Bone Marrow Failure due to Aplastic Anemia, Associated With Serous Fat Atrophy, and Treated With Allogeneic, Haploidentical Stem Cell Transplantation: A Case Report.

We describe the case of a 27-year-old male, previously healthy though with a social history notable for recreational cocaine use, who developed bone marrow failure due to aplastic anemia (AA) with associated serous fat atrophy (SFA). After the SFA was corrected with nutritional supplementation, the patient underwent successful allogeneic, haploidentical stem cell transplantation with a regimen designed to treat AA. To our knowledge, this is the first case of hematopoietic stem cell transplantation (HSCT) performed following correction of SFA.

Characteristics of isatuximab-derived interference in serum protein electrophoresis and immunofixation, and an absence of sustained in vivo interference due to belantamab mafodotin and denosumab.

Objectives: Some therapeutic monoclonal antibodies, like daratumumab and elotuzumab, produce interfering monoclonal bands on serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). Whether other common therapeutic antibodies also produce interference has not been systematically evaluated.

Design And Methods: SPEP/IFE from patients receiving isatuximab (48 patients), belantamab mafodotin (BM; 41), and denosumab (41) were retrospectively reviewed for therapeutic antibody interference.

Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma.

Introduction: Our previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center.

Methods: We collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations.

The Distinctive Nature of Thyroid MALT Lymphomas Including IRTA1 Expression.

Mucosa-associated lymphoid tissue (MALT) lymphomas often express IgM and IRTA1 with only a minority demonstrating plasmacytic differentiation. However, like primary cutaneous marginal zone lymphoproliferative disorders (PCMZLPD), thyroid MALT lymphomas (T-MALT-L) frequently show plasmacytic differentiation and IgG positivity. Whether T-MALT-L share other features with PCMZLPD, including frequent IgG4 positivity and infrequent IRTA1 expression, and how IRTA1 staining compares to that in Hashimoto thyroiditis (HT) are unknown.

Characterization of Casirivimab Plus Imdevimab, Sotrovimab, and Bamlanivimab Plus Etesevimab-Derived Interference in Serum Protein Electrophoresis and Immunofixation Electrophoresis.

Background: Therapeutic monoclonal antibodies can be a source of assay interference in clinical serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE), producing monoclonal bands that can be misinterpreted as a monoclonal gammopathy related to a B-cell or plasma cell neoplasm. The extent to which new anti-COVID-19 monoclonal antibodies produce this interference is unknown.

Methods: Casirivimab plus imdevimab, sotrovimab, and bamlanivimab plus etesevimab were spiked into patient serum samples to evaluate for SPEP/IFE interference, to characterize the position of therapy-derived bands relative to a reference band (either combined beta band or beta 1 band, depending on instrument platform), and to confirm heavy and light chain utilization of each medication.

IRTA1 positivity helps identify a MALT-lymphoma-like subset of primary cutaneous marginal zone lymphomas, largely but not exclusively defined by IgM expression.

Background: It has been proposed that primary cutaneous marginal zone lymphomas (PCMZLs) include a MALT-lymphoma-like IgM+ subset and a class-switched subset, which is unlike most other MALT lymphomas. Whether expression of the MALT lymphoma-associated biomarkers IRTA1 and MNDA would support this concept and whether they might help explain why some patients have both subtypes is uncertain.

Methods: Twenty-five PCMZLs from 21 patients were stained for IRTA1 by in situ hybridization and for MNDA by immunohistochemistry.

Class-switched Primary Cutaneous Marginal Zone Lymphomas Are Frequently IgG4-positive and Have Features Distinct From IgM-positive Cases.

Primary cutaneous marginal zone lymphoma (PCMZL) can be subdivided into 2 groups based on immunoglobulin (Ig) heavy chain usage: IgM-positive cases that constitute a less common and more T-helper type 1-driven process, and more common heavy chain class-switched cases that are predominantly T-helper type 2-driven. Although some report a significant IgG4-positive subset, others have found a much smaller proportion. To further evaluate the proportion of IgG4-positive PCMZL, to address whether IgG4-positive cases have any distinctive characteristics, and to assess whether additional features separating IgM-positive and class-switched cases could be identified, the clinicopathologic features of 26 PCMZL obtained from 19 patients were investigated.

NF2 and ATRX gene copy number losses on a case of ovarian ependymoma.

