Immune checkpoint inhibitors have progressed rapidly over the past decade and have become one of the most promising oncology treatments. However, immune checkpoint inhibitors reduce T-cell tolerance and lead to a unique spectrum of immune-related adverse events (IRAE). IRAE can involve multiple systems, including endocrine, gastrointestinal, respiratory and skin systems and there is no predictive marker with high specificity and sensitivity. Mild IRAE can be alleviated by discontinuing immune checkpoint inhibitors while severe IRAEs require active intervention. The first-line treatment is glucocorticoids, and immunosuppressants can be considered in refractory cases. However the optimal choice of immunosuppressants is currently controversial. This review provides an overview of the epidemiology and possible mechanisms of immune-related adverse events, outlines some promising predictive biomarkers, and describes several immunotherapy-related organ toxicity and management.
Humans ; Immunologic Factors/adverse effects* ; Immunosuppressive Agents ; Immunotherapy/adverse effects*

A prospective study was carried out on 31 healthy individuals and 32 patients with rheumatoid arthritis at the Military Hospital N0 103 and the Enterology Department of the Police Hospital N0 198. The results showed that: in the patient group, there were increases of number of white blood cells, and lymphocytes, as compared to the control group (p<0.001); there was also wide fluctuation of tumor necrosis factor (TNF-), from 22.41 pg/ml to 1341.62pg/ml. 75% patients had concentration of rheumatoid factor RF≥8 IU/ml (positive). There were agreeable correlations between the number of lymphocytes T, Ta with lymphocytes B at rate r=0.64 (p<0.05); between the number and percentage of Ta-cell with serum concentration of rheumatoid factor (RF) in the patients at low level of r=0.24 and r=0.33
Arthritis, Rheumatoid, Immunologic Factors

BACKGROUND: This study examined the outcomes of ABO incompatible living donor liver transplantation (LDLT). The changes in the immunologic factors that might help predict the long term outcomes were also studied. METHODS: Twenty-three patients, who underwent ABO incompatible LDLT from 2010 to 2015, were reviewed retrospectively. The protocol was the same as for ABO compatible LDLT except for the administration of rituximab and plasma exchange. The clinical outcomes and immunologic factors, such as isoagglutinin titer and cluster of differentiation 20+ (CD20+) lymphocyte levels were reviewed. RESULTS: The center showed a 3-year survival of 64% with no case of antibody-mediated rejection. When transplantation-unrelated mortalities (for example, traffic accidents and myocardial infarction) were removed from statistical analysis, the 3-year survival was 77.8%. Although isoagglutinin titers continued to remain at low levels, the CD20+ lymphocyte levels recovered to the pre-Rituximab levels at postoperative one year. CONCLUSIONS: As donor shortages continue, ABO incompatible liver transplantation is a feasible method to expand the donor pool. On the other hand, caution is still needed until more long-term outcomes are reported. Because CD20+ lymphocytes are recovered with time, more immunologic studies will be needed in the future.
ABO Blood-Group System ; Accidents, Traffic ; B-Lymphocytes ; Hand ; Hemagglutinins ; Humans ; Immunologic Factors ; Liver Transplantation* ; Liver* ; Living Donors* ; Lymphocytes ; Methods ; Mortality ; Plasma Exchange ; Retrospective Studies ; Rituximab ; Tissue Donors

To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3.
 Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes.
 Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05).
 Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.
Adjuvants, Immunologic ; pharmacology ; Aminoquinolines ; pharmacology ; Animals ; Case-Control Studies ; Female ; Forkhead Transcription Factors ; metabolism ; Humans ; Imiquimod ; Immunosuppressive Agents ; administration & dosage ; pharmacology ; Lymphocyte Count ; Methotrexate ; administration & dosage ; pharmacology ; Mice ; Mice, Inbred BALB C ; Psoriasis ; drug therapy ; immunology ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Random Allocation ; Spleen ; cytology ; T-Lymphocytes, Regulatory ; cytology ; drug effects ; metabolism

