Iranian journal of immunology
Volume:17 Issue: 2, Spring 2020

It has been suggested that routine assessment and quantification of different lymphocyte subsets can provide clinically meaningful prognostic information in breast cancer (BC). To determine the relationship between peripheral blood lymphocyte subsets and pathological parameters and response to therapy in patients with BC. Thirty patients with operable breast cancer treated surgically with either modified radical mastectomy or breast conservative surgery, and 20 healthy controls were included. For detection of lymphocyte subsets in peripheral blood; Fluorochrome-labeled monoclonal antibodies were used and cells were analyzed by flow cytometry. Patients were treated with chemotherapy, radiotherapy and hormonal treatment, and followed up to determine relapse and recurrence-free survival (RFS). Significant differences were found in the frequencies of B, T, NK, NKT, and CD28‒T cells between patients with BC and controls. Moreover, a significant difference was found in the percentage of CD8+CD28‒ T cells between patients with different pathologic subtypes of BC and negative correlations were observed between the frequency of CD8+CD28‒T cells and memory B cells, and RFS. Also, a significant difference in the frequency of naïve B cells was found in patients with different tumor grades and a negative correlation was found between the frequencies of B cells and NKT cells. NK, NKT, lymphocytes, and CD28‒ T cells significantly differed between healthy controls and BC patients. Also, memory B cells were associated with good response to treatment while CD28‒ T cells were associated with shorter RFS.

Current evidence indicates the resurgence of whooping cough despite high coverage of whole-cell (wP) and acellular (aP) pertussis vaccines. To investigate the cytokine response to a genetically inactivated protein containing the S1 subunit of pertussis toxin (PTS1) with and without the Listeriolysin O (LLO-PTS1), in comparison with current wP and aP vaccines in the mice model.  Thirty-six female NMRI mice aged 8 to 12 weeks (25 ± 5 g) were divided into six groups, including control (n=6) and five treated groups (n=6/each). Treated groups received intraperitoneal injection of recombinant PTS1, recombinant fusion LLO-PTS1, aP, wP, and sham (phosphate-buffered saline), whereas the control group did not receive anything. After60 days, the serum levels of IFN-γ, IL-4, and IL-17 cytokines were evaluated by ELISA method. Our findings showed LLO-PTS1 significantly increased IL-17 and IL-4 cytokines compared with wP and aP vaccines. IFN-γ failed to increase substantially in the LLO-PTS1 group compared to others, but it was non-inferior to standard vaccines. Our alum free mono-component monovalent recombinant fusion protein (LLO-PTS1) could bear the capacity to stimulate the release of IFN-γ similar to wP and aP vaccines in the mouse model. Besides, it showed better results in stimulating the release of IL-17 and IL-4 response. This study can be regarded as a platform for further probes in booster pertussis vaccine development.

Pseudomonas aeruginosa is considered as the most severe cause of infections in burn patients and pneumonia infections. To study the protective effects of recombinant protein vaccine harboring the PcrV of P. aeruginosa in the mouse model of burn and respiratory infections. Recombinant protein vaccine harboring the PcrV was expressed in the E. coli BL-21 strain. Mice were immunized with the purified recombinant protein, and the antibody titer was measured in the sera obtained from the immunized mice. Immunized and control mice werechallenged by active and passive immunization. The microbial counts in the lung, skin, liver, spleen, and kidney were compared with the control mice. Bioinformatics analysis indicated that the PcrV protein was conserved in 1552 clinical and environmental isolates. Also, the isoelectric point (pI), molecular weight, and Grand Average of Hydropathy (GRAVY) score were analyzed. Mice were injected with recombinant protein, and serum from immunized mice reacted strongly with recombinant antigen at a dilution of 1:64000. The survival rate of mice infected with 5xLD50 of the P. aeruginosa increased significantly up to 75% in the standard strains (PAO1 and PAK), and the number of bacteria, especially in the internal organs (kidney, spleen, and liver) significantly reduced compared to the mice immunized with placebo. Our results demonstrated that the PcrV protein could be an effective candidate vaccine for the generation of antibody response against P. aeruginosa infection.

IL-17 is reported to be associated with the pathophysiology of Orthodontic Tooth Movement (OTM) by affecting osteoclastogenesis.  To explore the changes of Th17 cytokines (IL-17, IL-23, and IL-27) expression and its correlation with receptor activator of nuclear factor kappa B ligand (RANKL) during orthodontic tooth movement.  Thirty patients who needed extraction of the first premolar during orthodontic treatment were included. The gingival crevicular fluid was sampled at the day of application (T0), one hour (T1), 24 hours (T2), one week (T3), four weeks (T4), and 12 weeks (T5) after the application of orthodontic force. The expression of Th17 cytokines and RANKL were measured by using enzyme-linked immunosorbent assay and, their correlations were assessed. The levels of IL-17A, IL-17F, IL-23, and IL-27 at both tension and pressure sides of studied teeth at T2-T4 were significantly higher compared with that of T0 and T1. Moreover, the expression of IL-27 at both tension and pressure sides of studied teeth at T2-T4 was significantly lower compared with that of T0 and T1. At T5, IL-17A, IL-17F, IL-23, and IL-27 returned to the baseline level. For the control group, the cytokines were notsignificantly different at various time points. The expression of IL-17A, IL-17F, and IL-23 was positively correlated with RANKL expression at T2-T4, whereas the IL-27 was negatively correlated with RANKL expression at T2-T4. This study provided preliminary evidence that Th17 cytokines may be involved in the regulation of OTM.

