Monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma: an autopsy case and review of the literature.

A 67-year-old man underwent renal transplantation in his twenties. He developed refractory pleural effusion, with many large lymphocytes with severe atypia and mitosis in the effusion, indicating malignant lymphoma. He finally died of respiratory failure. An autopsy revealed atypical lymphocytes positive for CD3, CD4, and CD30 and negative for CD8, CD20, PAX5, human herpesvirus (HHV) 8, and Epstein-Barr virus-encoded small RNAs by immunohistochemistry and in situ hybridization. Atypical lymphocytes also had T-cell receptor gene rearrangements Jß2, Jγ2, and Jδ1 and chromosomal aberrations der(8)t(1;8)(q21;p21), add(13)(q12), add(14)(q32), and add(16)(q12-13). A few atypical lymphocytes were present at other sites. We finally diagnosed this case as monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma. A literature review only identified six cases (four HHV8-negative, two HHV8-positive) of effusion lymphoma of T-cell type, including the present case. Interestingly, about half of HHV8-negative and HHV8-positive cases had a history of renal transplantation in their twenties. All cases showed tumor CD30 expression, whereas CD4 and CD8 expressions were inconsistent. These findings indicated that this lymphoma may be associated with post-transplant lymphoproliferative disorder by renal transplantation at a young age, although further cases need to be analyzed.

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis.

Objective: Th1 and Th2 cells and their associated cytokines function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact roles are uncertain. We performed a meta-analysis to examine the relationship of these cells and cytokines with SLE. Methods: Multiple databases were searched to identify publications that reported the percentages of Th1 and Th2 cells and their associated cytokines in SLE patients and healthy controls (HCs). Meta-analysis was performed using Stata MP version 16. Results: SLE patients had a lower percentage of Th1 cells, a higher percentage of Th2 cells, and higher levels of Th1- and Th2-associated cytokines than HCs. SLE treatments normalized some but not all of these indicators. For studies in which the proportion of females was less than 94%, the percentage of Th2 cells and the level of IL-10 were higher in patients than HCs. SLE patients who had abnormal kidney function and were younger than 30 years old had a higher proportion of Th1 cells than HCs. SLE patients more than 30 years old had a higher level of IL-6 than HCs. Conclusion: Medications appeared to restore the balance of Th1 cells and other disease indicators in patients with SLE. Gender and age affected the levels of Th1 and Th2 cells, and the abnormally elevated levels of Th2 cells appear to be more pronounced in older patients and males. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296540].

Food allergy testing in atopic dermatitis.

Food allergy and food-related worsening of dermatitis can occur in patients with atopic dermatitis (AD). We reviewed the relationship of AD with food allergen hypersensitivity and the risks and benefits of food allergen testing and avoidance in patients with AD. Skin prick testing and specific immunoglobulin E to aeroallergens may identify patients with immediate hypersensitivity. Atopy patch tests may detect non-immunoglobulin E-mediated reactions but are not standardized or routinely used. Younger children with more severe AD in whom the optimal management failed may have food-triggered AD. Egg, milk, and peanut account for most food allergens. Elimination of relevant food allergens should improve AD but must be guided by appropriate allergy testing and establishing clinical relevance. Serum immunoglobulin E panels for food allergens are discouraged in the primary care setting because of their difficulty of interpretation. Empiric avoidance of foods is entirely discouraged in AD because of their risk of causing nutritional issues, food allergy, and other problems.

The potential role of follicular helper T cells and helper T cells type 1 in Warthin tumour.

Warthin tumour (WT) is a benign tumour of the salivary gland that proliferates in both glandular epithelial and lymphoid tissue components, and rarely exhibits cystic changes. T follicular helper cells (Tfh) are involved in the formation and maintenance of germinal centres, the differentiation of B cells into plasma cells, and the maintenance of helper T cell type 2 (Th2)-dominant humoral immune responses. T-bet induces differentiation into helper T cell type 1 (Th1) by suppressing differentiation into Tfh and enhances cellular immune responses. The objective of this study was to enhance our understanding of the immune responses and relationship between Tfh and Th1 cells in patients with WTs. In this study, we classified WTs (n = 64) into solid-type (n = 25) and cyst-type (n = 39). We also performed immunostaining of the Tfh markers CXCR5 and CD40 L, and the Th1 marker T-bet for statistical analysis. The cyst-type exhibited significant atrophy of the germinal centre area (P = 0.0019), significantly fewer Tfh-positive lymphocytes in germinal centres (P < 0.0001), and significantly more T-bet-positive lymphocytes in the epithelium (P = 0.0017). We observed that Tfh were involved in the formation and maintenance of lymphoid follicles in WTs. In the cyst-type, Th2-dominant humoral immune responses were suppressed, and Th1-dominant cellular immune responses may have caused damage to tumour tissue.

