Gamma-delta T-cell large granular lymphocytic leukemia in the setting of rheumatologic diseases

BackgroundT-cell leukemia originating from large granular lymphocytes (T-LGL leukemia) is a rare lymphoid neoplasia characterized by clonal proliferation of large granular T lymphocytes expressing αβ or γδ T-cell receptor (TCR) on the cell membrane. γδT-LGL leukemia, accounting for approximately 17% of all T-LGL leukemia cases, is associated with autoimmune diseases. However, the features of γδT-LGL leukemia in patients with rheumatologic diseases are still insufficiently characterized.MethodsIn this retrospective study, 15 patients with rheumatologic disease-associated γδT-LGL leukemia were included. The patients were obtained from a single center from 2008 to 2023. Data related to clinical characteristics and rheumatologic diagnoses were collected. Immunophenotype evaluations as well as T-lymphocyte clonality (based on TCR-γ, TCR-β, and TCR-δ gene rearrangements), and signal transducer and activator of transcription (STAT) three and STAT5B mutation analyses (by next-generation sequencing) were performed on blood, bone marrow, and spleen samples.ResultsAll but one patient had rheumatoid arthritis (RA). In 36% of patients, manifestations of γδT-LGL leukemia were present before or concurrently with clinical manifestations of RA. Splenomegaly was observed in 60% of patients and neutropenia (<1.5 × 109/L) was detected in 93% of cases. CD4−/CD8− and CD4−/CD8+ subtypes were detected in seven cases each. Mutations in STAT3 were detected in 80% of patients; however, STAT5B mutations were not detected. Evaluations of T-cell clonality and variant allele frequencies at STAT3 in the blood, bone marrow, and spleen tissue revealed an unusual variant of CD4−/CD8− γδT-LGL leukemia with predominant involvement of the spleen, involvement of the bone marrow to a less extent, and no tumor cells in peripheral blood.ConclusionThe mechanism by which γδT-LGL leukemia may induce the development of RA in some patients requires further investigation. Cases of RA-associated γδT-LGL leukemia with neutropenia and splenomegaly but no detectable tumor-associated lymphocytes in peripheral blood (the so-called splenic variant of T-LGL leukemia) are difficult to diagnose and may be misdiagnosed as Felty syndrome or hepatosplenic T-cell lymphoma

How to Avoid False-Negative and False-Positive COVID-19 PCR Testing

Background: Up to 40% of test results for COVID-19 in the presence of clinical manifestations of the disease might be negative. The reason for a false-negative result might originate from any step of the analysis: poor-quality or empty swab, poor RNA isolation, inactivation of reverse transcriptase or Taq polymerase in the test. Methods: Here we describe a PCR approach for SARS-CoV-2 detection with swab quality and integrity controlled by human ABL1 mRNA amplification. Designed primers work with the cDNA of the ABL1 gene, not genomic DNA. Results: The simultaneous appearance of three signals corresponding to the nucleocapsid, spike, and ABL1 gene indicates infection with the Omicron strain. The amplification of ABL1 gene and nucleocapsid only indicate other than Omicron infection. The appearance of ABL1 amplification only indicates a true negative result for SARS-CoV-2. All other variants are null and void. Conclusions: A system has been developed for multiplex PCR diagnostics of SARS-CoV-2, which makes it possible to eliminate errors leading to false-negative and false-positive results at all stages of analysis. This is accomplished by the presence of specific primers for human RNA, controlling proper swab application, handling, and all the stages of RT-PCR

Features of Microstructure and Texture Formation of Large-Sized Blocks of C11000 Copper Produced by Electron Beam Wire-Feed Additive Technology

The paper investigated the possibility of obtaining large-sized blocks of C11000 copper on stainless steel substrates via electron beam wire-feed additive technology. The features of the microstructure and grain texture formation and their influence on the mechanical properties and anisotropy were revealed. A strategy of printing large-sized C11000 copper was determined, which consists of perimeter formation followed by the filling of the internal layer volume. This allows us to avoid the formation of defects in the form of drops, underflows and macrogeometry disturbances. It was found that the deposition of the first layers of C11000 copper on a steel substrate results in rapid heat dissipation and the diffusion of steel components (Fe, Cr and Ni) into the C11000 layers, which promotes the formation of equiaxed grains of size 8.94 ± 0.04 μm. As the blocks grow, directional grain growth occurs close to the <101> orientation, whose size reaches 1086.45 ± 57.13 μm. It is shown that the additive growing of large-sized C11000 copper leads to the anisotropy of mechanical properties due to non-uniform grain structure. The tensile strength in the opposite growing direction near the substrate is 394 ± 10 MPa and decreases to 249 ± 10 MPa as the C11000 blocks grows. In the growing direction, the tensile strength is 145 ± 10 MPa

Clinical Study of the Relationship between Sjögren Syndrome and T-Cell Large Granular Lymphocytic Leukemia: Single-Center Experience

The relationship between Sjögren syndrome (SS) and T-cell large granular lymphocytic (T-LGL) leukemia remains unclear. In this paper, we report for the first time a large case series of 21 patients with primary and secondary SS associated with T-LGL leukemia. Our results suggest the importance of considering T-LGL leukemia in the diagnostic evaluation of SS patients, particularly when neutropenia occurs. We also postulate that elevated antinuclear antibody titers in patients with T-LGL leukemia indicate the need for the clinical assessment of SS. To assess whether SS affects the frequency of the signal transducer and activator of transcription 3 (STAT3) gene mutations in T-LGL leukemia, we examined STAT3 mutations by next-generation sequencing in two cohorts of patients: with SS-associated T-LGL leukemia and T-LGL leukemia in the setting of rheumatic diseases but without SS. While our results suggest that SS, per se, is not associated with an increased frequency of STAT3 mutations in T-LGL leukemia, further studies are needed to better assess the role of the STAT pathway in the development of concomitant SS and T-LGL leukemia

In-Situ Al-Mg Alloy Base Composite Reinforced by Oxides and Intermetallic Compounds Resulted from Decomposition of ZrW₂O₈ during Multipass Friction Stir Processing

In the presented work, the effect of friction stir processing admixing the zirconium tungstate ZrW2O8 powder on the microstructure, mechanical and tribological properties of the AA5056 Al-Mg alloy stir zone has been studied. The FSP resulted in obtaining dense composite stir zones where α-ZrW2O8 underwent the following changes: (i) high-temperature transformation into metastable β’-ZrW2O8 and (ii) decomposition into WO3 and ZrO2 oxides followed by the formation of intermetallic compounds WAl12 and ZrAl3. These precipitates served as reinforcing phases to improve mechanical and tribological characteristics of the obtained fine-grained composites. The reduced values of wear rate and friction coefficient are due to the combined action the Hall–Petch mechanism and reinforcement by the decomposition products, including Al2O3, ZrO2, β’-ZrW2O8 and intermetallic compounds such as WAl12 and ZrAl3. Potential applications of the above-discussed composites maybe related to their improved tribological characteristics, for example in aerospace and vehicle-building industries