene carriage. Whereas CC151, CC97 were widespread in Europe, CC479, CC398 and CC8 were only found in specific countries. Compared to CC151, CC479 was associated with CM rather than SCM (OR 3.62; 95% CI 1.38–9.50) and the other CCs were not. Multiple genes were associated with CM, but due to the clustering within CC of carriage of these genes, it was not possible to differentiate between the effect of gene carriage and CC on clinical outcome of IMI. Nevertheless, this study demonstrates that characterization of S. aureus CC and virulence genes helps to predict the likelihood of the occurrence of CM following S. aureus IMI and highlights the potential benefit of diagnostics tools to identify S. aureus CC during bovine mastitis.

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ABSTRACT:We describe the immunophenotypic and gross DNA defects in 55 patients with myeloma and 50 patients with monoclonal gammopathy and review the literature on this subject (MedLine, 1994(MedLine, -2000. Our data confirmed previous reports indicating that in myeloma nearly all marrow plasma cells are abnormal (98.7 Ϯ 8.1%). In monoclonal gammopathy the fraction of abnormal plasma cells was 35.0 Ϯ 32.8%. In both myeloma and monoclonal gammopathy, the most frequent aberrant phenotypic features consisted of absence of expression of CD19, strong expression of CD56, and decreased intensity of expression of CD38; aberrant expression of CD10, CD20, CD22, or CD28 was observed in less than one-third of myeloma cases. The vast majority of cases had two or more phenotypic aberrations. In the DNA studies, 7% of myeloma cases were biclonal and 93% of cases were monoclonal. In those studies with only one plasma cell mitotic cycle, 37% had normal DNA content and 63% were aneuploid (hyperploid, 61%; hypoploid, 2%). The mean percentages of plasma cells in S-and G2M phases were 4.9 Ϯ 8.5 and 4.4 Ϯ 6.9%, respectively. Thirty-eight percent of cases had more than 3% of plasma cells in S phase. In monoclonal gammopathy, the DNA index of abnormal plasma cells ranged from 0.89 to 1.30 and the percentage of diploid (31%) and aneuploid (69%) cases was not different from the results found in myeloma. The differences in percentage of abnormal plasma cells in S-(7.4 Ϯ 8.6%) and G2M-phases (2.4 Ϯ 1.7%) in patients with monoclonal gammopathy were not statistically significant.

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