Collapsing Glomerulopathy (CG) is a rare entity presenting as nephrotic syndrome and rapidly progressive renal deterioration. It has been first identified among African-American patients and subsequently dubbed HIV-associated nephropathy after a number of patients with HIV were found to have CG. It has re-emerged recently among patients with COVID-19. To our knowledge, this is the first case of primary collapsing glomerulopathy in the country to be published. The case is a 36-year-old Filipino female admitted due to bipedal edema which started 2 weeks post-partum. She has no comorbidities and social history was negative for illicit drug use. Initial work up showed hypoalbuminemia and diffuse hepatic disease on ultrasound. She was referred to a gastroenterologist where albumin infusion and paracentesis was done but with no improvement. She developed anasarca and was admitted. Paracentesis obtained minimal ascitic fluid. Serum ascites albumin gradient was low and baseline laboratories showed high creatinine, hypoalbuminemia, and albuminuria. 24-hour urine protein was 11 grams, ANA and anti-DsDNA were negative and c3 and c4 levels were normal. Hepatitis profile was negative for infection. Abdominal CT scan revealed multiple hypoenhancing lesions. Tumor markers CA-125, CA 19-9 and CA 15-3 were high. Breast ultrasound showed simple breast cyst. Gynecology consult was called where pap smear was negative for atypical cells. Surgery service recommended monitoring for the pancreatic and breast lesions. Kidney biopsy was delayed due to new onset bacterial pneumonia. COVID-19 RT-PCR test was negative. Patient was discharged improved with no edema. On follow up, the kidney biopsy result came out to be collapsing glomerulopathy. HIV test was then done and was negative. Bipedal edema and albuminuria recurred. She was started on tacrolimus. She has been on regular follow up and currently has no edema, no proteinuria and normal creatinine level. This is an interesting case as the primary glomerular disease has been masked by the earlier laboratory findings which led us to think of liver disease then a paraneoplastic nephrotic syndrome. Ultimately, the renal biopsy revealed the diagnosis. This serves as an index case for primary collapsing glomerulopathy in a Filipino patient on remission after being treated with tacrolimus.
Nephrotic Syndrome ; Immunosuppression Therapy

In the tumor microenvironment, metabolic reprogramming can impact metabolic characteristics of T cells, thus inducing immunosuppression to promote tumor immune escape. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in regulating diverse functions of various immune cells. This review mainly focuses on the molecular mechanism of mTOR signaling in regulating cellular energy metabolism process, and the activation status of mTOR signaling under different nutritional environments. In addition, it also summarizes the role of the mTOR signaling in regulatory T cell (Tregs) metabolism and function in current studies, and evaluates the potential of mTOR as a clinical immunotherapeutic target and its current application challenges.
Immunosuppression Therapy ; Metabolic Reprogramming ; Signal Transduction ; Sirolimus ; T-Lymphocytes, Regulatory ; TOR Serine-Threonine Kinases ; Humans

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

We present a case of Nannizziopsis spp infection in an immunocompromised patient, describe clinical findings, investigation results and treatment. This rare fungal infection is reported in reptiles and humans, but not other mammals. There are only twenty case reports in medical literature to date, most in immunocompromised patients.

A 64-year-old kidney transplant recipient from urban Nigeria presented with a verrucous plaque on his dorsal left hand which has grown rapidly over the two months. He was concerned that it might represent cancer. On further examination he also had a subcutaneous fluctuant masses on his left flank and left upper arm, a fleshy mucosal plaque and a large tender fluctuant swelling over his right tibia. He was clinically well, but in the preceding months he reported haemoptysis and 7 kilograms weight loss.

Skin biopsies from multiple sites showed identical features: suppurative granulomatous inflammation and elongated elements consistent with fungal hyphae. Grocott special staining showed scattered fungal hyphae. Beta-D-glucan was raised at 441.4 pg/mL [3-6 pg/mL]. Subsequent molecular identification confirmed Nanniziopsis spp, likely to be N. guarroi. He was treated with intravenous amphotericin-B for 7 weeks and was then switched to oral posaconazole for one month with complete resolution.

