Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.
Male ; Female ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Lymphoma, T-Cell, Peripheral/pathology* ; Killer Cells, Natural/pathology* ; Prognosis ; Immunophenotyping

Objective: To investigate the clinicopathological characteristics and prognosis of mature T/NK cell lymphomas with aberrant CD20 or CD79α expression. Methods: A retrospective analysis of 641 cases of mature T/NK cell lymphoma diagnosed from January 2014 to December 2020 was performed, and 14 cases of CD20-positive and one case of CD79α-positive mature T/NK-cell lymphoma were identified. Histological examination, immunohistochemical characterization, in situ hybridization for Epstein-Barr virus encoded early RNA (EBER), and PCR testing for immunoglobulin and T cell receptor (TCR) gene rearrangements were performed. Clinicopathological characteristics of these lymphomas were analyzed. Results: There were 13 males and 2 females, with a median age of 56 years. There were 8 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 3 cases of extranodal NK/T-cell lymphoma, nasal type (ENKTCL), 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and 2 cases of angioimmunoblastic T-cell lymphoma (AITL). Twelve cases were stage Ⅲ or Ⅳ lymphomas. The prognosis was overall poor. The histology, immunophenotype and TCR gene rearrangement were not significantly different from the corresponding types of lymphoma. Ki-67 proliferation index was over 70% in all cases. The expression of CD20 or CD79α was weak and heterogeneous. All 15 case of Ig gene rearrangement were polyclonal. Conclusions: Mature T/NK cell lymphoma with abnormal expression of CD20 or CD79α is rare, commonly found in advanced stage, and associated with poor prognosis. The expression of CD20 or CD79α in these cases is weaker than the corresponding mature T/NK cell lymphomas, while its proliferation index is higher. Histomorphology, extensive immunoprofiling and molecular detection are required for accurate diagnosis.
Antigens, CD20 ; Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human/genetics* ; Humans ; Killer Cells, Natural/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Male ; Middle Aged ; Receptors, Antigen, T-Cell ; Retrospective Studies

Objective To explore the clinical and laboratory characteristics and the prognosis of disseminated non-tuberculous mycobacteria(NTM)diseases in human immunodeficiency virus(HIV)negative patients. Methods Cases of disseminated NTM disease were retrospectively collected in Peking Union Medical College Hospital from January 2012 to October 2018.Clinical manifestations,laboratory findings,treatment,and prognosis of these cases were retrieved from the electronic medical record system. Results Among the 23 HIV negative patients with disseminated NTM disease,21 had underlying diseases,with rheumatoid immune disease(n=7)as the most common one.The main clinical manifestation was fever(n=23).Laboratory tests showed anemia [hemoglobin(85.78±25.47)g/L],hypoalbuminemia [albumin 29(27-32)g/L],elevated erythrocyte sedimentation rate [(85.73±43.78)mm/h] and hypersensitive C-reactive protein [(112.00±70.90)mg/L],and reduction of lymphocyte count [0.69(0.29-2.10)×10 /L].Lymphocyte subset analysis indicated reduction in CD4 T cells [213(113-775)/μl],CD8 T cells [267(99-457)/μl],B cells [39(4-165)/μl],and NK cells [88(32-279)/μl] and elevation of human leukocyte antigen-D related(HLA-DR),and CD38 expression in CD8 T cells [HLA-DR CD8 /CD8 ,60(40-68)%;CD38 CD8 /CD8 ,81(65-90)%].The most common species of NTM was Mycobacterium intracellular(n=6).Lymphocyte,CD8 T cell,B cell,and NK cell counts were significantly lower in dead patients than surviving patients(P =0.045,P=0.045,P=0.032,and P=0.010,respectively). Conclusions Disseminated NTM disease in HIV negative patients is mainly manifested as fever,anemia,hypoalbuminemia,and elevated inflammatory indicators.It is more likely to occur in immunocompromised patients.Patients with decreased lymphocytes,CD8 T cells,B cells and NK cells tend to have a poor prognosis.
Anemia ; B-Lymphocytes ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Fever ; HIV Seronegativity ; Humans ; Hypoalbuminemia ; Killer Cells, Natural ; Mycobacterium Infections, Nontuberculous ; diagnosis ; pathology ; Prognosis ; Retrospective Studies

Natural killer cells (NKs) have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells (PBMCs), stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.
Humans ; Immunotherapy ; methods ; Killer Cells, Natural ; immunology ; Neoplasms ; pathology ; therapy ; Treatment Outcome

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.
Animals ; Autoimmune Diseases ; immunology ; Humans ; Liver ; pathology ; Liver Diseases ; immunology ; Natural Killer T-Cells ; immunology