Proteinuria is a characteristic finding in glomerular diseases and is closely associated with renal outcomes. In addition, therapeutic interventions that reduce proteinuria improve renal prognosis. Accumulating evidence has demonstrated that podocytes act as key modulators of glomerular injury and proteinuria. The podocyte, or glomerular visceral epithelial cell, is a highly specialized and differentiated cell that forms interdigitated foot processes with neighboring podocytes, which are bridged together by an extracellular structure known as the "slit diaphragm" (SD). The SD acts as a size- and charge-selective barrier to plasma protein. Derangement of SD structure or loss of SD-associated protein results in podocyte injury and proteinuria. During the past decades, several immune-modulating agents have been used for the treatment of glomerular diseases and for the reduction of proteinuria. Interestingly, recent studies have demonstrated that immunosuppressive agents can have a direct effect on the SD-associated proteins and stabilize actin cytoskeleton in podocyte and have therefore introduced the concept of nonimmunologic mechanism of renoprotection by immunomodulators. This review focuses on the evidence that immuno-modulating agents directly target podocytes.
Actin Cytoskeleton ; Epithelial Cells ; Foot ; Immunologic Factors ; Immunomodulation ; Immunosuppressive Agents* ; Nephrotic Syndrome ; Plasma ; Podocytes* ; Prognosis ; Proteinuria

The nature of immunoresponse is to protect of body from antigens, but excessive immunoresponse leads harmful and serious effects for body. The communosuppressive drugs were effective in the treatment of patients with renal transplantation, primary nephritic syndrome and pyelonephritis. However, the drugs cause many side and adverse effects such as infection. It should monitor clinical manifestations and examine periodical blood during the treatment to reduce the dose or interruption of the treatment.
Suppressor Factors, Immunologic ; Kidney Transplantation

20 patients with glomerular nephritis received a biopsy through the skin to study the histological lesion by photomicroscopy and the direct fluorescent immune including the electromicroscopic immune and super structure for some cases. Some lesion were classified by the photomicroscopy comprise the minimal lesion glomerular disease (46%), the glomerular nephritis with intervascular proliferation (35%); glomerular nephritis with membrane proliferation with reduction or increase of crescent cells (15%). The results of comparison of the photomicroscope with the direct fluorescent immune found 1 patient with the glomerular nephritis IgA. In addition to, there is a deposition of IgG, IgM and IgA accompanied with C19 and/or C3c in the basal membrane of the glomerular and membrane Bowman. These showed that pathology of glomerular has an immunopathological mechanism. The deposition of the immunological complexes in the glomerular helped the prognosis of the clinical correspond of old patients to the treatment
Immunologic Factors ; adult ; Nephrotic Syndrome

PURPOSE: To compare the short term effects of topical 0.05% cyclosporine (CsA) and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate (CS-HA) on dry eye ocular surfaces. METHODS: 36 patients with moderate to severe dry eye (5 mm/5 min or less with Schirmer's test or tear break up time (BUT) less than 6 seconds), were treated with topical application of CS-HA on one eye and CsA on the other 4 times a day for 6-8 weeks. BUT, Schirmer's test without anesthesia, and conjunctival impression cytology (CIC; goblet cell density, nucleus to cytoplasmic ratio, and epithelial cell morphology) were evaluated and compared between eyes before and after treatment (repeated measurement of ANOVA). RESULTS: After treatment, BUT and tear wettings were significantly prolonged in each group. Topical CsA treated eyes had greater increase in BUT (p=0.026); there was no significant difference in tear wetting (p=0.132). While the 3 parameters of CIC improved in both groups, goblet cell density was significantly higher in eyes treated with CsA (p=0.033). CONCLUSIONS: While both CS-HA and 0.05% CsA eyedrops improve ocular surfaces, topical CsA may have a better effect on enhancing tear film stability and goblet cell density.
Adjuvants, Immunologic/administration & dosage ; Administration, Topical ; Cell Count ; Chondroitin Sulfates/*administration & dosage ; Conjunctiva/drug effects/pathology ; Cyclosporine/*administration & dosage ; Drug Administration Schedule ; Drug Combinations ; Drug Therapy, Combination ; Dry Eye Syndromes/*drug therapy/metabolism/pathology ; Epithelium/drug effects/pathology ; Female ; Follow-Up Studies ; Goblet Cells/drug effects/pathology ; Humans ; Hyaluronic Acid/*administration & dosage ; Immunosuppressive Agents/*administration & dosage ; Male ; Middle Aged ; Ophthalmic Solutions/administration & dosage ; Tears/drug effects/metabolism ; Time Factors ; Treatment Outcome