Nannizziopsis is an emerging human pathogenic fungus that predominantly causes disease in immunocompromised individuals. This case highlights the importance of suspecting atypical fungal infection in immunocompromised individuals presenting with polymorphic skin lesions and the critical diagnostic role of skin biopsy and culture.

Objectives Objectives To investigate how the imbalance of innate lymphoid cells (ILCs)in the peripheral blood of patients with lung adenocarcinoma affects the balance of downstream mononuclear macrophages and T helper (Th) cells, and to identify the impact of the imbalance of ILCs on the immune status and prognosis of lung adenocarcinoma. Methods The peripheral blood of 20 patients with lung adenocarcinoma and normal controls were collected. The percentage of ILCs, mononuclear macrophages and T lymphocyte in peripheral blood were analyzed by flow cytometry. The characteristic cytokine secretion levels of various types of immune cells in peripheral blood were detected by real-time fluorescence quantitative PCR. Results Compared with the normal controls, the proportion of M2 mononuclear macrophages, ILC1 and ILC2 in patients with lung adenocarcinoma was up-regulated, while the proportion of M1 mononuclear macrophages, CD4⁺ T and CD8⁺ T was down-regulated. The mRNA expression of related cytokines of M1 mononuclear macrophages and ILC1 were decreased; while the mRNA expression of related cytokines of M2 mononuclear macrophages and ILC2 were increased. Along with the decreased CD4⁺T cells-associated cytokine T-bet mRNA expression, and the increased GATA3 mRNA expression. Moreover, the expression of PD-1 in CD8⁺ T cells was also up-regulated. Conclusion The imbalance of ILCs in peripheral blood of patients with lung adenocarcinoma promotes the imbalance of mononuclear macrophages and Th cells, which altogether maintains the immunosuppression in patients with lung adenocarcinoma, and promotes the development of lung adenocarcinoma.
Humans ; Lymphocytes ; Immunity, Innate ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Adenocarcinoma of Lung ; Immunosuppression Therapy ; RNA, Messenger

A complex pathophysiological mechanism is involved in brain injury following cerebral infarction. The neurovascular unit (NVU) is a complex multi-cellular structure consisting of neurons, endothelial cells, pericyte, astrocyte, microglia and extracellular matrix, etc. The dyshomeostasis of NVU directly participates in the regulation of inflammatory immune process. The components of NVU promote inflammatory overreaction and synergize with the overactivation of autonomic nervous system to initiate stroke-induced immunodepression (SIID). SIID can alleviate the damage caused by inflammation, however, it also makes stroke patients more susceptible to infection, leading to systemic damage. This article reviews the mechanism of SIID and the roles of NVU in SIID, to provide a perspective for reperfusion, prognosis and immunomodulatory therapy of cerebral infarction.
Humans ; Endothelial Cells ; Stroke ; Neurons/physiology* ; Immunosuppression Therapy/adverse effects* ; Cerebral Infarction

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.
Humans ; Multiple Myeloma/pathology* ; T-Lymphocytes, Regulatory/pathology* ; Immune Tolerance ; Plasma Cells/pathology* ; Immunosuppression Therapy ; Tumor Microenvironment

OBJECTIVE: To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA). METHODS: The clinical data of 76 patients with treatment-naive TD-NSAA in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from December 2017 to June 2021 were retrospectively analyzed. Among them, 45 cases were treated with eltrombopag combined with CsA, and 31 patients with compatible baseline characters were treated with CsA alone. The efficacy of patients between the two groups was compared, and the factors affecting the curative effects were also analyzed. RESULTS: There were significant differences in hematological response (HR) and complete response(CR) rates between the two groups at 3, 6, 12 months, and follow-up endpoint of treatment (P<0.05). With the prolongation of eltrombopag treatment time, the curative effect increased gradually, and the patients achieved more CR and HR rates by the end of the follow-up period. Simultaneously, with the increase in the maximum stable dose of eltrombopag, the HR rate increased gradually. The megakaryocyte count in eltrombopag group was higher than that in control at 6 and 12 months (P<0.05). Compared with the control group, the median time of platelet transfusion independence in eltrombopag group was more shorter (P=0.018), and the median platelets transfusion volume was lower (P=0.009). At 3, 6, 12 months after eltrombopag, the change of platelet in eltrombopag group was higher than that in the control group (P<0.05). Analysis of related factors affecting the efficacy showed that sex, age, iron overload, platelet count before treatment had no effect on the efficacy, and the median maximum stable dosage and the administration period for eltrombopag were related to the curative effect. The patients of eltrombopag group experienced adverse events of varying degrees, but the reactions were mild and mostly tolerated. CONCLUSION Eltrombopag can effectively improve the hematopoietic response and promote platelet recovery for TD-NSAA patients with relatively more residual hematopoietic cells, and it is safe and well tolerated.
Humans ; Anemia, Aplastic/therapy* ; Retrospective Studies ; Treatment Outcome ; Cyclosporine/therapeutic use* ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use*