Clinical partial remission (CPR) in most patients with type 1 diabetes (T1D) is observed shortly after clinical diagnosis. Increasing body weight and impaired insulin sensitivity may play a role in the pathogenesis of CPR. Several cytokines can also participate in the development of insulin resistance. To evaluate the relationship between birth weight, body mass index, and the concentrations of IL-8 and Fetuin-A, and the presence of clinical partial remission in children at the T1D onset.  The study group consisted of 134 children with a newly diagnosed T1D in whom the presence of CPR was evaluated in a further 2-year course of diabetes. The control group included 47 children withoutglucose tolerance disorders. The concentrations of IL-8 and Fetuin-A were determined by the ELISA method. CPR occurred in 75.34% of T1D patients. At T1D onset, higher values of BMI SDS in the remitters as compared to the patients without remission were observed. At the T1D onset, the concentrations of Fetuin-A (p=0.031) and IL-8 (p=0.042) were significantly higher in patients compared to those without CPR. Evaluation of Fetuin-A and IL-8 levels in patients with a newly diagnosed T1D can differentiate between patients with or without CPR.

Although there have been many studies investigating the effects of electromagnetic fields on humans cells and tissues, the effects of radiofrequency electromagnetic fields exposure on the cells of the immune system are still controversial. To investigate the effects of 1800 MHz RF-EMF exposure on peripheral blood mononuclear cells by measuring T helper cells count and the cytokine profile under different conditions of durations and distances. The peripheral blood mononuclear cells (PBMCs) from healthy human subjects were exposed to 1800 MHz RF-EMF, with durations of 15, 30, 45, and 60 minutes and distances of 5 and 25 cm. The effects of RFEMF exposure on the number of CD4+ T cells, and the expression of IL-2,IL-10, and IL-17a after 48 hours of culture were evaluated using flow cytometry. Our findings indicated that closer distance and longer exposure inducedlower number of CD4+ T cells. Similarly the percentagesof IL-2, IL-10 and IL-17a expressing CD4+ T cells weredecreased significantly. The number of IL-2 expressing CD4+T cells wasincreased significantly as the duration of exposure was increased, but the number was decreased after 60 minutes exposure when compared with control group with no exposure. Exposure to RF-EMF for 60 minutes at 5 cm distance causes a significant reduction in the number of CD4+ T cells, IL-2, IL-10 and IL-17a expressing T cells.

Anti-programmed cell death 1(anti-PD-1) antibodies are immune checkpoint inhibitors (ICIs) used as a treatment option for a number of cancers to expand lifespan. However, the toxicity caused by ICIs is often unpredictable and can be occasionally life-threatening.

To evaluate the immune-related adverse events (irAEs) induced by Camrelizumab, an anti-PD-1 antibody in a patient with gastric cancer.

The patient was a 32-year-old man who was diagnosed with stage IIIA gastric adenocarcinoma (cT4aN1M0) in pre-operative evaluation. However, pancreatic invasion and peritoneal metastasis were found during surgery. He received a three-week cycle of 200 mg Camrelizumab combined with systemic chemotherapy. After the fifth administration of Camrelizumab, the patient displayed irAE mimicking Behcet's disease with oral and penile ulcers, skin and abdominal incision lesions. Camrelizumab was permanently discontinued, but systemic chemotherapy was continued. The symptoms were improved with discontinuation of Camrelizumab and administration of glucocorticoid and immunosuppressive agents for 8 weeks, but suspicious liver metastases occurred and carbohydrate antigen 19-9 showed an increasing trend in the meantime. Given the significant improvement in the patient's symptoms after discontinuation of Camrelizumab and administration of corticosteroids and immunosuppressants, we assumed that these treatments may play a role in the rehabilitation of patients.

Severe irAEs occur at a low frequency when anti-PD-1 antibodies are used as monotherapy. Whether anti-PD-1 antibodies combined with systemic chemotherapy increase the incidence of irAEs is not certain.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. ALPS caused by defective lymphocyte homeostasis is characterized by non-malignant lymphoproliferation that often improves with age and is an autoimmune disease, mostly directed toward blood cells. This report describes a 17-year-old female with ALPS who developed skin rashes and aphthous stomatitis after using colchicine therapy owing to Familial Mediterranean Fever (FMF) with V726A heterozygous mutation in MEFV gene, hepatosplenomegaly, lymphadenopathy and pancytopenia, elevated vitamin B 12 and IL-10, elevated double-negative T cells (DNTs) and elevated immunoglobulin (Ig) G, consistent with a heterozygous germline FAS mutation [p.E261K (c.781G>A)]. In our country where genetic diseases are common due to consanguineous marriages, diseases with serious morbidity such as ALPS should be kept in mind. We should not forget that autoinflammatory diseases and familial Mediterranean fever can coexist owing to very high carrier rate in our country.