OBJECTIVETo investigate the immunomodulatory effects of Fomes fomentarius polysaccharides (FFP) in mice.

METHODSMTT assay was employed to evaluate the in vitro metabolic activity of the mouse splenocytes treated with FFP at different concentrations, and the secretion of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma) and interleukin 2 (IL-2) from the cells were measured by enzyme-linked immunosorbent assay. The changes in the phagocytotic activity of mouse macrophage in response to FFP treatment were evaluated by phagocytosis percentage of chicken red blood cells (CRBCs). The effect of FFP on the humoral immunity was assessed in mice immunized with sheep red blood cells (SRBCs) by measuring the serum levels of specific antibody (hemolysin) against SRBCs.

RESULTSFFP at the concentrations of 25, 50, and 100 microg/ml all significantly enhanced the metabolic activity of mouse splenocytes in vitro and increased the production of TNF-alpha, IFN-gamma and IL-2. FFP treatment also markedly enhanced the metabolic activity of mouse peritoneal exudate cells and TNF-alpha production by the cells. At the doses of 25, 50, and 100 mg/kg, FFP significantly increased serum hemolysin level in mice immunized with SRBCs, and FFP at 50 and 100 mg/kg obviously increased the capacity of mouse peritoneal macrophages in vivo for CRBC phagocytosis.

CONCLUSIONFFP can promote the secretion of TNF-alpha, IFN-gamma and IL-2 by mouse immunocytes and enhance mouse humoral immune response and the phagocytotic activity of the macrophages.

Adjuvants, Immunologic ; pharmacology ; Animals ; Coriolaceae ; chemistry ; Female ; Immunologic Factors ; immunology ; pharmacology ; Interferon-gamma ; secretion ; Interleukin-2 ; secretion ; Macrophages, Peritoneal ; drug effects ; immunology ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Phagocytosis ; drug effects ; Polysaccharides ; isolation & purification ; pharmacology ; Tumor Necrosis Factor-alpha ; secretion

OBJECTIVETo evaluate the effect of Group A streptococcus preparation (sapylin) combined with cisplatin on the malignant peritoneal effusion in patients with advanced cancer.

METHODSSixty advanced cancer patients with large amount of peritoneal effusion were divided into two groups: sapylin + cisplatin (DDP) group (30 patients) and control group (DDP alone, 30 cases). All the chemotherapeutic agents were injected intraperitoneally through a catheter.

RESULTSIn sapylin + cisplatin(DDP) group, 11 (36.7%) patients showed CR and 16 (53.3%) PR. The overall response rate (CR + PR) was 90.0%. Those of DDP alone group were 16.7% and 46.7%, the overall response rate was 63.3%. The main adverse effects were fever, nausea, and vomiting.

CONCLUSIONCombined Group A streptococcus preparation (sapylin) and cisplatin is more effective than cisplatin alone for the malignant peritoneal effusion in patients with advanced cancer, and the adverse effects are tolerable.

Adjuvants, Immunologic ; administration & dosage ; Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Ascitic Fluid ; pathology ; Bacterial Proteins ; administration & dosage ; Biological Products ; administration & dosage ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Female ; Humans ; Immunologic Factors ; administration & dosage ; Injections, Intraperitoneal ; Male ; Middle Aged ; Ovarian Neoplasms ; pathology ; therapy ; Peritoneal Neoplasms ; secondary ; therapy ; Stomach Neoplasms ; pathology ; therapy ; Streptococcus pyogenes ; chemistry