No abstract available.
Asian Continental Ancestry Group/*genetics ; Base Sequence ; Bone Marrow Cells/cytology/pathology ; Cytomegalovirus Infections/diagnosis ; Epstein-Barr Virus Infections/diagnosis ; Female ; Flow Cytometry ; Heterozygote ; Humans ; Infant ; Killer Cells, Natural/cytology/immunology ; Lymphohistiocytosis, Hemophagocytic/*diagnosis/genetics ; Perforin/*genetics ; Phagocytosis ; Polymorphism, Single Nucleotide ; Republic of Korea ; Sequence Analysis, DNA

Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer (NK) cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in β-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors (NKG2A, CD158a, NKP30, NKP46 and NKG2D) as well as CD107a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity (CD107a expression) of circulating NK cells in transfusion-dependent β-thalassemia major patients were remarkably lower than those of β-thalassemia minor patients or healthy volunteers. Expression of NKG2A inhibitory receptor on circulating NK cells in patients with β-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2D, CD158a and IFN-γ. These results indicate NKG2A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with β-thalassemia major.
Adolescent ; Child ; Female ; Flow Cytometry ; Gene Expression Regulation ; Humans ; Immunosuppression ; Killer Cells, Natural ; immunology ; metabolism ; Male ; NK Cell Lectin-Like Receptor Subfamily C ; blood ; immunology ; NK Cell Lectin-Like Receptor Subfamily K ; blood ; immunology ; Natural Cytotoxicity Triggering Receptor 1 ; blood ; immunology ; Natural Cytotoxicity Triggering Receptor 3 ; blood ; immunology ; Receptors, KIR2DL1 ; blood ; immunology ; Transfusion Reaction ; beta-Thalassemia ; blood ; immunology ; pathology

Immune thrombocytopenia (ITP) is recognized as a multifactorial cell-specific autoimmune disorder, and its pathogenesis is still not very clear. Traditional concept suggests that the platelet destruction mediated by autoantibodies is the pathophysiology mechanism of ITP, while many studies in recent years have shown that the abnormities of T lymphocyte, dendritic cell (DC), natural killer cell (NK), cytokine, programmed cell death (PCD), oxidative stress (OS), infection, pregnancy and drugs etc play an important role in the pathogenesis of ITP. Since the study of ITP has made a series of important achievements in recent years, this review focuses on the latest advance of studies on pathogenesis of ITP.
Apoptosis ; Autoantibodies ; blood ; Cytokines ; blood ; Dendritic Cells ; pathology ; Humans ; Killer Cells, Natural ; pathology ; Oxidative Stress ; Purpura, Thrombocytopenic, Idiopathic ; physiopathology ; T-Lymphocytes ; pathology

OBJECTIVESevere Epstein-Barr (EB) virus infection is potentially a devastating process that often leads to death encountered in pediatrics recently. Inappropriate control of EB virus replication may cause severe infection resulting in multiple organ dysfunction. However, little information is available on pulmonary complications associated with EB virus infection. The aim of the present study was to investigate severe EB virus (EBV) infection complicated with lung injury in pediatric intensive care unit (PICU), including clinical characteristics, laboratory or imaging feature and outcomes.

METHODA total of 45 children with severe EBV infection seen in PICU of Shanghai Children's Hospital between January 2011 and December 2014 were retrospectively reviewed. According to clinical characteristics and imaging feature, 45 children were divided into non-lung injury group (n =27), lung injury without pulmonary fibrosis group(n = 12) and pulmonary fibrosis group (n = 6).

