Archivum Immunologiae et Therapiae Experimentalis

Liệu pháp miễn dịch với tế bào đuôi gai (DCs) được sản xuất ex vivo được báo cáo là ít độc tính và có hiệu quả đa dạng trong điều trị ung thư. Các kháng nguyên tổng hợp thường được sử dụng cho liệu pháp miễn dịch, đặc biệt cho những bệnh nhân có bệnh ổn định sau điều trị trước đó. Chúng tôi đã mô tả tác động của liệu pháp miễn dịch dựa trên DCs nạp peptide đối với một bệnh nhân bị ung thư tuyến trước phổi tái phát sau khi phẫu thuật cắt bỏ có đặc điểm phế quản phế nang, đồng thời có bệnh Takayasu và viêm gan B mãn tính. Vào tháng 1 năm 2010, một bệnh nhân 61 tuổi đã nhận bốn mũi tiêm dưới da DCs nạp epitop MUC1 và MAGE-3 hai tuần một lần. Thêm vào đó, bệnh nhân đã nhận ba mũi tiêm tăng cường ba tuần một lần sau 7 tháng từ liệu trình miễn dịch đầu tiên. Thử nghiệm phản ứng quá mẫn muộn chỉ dương tính với kháng nguyên MAGE-3. Chúng tôi đã quan sát thấy sự gia tăng tế bào CD8+ đặc hiệu với MAGE-3 sau mũi tiêm đầu tiên và sau mũi tiêm thứ ba trong các lần tiêm tăng cường (từ 0,08% trước tiêm đến 0,5% sau tiêm đầu tiên; từ 0,05% trước tiêm tăng cường đến 0,24% sau mũi tiêm thứ ba). Các chụp cắt lớp vi tính được thực hiện sau liệu trình đầu tiên và sau liệu trình tăng cường tiêm đến tháng 4 năm 2011 không cho thấy sự hiện diện của khối u phổi hoặc di căn. Dựa trên các yếu tố lâm sàng (không cắt bỏ hoàn toàn và đặc điểm tái phát của ung thư) cũng như sự hiện diện của phản ứng miễn dịch đặc hiệu với kháng nguyên khối u, chúng tôi có thể suy đoán rằng liệu pháp miễn dịch đã kéo dài thời gian không bệnh ở bệnh nhân của chúng tôi. Sau hơn 16 tháng từ mũi tiêm đầu tiên, bệnh nhân vẫn không có triệu chứng của ung thư.

The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus erythematosus (SLE) is still unclear. Herein, we examined the frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells in patients with juvenile SLE and their potential relations to SLE-related clinical and laboratory parameters. The study included 35 SLE children and 20 apparently healthy controls. After baseline clinical and lab work, SLE Disease Activity Index (SLEDAI-2K) and Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI) scores were assessed. The frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells was examined using flow cytometry. SLE patients showed significantly lower frequency of NK cells and NKT cells and higher frequency of CD56bright NK cells compared to controls. Disease activity, urea, and creatinine correlated negatively with NK, but positively with CD56bright NK cells. NK and NKT cells exhibited inverse correlation with the renal biopsy activity index; however, CD56bright NK cells showed direct correlations with both activity and chronicity indices. Regarding Ped-SDI, renal, neuropsychiatry disorders, and growth failure correlated inversely with NK but directly with CD56bright NK cells. NKT cell inversely correlated with renal damage and delayed puberty. In conclusion, low frequency of NK and NKT and expansion of CD56bright NK cells are marked in juvenile SLE, particularly with activity. These changes have direct effect on renal impairment and growth failure, reflecting their potential influence on disease progression.