Interleukin-27 inhibits helper T cell type-2 response in allergic rhinitis.

OBJECTIVE: Interleukin-27 (IL-27) is a recently identified cytokine which plays both pro-inflammatory and anti-inflammatory effect in different diseases. However, its function in the pathogenesis of allergic rhinitis (AR) was not clear so far. METHODS: Quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) were performed to detect the expression of interleukin 27 (IL-27) and Th2 cytokines (IL-4, IL-5, IL-13) from 22 patients diagnosed with AR and 20 normal controls. Purified peripheral blood mononuclear cells (PBMCs) were prepared for in vitro experiment. RESULTS: Serum mRNA and protein levels of IL-27 were down-regulated in AR patients compared with normal controls. The expression of IL-27 showed negative correlation with Th2 cytokines. In vitro study showed that IL-27 significantly inhibited Th2 cytokines expression from PBMCs. CONCLUSION: Our results suggested that decreased IL-27 expression in AR were correlated with Th2 response. IL-27 may be used as potential target in the future treatment of AR.

[Blast-like tumor tissue in cervical lymph node with expression of placental alkaline phosphatase]. / Blastäres Tumorgewebe in Halslymphknoten mit Expression plazentaalkalischer Phosphatase.

We report a case of ALK1-positive anaplastic large cell lymphoma with expression of placental alkaline phosphatase (PLAP) in many tumor cells. Initially, due to the positivity of tumor cells for CD30 and PLAP, lymph node metastasis of a germ cell neoplasm was discussed. Anaplastic large cell lymphomas of T­cell lineage form a group of rare non-Hodgkin lymphomas with heterogeneous morphological and immunohistochemical appearance. They may imitate other neoplasms, such as large cell B­cell lymphomas, metastasis of a carcinoma, melanoma, embryonal carcinoma or seminoma, rhabdomyosarcoma and inflammatory myofibroblastic tumor. Only an extended immunohistochemistry panel leads to an accurate diagnosis.

Adaptive Immunity to Cryptococcus neoformans Infections.

The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of fungal pathogens with different phenotypic and genotypic diversity that cause disease in immunocompromised patients as well as in healthy individuals. The immune response resulting from the interaction between Cryptococcus and the host immune system is a key determinant of the disease outcome. The species C. neoformans causes the majority of human infections, and therefore almost all immunological studies focused on C. neoformans infections. Thus, this review presents current understanding on the role of adaptive immunity during C. neoformans infections both in humans and in animal models of disease.

Hodgkin lymphoma as a novel presentation of familial DICER1 syndrome.

UNLABELLED: DICER1 germline mutations are associated with an inherited cancer syndrome, most commonly presenting with pleuropulmonary blastoma (PPB), ovarian sex cord tumors, thyroid cysts/goitre, and cystic nephroma. We describe the occurrence of a Hodgkin lymphoma (HL) of the T cell phenotype in a family with DICER1 syndrome. The patient presented with PPB Type I and HL. Immunohistochemical staining of the Hodgkin and Reed-Sternberg cells revealed CD30, TGP, CD2, CD3, CD15, and IRF4 positivity and weekly positivity of PAX5. T cell receptor repertoire analysis suggested HL of T cell origin, which is in contrast to common B cell-derived HL. The mother had been diagnosed with thyroid cysts, one sister had died from a primitive neuroectodermal tumor, and a brother had died from PPB Type III. Two mutational events were revealed in all affected family members; a single bp deletion, c.5299delC, leading to a frameshift and premature stop in exon 24 and a heterozygous variant (c.4616C>T; p.Thr1539Met) located in exon 23 of the DICER1 gene. This variant is predicted to be benign by in silico analysis. CONCLUSION: Future studies looking for DICER1 mutations in HL cases of the T cell phenotype will be important to confirm its association with constitutional DICER1 syndrome. WHAT IS KNOWN: • DICER1 germline mutations are associated with an inherited cancer syndrome, most commonly pleuropulmonary blastoma, ovarian sex cord tumors, thyroid cysts/goitre, and cystic nephroma. • Hodgkin lymphoma is one of the most frequent types of malignant lymphomas and typically arises sporadically. T cell-derived Hodgkin lymphomas are exceptionally rare. What is New: • DICER1 syndrome may have an even broader phenotypic spectrum and seems to be associated with rare forms of T cell Hodgkin lymphoma.

Stereotactic radiosurgery and immunotherapy for metastatic spinal melanoma.