RESULTIn totally 45 cases of severe EBV infection, 21 (46.7%) were male and 24 (53. 3%) were female, mean age was 2. 4 years; 18 cases were complicated with lung injury, including 8 male and 10 female, median age was 31. 2 months. All of 18 cases presented with fever and cough, 15 of them exhibited dyspnea,12 cases were complicated with gasping, and 6 cases with ARDS. Eight cases accepted mechanical ventilation for acute respiratory distress; 6 cases who developed pulmonary fibrosis had tachypnea, refractory hypoxemia and hypercapnia, severe pulmonary air leak. The average EBV-DNA level in peripheral blood was 4. 42 x 10(6) copies/ml (range: 3. 25 x 10(3) - 6.59 x 10(7) copies/ml). Anti-EBV antibodies were positive in 41 cases, 18 cases were positive (+) for VCA-IgM, 15 cases were VCA-IgG and EA-IgG (+), 8 cases VCA-IgM and VCA-IgG (+). The radiographic findings revealed pulmonary interstitial infiltrates in all 18 cases with lung injury, 4 cases with segmental consolidation and 2 cases showed pleural effusions. HRCT scanning found EBV associated fibrosis including multifocal patches and diffuse ground-glass attenuation in both lungs, reticular opacities and honeycombing changes were observed 4 weeks after illness onset. There were significant differences in respiratory failure, PICU stay (days), Pediatric risk of mortality III (PRISM III) and pediatric clinical illness score(PCIS), serum TNF-α, EBV-DNA levels, percentage of NK cells and CD4+/CD8+ T cell ratio among non-lung injury group, lung injury without pulmonary fibrosis group and pulmonary fibrosis group (X2 =27. 12, F = 85. 23, 78. 23, 88. 68, 323. 80, 7. 35, χ2 = 6. 71, 12. 15; all P < 0. 05). COX regression analysis revealed that EBV-DNA and serum TNF-α levels were correlated with pulmonary fibrosis significantly (OR = 3. 92, P = 0. 04; OR = 5. 95, P = 0. 01). The patients with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) had higher incidence of pulmonary fibrosis compared with non-EB-HLH (70% vs. 13%, χ2 = 4. 82, P = 0. 03). Of 18 cases, 8 cases died, including 3 cases with pulmonary fibrosis. The surviving cases with pulmonary fibrosis needed longer additional oxygen. Chest HRCT imaging of 3 cases with pulmonary fibrosis was improved at 6 months and oxygen therapy was discontinued at 18 months after discharge.

CONCLUSIONEB virus infection complicated with lung injury had higher incidence of respiratory failure, pulmonary fibrosis with a fatal outcome. EBV-DNA and serum TNF-α level were found to be statistically significant indicators of pulmonary fibrosis. Pulmonary fibrosis associated with severe EB virus infection may be reversible.

Antibodies, Viral ; blood ; CD4-CD8 Ratio ; Child, Preschool ; China ; DNA, Viral ; blood ; Epstein-Barr Virus Infections ; pathology ; Female ; Herpesvirus 4, Human ; Humans ; Intensive Care Units, Pediatric ; Killer Cells, Natural ; Lung Injury ; virology ; Lymphohistiocytosis, Hemophagocytic ; pathology ; virology ; Male ; Pulmonary Fibrosis ; pathology ; virology ; Retrospective Studies ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEwe aimed to investigate the mutation and expression of BRAF gene in mature T/NK cell lymphoma tissues and cell lines, explore the correlation between gene alterations and clinicopathological features and clinical outcomes of mature T/NK cell lymphoma.

METHODSFirstly, we detected common mutant sites of BRAF (locus 1 799 mutation in exon 15 and loci 463, 465 and 468 mutation in exon 11) in lymphoma Jurkat, Hut-78 and YTS cell lines, normal peripheral blood lymphocytes, different types of mature T/NK cell lymphoma and reactive hyperplasia lymph nodes by direct sequencing. Then we measured the expression of BRAF in Jurkat, Hut-78, YTS cells and normal peripheral blood lymphocytes by real time-PCR and Western-blot detection. We also used immunohistochemistry (IHC) to detect the expression of BRAF in mature T/NK cell lymphoma tissues and reactive hyperplasia lymph nodes, and to analyze the correlation between the expression of BRAF and clinocopathological features and clinical outcomes.

RESULTSWe did not find common BRAF mutation in mature T/NK cell lymphoma tissues and cell lines, and the relatively expression of BRAF gene mRNA in normal peripheral blood lymphocytes, YTS, Hut-78 and Jurkat cells were 1.000, 5.207±0.013, 8.412±0.615 and 36.720±1.797, respectively, and protein expressions were 0.051±0.003, 0.102±0.013, 0.113±0.017 and 0.304±0.010, respectively, and the expression of BRAF in peripheral T cell lymphoma Jurkat cells was significantly higher than that of Hut-78, YTS cells and normal lymphocytes (P<0.05). Only 6 of 58 peripheral T cell lymphomas (10.3%) had positive BRAF expression, and were the subgroups of peripheral T cell lymphoma-unspecified type. The statistical data did not show any correlation between positive expression of BRAF and gender, age, clinical stage, location, lactate dehydrogenase in the 21 cases of peripheral T cell lymphoma-unspecified type (P<0.05), but the positive rate of BRAF in the effective treatment group (8.3%) was significantly lower than that of the invalid group (55.6%, P<0.05).

CONCLUSIONThe expression of BRAF gene may become a marker of malignant biological characteristics and clinical therapeutic target of peripheral T cell lymphoma.

Exons ; Humans ; Immunohistochemistry ; Killer Cells, Natural ; Lymphoma, T-Cell, Peripheral ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Pseudolymphoma ; genetics ; metabolism ; RNA, Messenger ; metabolism