Air pollution is considered to be one of a risk factor for rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is commonly used as a mouse model of human RA. However, the impact of specific particulate matter (PM) components on the incidence and severity of RA has still not been established. The aim of this study was to develop an experimental model of CIA suitable to test arthritogenicity of inhaled PM. A mild form of CIA was induced in DBA1/J mice inhaled with various components of SRM 1648a PM. The incidence and severity of arthritis was assessed, and the selected serum markers of autoimmunity and inflammation were determined. Clinical arthritis was observed from the booster CII immunisation onward. Anti-cyclic citrullinated peptide antibodies, a diagnostic marker of RA, were detected in serum of these mice. All inhaled pollutants, crude PM, PM with reduced organic content, ferric, and silica nanoparticles markedly increased CIA incidence and severity. The fastest progression of CIA development was caused by crude PM and was linked to enhanced serum levels of anti-CII IgG, the prominent arthritogenic autoantibodies. On the other hand, inhaled nanoparticles enhanced serum levels of TNFα, a major proinflammatory arthritogenic cytokine. We recommend this experimental model of mild CIA to test the mechanisms of arthritis exacerbation by inhaled air pollutants. Further studies are necessary to determine whether PM-aggravated arthritis is caused by inflammatory mediators translocated from inflamed lung into systemic circulation or whether PM translocated into the bloodstream directly exacerbate joint inflammation.

Fully human antibodies from transgenic animals account for an increasing number of new therapeutics. After immunization, diverse human monoclonal antibodies of high affinity can be obtained from transgenic rodents, while large animals, such as transchromosomic cattle, have produced respectable amounts of specific human immunoglobulin (Ig) in serum. Several strategies to derive animals expressing human antibody repertoires have been successful. In rodents, gene loci on bacterial artificial chromosomes or yeast artificial chromosomes were integrated by oocyte microinjection or transfection of embryonic stem (ES) cells, while ruminants were derived from manipulated fibroblasts with integrated human chromosome fragments or human artificial chromosomes. In all strains, the endogenous Ig loci have been silenced by gene targeting, either in ES or fibroblast cells, or by zinc finger technology via DNA microinjection; this was essential for optimal production. However, comparisons showed that fully human antibodies were not as efficiently produced as wild-type Ig. This suboptimal performance, with respect to immune response and antibody yield, was attributed to imperfect interaction of the human constant region with endogenous signaling components such as the Igα/β in mouse, rat or cattle. Significant improvements were obtained when the human V-region genes were linked to the endogenous CH-region, either on large constructs or, separately, by site-specific integration, which could also silence the endogenous Ig locus by gene replacement or inversion. In animals with knocked-out endogenous Ig loci and integrated large IgH loci, containing many human Vs, all D and all J segments linked to endogenous C genes, highly diverse human antibody production similar to normal animals was obtained.

The rich bacterial flora of oral cavity is controlled by innate immune response, including antibacterial peptides and among them human neutrophil peptides 1–3 (HNP1-3). The knowledge of the involvement of HNPs in innate and acquired immunity of the periodontium is fragmentary. The aim of the study was to assess alterations in HNP1-3 levels in the gingival crevicular fluid (GCF) of chronic periodontitis patients before and after nonsurgical periodontal therapy. Nineteen patients with chronic periodontitis were qualified to the study. After periodontal examination, one site with pocket depth (PD) ≥4 mm was selected. All the patients received periodontal treatment involving scaling and root planing with additional systemic antibiotic therapy (Amoxicillin 375 mg three times daily and Metronidazole 250 mg three times daily for 7 days). Prior to therapy, 3 and 6 months after it, clinical periodontal parameters were measured and GCF was collected from previously chosen site. The level of HNP1-3 in GCF was determined by means of a commercially available enzyme-linked immunoassay kit. The periodontal therapy caused a statistically significant (p < 0.001) decrease in all the assessed clinical parameters at the sites of sample collection except for bleeding on probing. The level of HNP1-3 per measure point showed a statistically significant increase (baseline—3 months: p = 0.05, baseline—6 months: p = 0.007). Within the limits of the study, it can be stated that nonsurgical periodontal therapy with additional systemic administration of Amoxicillin and Metronidazole increases the level of HNP1-3 in GCF.

Sphingosine 1-phosphate (S1P) has been shown to be a bioactive lipid mediator intimately involved in mediating a variety of immunological processes. In particular, S1P regulates lymphocyte cell trafficking between the lymphatic system and the blood. The lysophospholipid signals mainly through five related G protein-coupled receptor subtypes, termed S1P1 to S1P5. S1P1 seems to play an essential role in cell trafficking, as this receptor subtype promotes the egress of T and B cells from secondary lymphatic organs. This S1P1-mediated migratory response is a consequence of different S1P levels in the serum and lymphatic organs. In addition to its direct effects on lymphocyte motility, S1P strengthens cell barrier integrity in sinus-lining endothelial cells, thereby reducing lymphocyte egress out of lymph nodes. Furthermore, S1P modulates cytokine profiles in T and dendritic cells, resulting in an elevated differentiation of T helper-2 cells during the T cell activation process. It is of interest that the mode of molecular action of the novel immunomodulator FTY720 interferes with the signaling of S1P. After phosphorylation, FTY720 shares structural similarity with S1P, but in contrast to the natural ligand, phosphorylated FTY720 induces a prolonged internalization of S1P1, resulting in an impaired S1P-mediated migration of lymphocytes.