The management of metastatic spinal melanoma involves maximizing local control, preventing recurrence, and minimizing treatment-associated toxicity and spinal cord damage. Additionally, therapeutic measures should promote mechanical stability, facilitate rehabilitation, and promote quality of life. These objectives prove difficult to achieve given melanoma's elusive nature, radioresistant and chemoresistant histology, vascular character, and tendency for rapid and early metastasis. Different therapeutic modalities exist for metastatic spinal melanoma treatment, including resection (definitive, debulking, or stabilization procedures), stereotactic radiosurgery, and immunotherapeutic techniques, but no single treatment modality has proven fully effective. The authors present a conceptual overview and critique of these techniques, assessing their effectiveness, separately and combined, in the treatment of metastatic spinal melanoma. They provide an up-to-date guide for multidisciplinary treatment strategies. Protocols that incorporate specific, goal-defined surgery, immunotherapy, and stereotactic radiosurgery would be beneficial in efforts to maximize local control and minimize toxicity.

1, 25 (OH)2-Vitamin-D3 attenuates Th17-related cytokines expression in peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis / 中华内科杂志

Objective To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25 (OH) 2D3] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA).Methods Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected.The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)2D3 and methotrexate (MTX).After co-culture,the serum levels of Th17 cytokines interleukin (IL)-17,IL-6,tumour necrosis factor alpha (TNFα) were analyzed by cytometric bead array (CBA).The level of IL-22 was analyzed by enzyme-linked immunosorbent assay (ELISA).The independent samples t test and one-way analysis of variance (ANOVA) were used for statistical analysis.Results The levels of cytokines IL-17,TNFα,IL-6 and IL-22 in RA group were significantly higher than those in the control group[(43 ± 6) ng/L,(5.91 ± 2.53) ng/L,(16.6 ± 12.0) ng/L,(51 ± 17) ng/L vs (21 ±3)ng/L,(2.63 ±0.27) ng/L,(4.2 ±2.3) ng/L,(22 ± 14) ng/L].Each of the three different 1,25 (OH) 2 D3 doses inhibited secretion of IL-17 [(533 ± 47) pg/ml,(426 ± 55) pg/ml,(319 ± 86) pg/ml],TNFα[(424 ± 82) pg/ml,(382 ± 79) pg/ml,(326 ± 87) pg/ml],and IL-6 [(5 513 ± 3 429) pg/ml,(4 555 ±3 157)pg/ml,(3 748 ± 1 919)pg/ml]in RA group (P ＜0.05),yet no statistical difference was found in IL-22 secretion with a trend of decrease after treatment of 1,25 (OH)2D3.Three different doses of MTX inhibited secretion of IL-17 [(452 ± 50) pg/ml,(372 ± 67) pg/ml,(315 ± 104) pg/ml] and TNFα [(319 ± 74) pg/ml,(292 ± 59) pg/ml,(266 ± 64) pg/ml] in RA group (P ＜ 0.05).However,levels of IL-6 and IL-22 were not affected after treated with MTX.Conclusion Our data indicated that 1,25 (OH)2D3 may play as an immune modulating agent to suppress Th17 cell cytokines.Supplement of vitamin D has the effective potential to treat patients with RA or other Th17 cell mediated autoimmune disorders.

Remission of food allergy by the Janus kinase inhibitor ruxolitinib in mice.

To clarify the role of Janus kinase (JAK) in and the efficacy of JAK inhibitors on food allergy, we investigated the effect of the clinically available JAK inhibitor ruxolitinib on mouse food allergy and the functions of cultured mast cells in vitro. Anaphylactic symptoms including diarrhea and decreases in body temperature pursuant to oral ovalbumin (OVA) challenges in food allergy mice were attenuated by the daily oral administration of ruxolitinib. This drug inhibited increases in mouse mast cell protease-1 concentrations in the serum and mast cell numbers in the intestines of these mice as well as degranulation, IL-13 production, and the spontaneous and IL-9-dependent survival of mouse bone marrow-derived mast cells in spite of the absence of an effect of ruxolitinib on passive systemic anaphylaxis. Anti-OVA IgG2a, IgE, and IgG1 serum levels and the release of IFN-γ, IL-4, IL-9, and IL-10 from the OVA-restimulated splenocytes of food allergy mice were also decreased by the treatment. Moreover, ruxolitinib administration to mice that had already exhibited anaphylactic responses to previous challenges reduced anaphylactic responses to further oral OVA challenges, which suggested that ruxolitinib has a therapeutic potential on food allergy. Our results showed that ruxolitinib remitted food allergy in mice mainly through immunosuppression and the prevention of mast cell hyperplasia, and partially through the inhibition of mast cell activation. We consider JAK inhibition to be a promising strategy for the prevention of food allergy, and ruxolitinib along with its derivatives inhibiting JAK as good candidates for therapeutic drugs to treat food allergy.