Immunological Medicine最新文献

Early diagnosis and timely therapeutic intervention are clinical challenges of rheumatoid arthritis (RA), especially for treatment-resistant or difficult-to-treat patients. Little is known about the immunological mechanisms involved in refractory RA. In this review, we summarize previous research findings on the immunological mechanisms of treatment-resistant RA. Genetic prediction of treatment-resistant RA is challenging. Patients with and without anti-cyclic citrullinated peptide autoantibodies are considered part of distinct subgroups, especially regarding long-term clinical prognosis and treatment responses. B cells, T cells and other immune cells and fibroblasts are of pathophysiological importance and are associated with treatment responses. Finally, we propose a new hypothesis that stratifies patients with RA into two subgroups with distinct immunological pathologies based on our recent immunomics analysis of RA. One RA subgroup with a favorable prognosis is characterized by increased interferon signaling. Another subgroup with a worse prognosis is characterized by enhanced acquired immune responses. Increases in dendritic cell precursors and diversified autoreactive anti-modified protein antibodies may have pathophysiological roles, especially in the latter subgroup. These findings that improve treatment response predictions might contribute to future precision medicine for RA.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by inflammation in multiple organs. A few treatments for SLE currently exist, including antimalarials, glucocorticoids, immunosuppressants, and two recently approved antibody agents; however, an unmet medical need remains for SLE. In addition, developing new drugs targeting SLE is a challenge since no specific biomarkers exist for the prediction of disease progression or drug response. A new drug candidate, E6742, is a specific antagonist of the toll-like receptors 7/8. To address the challenges for drug development in SLE, the process of developing E6742 utilizes a unique system of the Japan Agency for Medical Research and Development (AMED), the Cyclic Innovation for Clinical Empowerment (CiCLE) program. In the CiCLE program, a Phase 1 study in healthy adults was completed (NCT04683185) and a Phase 1/2 study in patients with SLE is on-going (NCT05278663). One of the potential benefits of this program is to conduct academia-led clinical research to identify specific biomarkers for E6742 in parallel with clinical studies (UMIN000042037). The aim of this review is to present current progress within the strategic collaboration of the AMED CiCLE program that optimize clinical development for patients with SLE.

Metabolic syndromes including obesity and diabetes are the most common health issues due to insulin resistance, disturbance in glucose homeostasis, lack of exercise, and improper diet. The current study was planned to evaluate the potential effects of regular diet with fortified yogurt on blood glycemia and anthropometric responses. Plain yogurt was procured from the local market, and then it was fortified with calcium. Furthermore, the subsequent effect of fortified yogurt on blood glucose, insulin, and anthropometric measurements was assessed at different time intervals. A total of 40 healthy females and males aged about 20 years with a normal BMI range (20-24.9 kg/m²) were recruited within the Government College University Faisalabad. Participants filled out the habits Performa, stress factors questionnaire, and activity questionnaire. Blood glucose (BG) and visual analogous scale (VAS) performs were also taken in the fasting stage and then assigned treatment was given. After 15, 30, 45, 60, 90, and 120 min intervals VAS and BG estimation was carried out. The results shows that fortified yogurt contained a higher amount of calcium. Likewise, a similar trend was observed for the desire to eat, a feeling of fullness, palatability, physical comfort, and overall acceptability. The results obtained from various analyses were statistically evaluated.

Osteoclasts, derived from the monocyte/macrophage line of bone marrow hematopoietic stem cell progenitors, are the sole bone-resorbing cells of the body. Conventional osteoclast differentiation requires macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. Rheumatoid arthritis (RA) is the most prevalent systemic autoimmune disease and inflammatory arthritis characterized by bone destruction. Increased levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in the serum and joints, cause excessive bone destruction. We have recently reported that stimulation of human peripheral blood monocytes with TNF-α and IL-6 induces the differentiation of osteoclasts with bone resorption activity. This review presents the functional differences between representative osteoclasts, conventional RANKL-induced osteoclasts, and recently identified proinflammatory cytokine (TNF-α and IL-6)-induced osteoclasts in RA patients. We believe novel pathological osteoclasts associated with RA will be identified, and new therapeutic strategies will be developed to target these osteoclasts and prevent the progression of bone destruction.