Pseudomonas aeruginosa is a major pathogen responsible for both acute and chronic infection. Known as a colonising pathogen of the cystic fibrosis (CF) lung, it is implicated in other settings such as bronchiectasis. It has the ability to cause acute disseminated or localised infection particularly in the immunocompromised. Human hormones have been highlighted as potential regulators of bacterial virulence through crosstalk between analogous “quorum sensing” (QS) systems present in the bacteria that respond to mammalian hormones. Pseudomonas aeruginosa is known to utilise interconnected QS systems to coordinate its virulence and evade various aspects of the host immune system activated in response to infection. Several human hormones demonstrate an influence on P. aeruginosa growth and virulence. This inter-kingdom signalling, termed “microbial endocrinology” has important implications for host–microbe interaction during infection and, potentially opens up novel avenues for therapeutic intervention. This phenomenon, supported by the existence of sexual dichotomies in both microbial infection and chronic lung diseases such as CF is potentially explained by sex hormones and their influence on the infective process. This review summarises our current understanding of the microbial endocrinology of P. aeruginosa, including its endogenous QS systems and their intersection with human endocrinology, pathogenesis of infection and the host immune system.

The aim of this prospective cohort study was to explore the effect of statins on long-term respiratory symptoms and pulmonary fibrosis in coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM). Patients were recruited from three tertiary hospitals, categorized into Statin or Non-statin groups, and assessed on days 0, 28, and 90 after symptoms onset to record the duration of symptoms. Pulmonary fibrosis was scored at baseline and follow-up time points by high-resolution computed tomography scans. Each group comprised 176 patients after propensity score matching. Data analysis revealed that the odds of having cough and dyspnea were significantly higher in the Non-statin group compared to the Statin group during the follow-up period. Overall, there was no significant difference in the change in pulmonary fibrosis score between groups. However, Non-statin patients with > 5 years of DM were more likely to exhibit a significantly higher fibrosis score during the follow-up period as compared to their peers in the Statin group. Our results suggest that the use of statins is associated with a lower risk of developing chronic cough and dyspnea in diabetic patients with COVID-19, and may reduce pulmonary fibrosis associated with COVID-19 in patients with long-term (> 5 years) DM.

Ficolin-2 is an activator of the complement system that acts via the lectin pathway. Complement activation plays a substantial role in the renal injury inherent to kidney transplantation. In this study, we examined the associations between ficolin-2 gene polymorphisms in exon 8 and kidney allograft function. This study comprised 270 Caucasian deceased-donor renal transplant recipients. The following parameters were recorded in each case: delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction. Among patients with DGF, we observed a significantly increased frequency of rs7851696 GT and TT genotypes as well as T allele (TT + GT vs GG OR 1.98, 95% CI 1.12–3.48, p = 0.02; T vs G OR 2.08, 95% CI 1.27–3.41, p = 0.005). There was also an increased frequency of rs4521835 GG and TG genotypes as well as G alleles; however, these differences were on the borderline of statistical significance (GG + TG vs TT, OR 1.75, 95% CI 0.98–3.12, p = 0.07; G vs T OR 1.45, 95% CI 1.00–2.09, p = 0.050). In addition, we observed an increased frequency of acute allograft rejection in carriers of ficolin-2 rs7851696 T alleles on the borderline of statistical significance (TT + GT vs GG OR 1.75, 95% CI 0.97–3.16, p = 0.08), but the frequency of T allele was significantly higher in patients with AR (T vs G OR 1.71, 95% CI 1.02–2.87, p = 0.048). The results of our study suggest that ficolin-2 rs7851696 gene polymorphism influences kidney allograft functions, with T allele increasing the risk of DGF and AR.