Humans ; SARS-CoV-2 ; COVID-19 ; Reverse Transcriptase Polymerase Chain Reaction ; Immunosuppression Therapy ; COVID-19 Testing

OBJECTIVE: To observe the effects of herbal cake separated moxibustion on macrophage effector molecule T-cell immunoglobulin and mucin-domain containing-4 (Tim-4) and ubiquitination of programmed cell death protein 1 (PD-1) in rabbits with immunosuppression, and to explore the possible mechanism on herbal cake separated moxibustion in improving immunosuppression. METHODS: Thirty-two big-ear white rabbits were randomly divided into a normal group, a model group, a moxa stick moxibustion group and a herbal cake separated moxibustion group, 8 rabbits in each group. Except the normal group, the immunosuppression model was established by intraperitoneal injection of cyclophosphamide of60 mg/kg in the other 3 groups. "Shenque" (CV 8), "Shenshu" (BL 23), "Zusanli" (ST 36), etc. were selected in both the moxa stick moxibustion group and the herbal cake separated moxibustion group. Moxa stick moxibustion was applied in the moxa stick moxibustion group, one cone at each acupoint; herbal cake separated moxibustion was applied in the herbal cake separated moxibustion group, 5 cones at each acupoint. The intervention was given once every other day for 10 times in both groups. Leukocyte content in peripheral blood was detected by blood cell analyzer; the positive expression of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood was measured by flow cytometry, the serum levels of interleukin 2 (IL-2), CD₈, CD₆₈ and Tim-4 were detected by ELISA, and the expression of Tim-4 and F-box only protein 38 (FBXO38) in the liver and spleen tissues was measured by immunohistochemistry. RESULTS: Compared with the normal group, in the model group, white blood cell count (WBC) and percentage of neutrophils (NEU%) were decreased while percentage of lymphocyte (LYM%) was increased (P<0.01) in peripheral blood; the positive expression rates of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood were increased (P<0.01); the serum levels of IL-2, CD₆₈ and Tim-4 were increased (P<0.01), the serum level of CD₈ was decreased (P<0.01); the average optical density (AOD) of Tim-4 in the liver tissue and FBXO38 in the liver and spleen tissues was increased (P<0.01). Compared with the model group, in the moxa stick moxibustion group and the herbal cake separated moxibustion group, WBC and NEU% were increased (P<0.01); the positive expression rates of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood were decreased (P<0.01); the serum levels of IL-2, CD₆₈ and Tim-4 were decreased (P<0.01), the serum levels of CD₈ were increased (P<0.01); the AOD of Tim-4 and FBXO38 in the liver tissue and FBXO38 in the spleen tissue was decreased (P<0.01, P<0.05). Compared with the moxa stick moxibustion group, in the herbal cake separated moxibustion group, the positive expression rate of PD-1 in CD⁺₆₈ macrophages in peripheral blood was increased (P<0.05); serum level of Tim-4 was increased (P<0.01); AOD of Tim-4 in the liver tissue was decreased (P<0.05). CONCLUSION Herbal cake separated moxibustion can improve immunosuppression by regulating the expression of macrophage effector molecule Tim-4 and the FBXO38 mediated ubiquitination of PD-1, Tim-4 may be one of the specific indexes of immunomodulation involving with herbal cake separated moxibustion.
Animals ; Rabbits ; Interleukin-2/genetics* ; Moxibustion ; Programmed Cell Death 1 Receptor/genetics* ; Immunosuppression Therapy ; Ubiquitination