YKL-40 is implicated in inflammation and tissue repair, but no reports have investigated its involvement in myositis in polymyositis (PM) and dermatomyositis (DM). Therefore, we aimed to investigate the relationship between YKL-40 and PM/DM. We retrospectively enrolled 35 patients diagnosed with PM/DM along with 26 healthy controls (HCs). Both PM and DM were diagnosed according to Bohan and Peter's criteria. Serum YKL-40 levels were measured, age-corrected to YKL-40 percentile values, and compared to HCs. Patients with myositis without interstitial lung disease were also enrolled and compared to HCs. Immunofluorescence staining was performed to identify YKL-40-positive inflammatory cells in muscle biopsy samples from two patients each with PM and DM. Age-corrected serum YKL-40 levels were significantly higher in patients with PM/DM compared to HCs with and without lung disease; however, these levels decreased significantly after treatment. Immunohistochemical analysis showed infiltration of YKL-40-positive inflammatory cells into the intramuscular sheath and perimuscular membrane. Immunofluorescence staining showed CD68 expression in YKL-40-positive inflammatory cells, suggesting that these cells were macrophages. To the best of our knowledge, this is the first study to demonstrate that YKL-40-positive macrophages are present in PM and DM, indicating that YKL-40 may be involved in PM/DM.

Abatacept (ABT) is a biological disease-modifying antirheumatic drug (bDMARDs) for rheumatoid arthritis (RA) when conventional synthetic DMARDs are ineffective. We aimed to evaluate the long-term effects of ABT on joint destruction in patients treated for over 2 years. Radiographic progression was evaluated using the van der Heijde-modified Total Sharp Score (mTSS) by two rheumatologists at ABT initiation and after 2 years. Multivariate logistic regression analysis was used to identify factors associated with structural remission, defined as the mean annual change in mTSS ≤0.5. Among the 111 patients included, 48 discontinued, and 63 continued ABT treatment until radiographic evaluation was performed. The rate of patients who achieved estimated TSS REM (yearly progression of van der Heijde modified total Sharp scores ≤0.5) was significantly lower in ABT-dropouts than in the ABT-continued group (69% vs. 48%, p = .0336 by Fisher's exact test). Among the continued ABT cases, concomitant glucocorticoid treatment at ABT initiation was the strongest negative predictive factor of estimated TSS REM in univariate and multivariate logistic regression analyses. Radiographic progression after ABT administration should be evaluated separately for dropout and non-dropout cases. Glucocorticoids at the initiation of ABT may serve as a predictive factor for joint destruction in long-term ABT use.

Small bowel adenocarcinoma (SBA) is a rare tumor with an unfavorable prognosis, and due to its rarity, few studies on its treatment are available. Chemotherapy remains the standard of treatment in advanced disease. Recently immunotherapy has demonstrated to be a valid therapeutic option for many solid tumors. We reviewed the data published in literature to understand the impact of immunotherapy in this cancer.

A 56-year-old woman was treated for rheumatoid arthritis for 17 years with methotrexate (MTX). Night sweats, fever and weight loss made her visit our hospital. Although levofloxacin failed to resolve her fever, she was suspected of having sepsis because of pancytopenia, elevated procalcitonin and a nodular lesion in the lung. After urgent hospitalization, she was diagnosed finally with the methotrexate-related lymphoproliferative disorder (MTX-LPD) associated with macrophage activation syndrome (MAS). Her general condition was improved with MTX withdrawal and 5-day high-dose glucocorticoid administration. Thus, even when the patient was critically ill with MAS, no cytotoxic agents were required to control MTX-LPD.

Immune system plays a significant role in preventing and controlling diseases. Some studies reported the beneficial effects of grapes and their products on immunity. However, their results are controversial. This review aimed to discuss the effects of grapes and their products on immune system and their mechanisms of action. Although various in-vio and in-vitro studies and some human studies suggested that grapes and their products may help to improve the immune system's function, clinical trials in this area are limited and inconsistent.In conclusions, although, consumption of grapes and their products may help to having a healthy immune syste, further studies particularly human studies are required to clarify the precise effects of them and their mechanisms regarding immune system.

Activated phosphatidyl inositol 3-kinase-delta syndrome (APDS) due to gain-of-function variant in the class IA PI3K catalytic subunit p110δ (responsible gene: PIK3CD) was described in 2013. The disease is characterized by recurrent airway infections and bronchiectasis. It is associated with hyper-IgM syndrome due to the defect of immunoglobulin class switch recombination and decreased CD27-positive memory B cells. Patients also suffered from immune dysregulations, such as lymphadenopathy, autoimmune cytopenia or enteropathy. T-cell dysfunction due to increased senescence is associated with a decrease in CD4-positive T lymphocytes and CD45RA-positive naive T lymphocytes, along with increased susceptibility to Epstein-Barr virus/cytomegalovirus infections. In 2014, loss-of-function (LOF) mutation of p85α (responsible gene: PIK3R1), a regulatory subunit of p110δ, was identified as a causative gene, followed in 2016 by the identification of the LOF mutation of PTEN, which dephosphorylates PIP3, leading to the differentiation of APDS1 (PIK3CD-GOF), APDS2 (PIK3R1-LOF) and APDS-L (PTEN-LOF). Since the pathophysiology of patients with APDS varies with a wide range of severity, it is crucial that patients receive appropriate treatment and management. Our research group created a disease outline and a diagnostic flow chart and summarized clinical information such as the severity classification of APDS and treatment options.