Ovarian ependymomas are rare glial neoplasms that typically occur in women on their third to fourth decades of life. They are histologically similar to ependymomas of the central nervous system but may have a broader immunophenotype. We describe a 27-year-old woman who presented to the emergency department with a 3-week history of cough and shortness of breath.

mTOR Mediates IL-23 Induction of Neutrophil IL-17 and IL-22 Production.

It has been shown recently that neutrophils are able to produce IL-22 and IL-17, which differentially regulate the pathogenesis of inflammatory bowel disease. However, it is still largely unknown how the neutrophil production of IL-22 and IL-17 is regulated, and their role in the pathogenesis of inflammatory bowel disease. In this study, we found that IL-23 promoted neutrophil production of IL-17 and IL-22.

Interactions between Neutrophils and Leishmania braziliensis Amastigotes Facilitate Cell Activation and Parasite Clearance.

Leishmania braziliensis and Leishmania amazonensis are both causative agents of cutaneous leishmaniasis in South America. However, patient prognosis and the host immune response differ considerably depending on the infecting parasite species. The mechanisms underlying these differences appear to be multifactorial, with both host and parasite components contributing to disease outcome.

Leishmania amazonensis amastigotes highly express a tryparedoxin peroxidase isoform that increases parasite resistance to macrophage antimicrobial defenses and fosters parasite virulence.

Professional phagocytes generate a myriad of antimicrobial molecules to kill invading microorganisms, of which nitrogen oxides are integral in controlling the obligate intracellular pathogen Leishmania. Although reactive nitrogen species produced by the inducible nitric oxide synthase (iNOS) can promote the clearance of intracellular parasites, some Leishmania species/stages are relatively resistant to iNOS-mediated antimicrobial activity. The underlying mechanism for this resistance remains largely uncharacterized.

Downregulation of microRNA-107 in intestinal CD11c(+) myeloid cells in response to microbiota and proinflammatory cytokines increases IL-23p19 expression.

Commensal flora plays an important role in the development of the mucosal immune system and in maintaining intestinal homeostasis. However, the mechanisms involved in regulation of host-microbiota interaction are still not completely understood. In this study, we examined how microbiota and intestinal inflammatory conditions regulate host microRNA expression and observed lower microRNA-107 (miR-107) expression in the inflamed intestines of colitic mice, compared with that in normal control mice.

Hepatocyte growth factor in dampening liver immune-mediated pathology in acute viral hepatitis without compromising antiviral activity.

Background And Aim: Hepatocyte growth factor (HGF) is a pleiotropic cytokine related with cell proliferation and survival; however, its role in viral hepatitis is not elucidated. In this study, we studied HGF immune role in viral hepatitis.

Methods: Mice received hydrodynamically delivered HGF plasmid or control plasmid and then infected with adenovirus, and parameters of immune-mediated liver damage were evaluated.

Immunomodulatory and antibacterial effects of cystatin 9 against Francisella tularensis.

Cystatin 9 (CST9) is a member of the type 2 cysteine protease inhibitor family, which has been shown to have immunomodulatory effects that restrain inflammation, but its functions against bacterial infections are unknown. Here, we report that purified human recombinant (r)CST9 protects against the deadly bacterium Francisella tularensis (Ft) in vitro and in vivo. Macrophages infected with the Ft human pathogen Schu 4 (S4), then given 50 pg of rCST9 exhibited significantly decreased intracellular bacterial replication and increased killing via preventing the escape of S4 from the phagosome.

Leishmania amazonensis amastigotes trigger neutrophil activation but resist neutrophil microbicidal mechanisms.

Neutrophils are the first cells to infiltrate to the site of Leishmania promastigote infection, and these cells help to reduce parasite burden shortly after infection is initiated. Several clinical reports indicate that neutrophil recruitment is sustained over the course of leishmaniasis, and amastigote-laden neutrophils have been isolated from chronically infected patients and experimentally infected animals. The goal of this study was to compare how thioglycolate-elicited murine neutrophils respond to L.

Differential microbicidal effects of human histone proteins H2A and H2B on Leishmania promastigotes and amastigotes.

Recent studies have shown that histone proteins can act as antimicrobial peptides in host defense against extracellular bacteria, fungi, and Leishmania promastigotes. In this study, we used human recombinant histone proteins to further study their leishmaniacidal effects and the underlying mechanisms. We found that the histones H2A and H2B (but not H1(0)) could directly and efficiently kill promastigotes of Leishmania amazonensis, L.