Expert Review of Clinical Immunology最新文献

Introduction: Autoimmune bullous disease (AIBD), showing blistering lesions on the skin and/or mucous membranes, is characterized by autoantibodies against various structural molecules present in keratinocyte cell surfaces and epidermal basement membrane zone. In addition to the clinical and pathological features, identification of specific autoantibodies is essential for AIBD diagnosis, and therefore corresponding methods should be well summarized and popularized.

Area covered: Currently, direct immunofluorescence using biopsy tissue specimen and indirect immunofluorescence using normal human skin, 1 M NaCl-split skin and rat bladder are primarily used to identify tissue-bound and circulating autoantibodies, respectively. Immunoblotting and enzyme-linked immunosorbent assay (ELISA) methods have been developed for detection of autoantibodies against AIBD autoantigens, including desmoglein 1, desmoglein 3, BP180, BP230, type VII collagen, laminin (LM) 332, integrin α6β4, p200 (LMγ1/LMβ4) and human serum albumin. In this review, we summarized the detailed laboratory protocols for AIBD diagnosis methods used in our three institutes (Kurume University and Osaka Metropolitan University in Japan, and Daqing Oilfield General Hospital in China) before 9 October 2024.

Expert opinion: This review will benefit both clinical practitioners and basic researchers on AIBD. In the future, simpler and easier AIBD diagnostic algorithms using a smaller number of tests should be established.

Introduction: Accumulative evidence indicates that both innate and adaptive immunity are involved in pathogenesis of Still's disease, an autoinflammatory disease. With Increasing insights into the pathogenesis of Still's disease coupled with the availability of emerging targeted therapeutics, it may be the unmet need for personalizing therapy and achieving a treat-to-target goal. We aim to summarize the available evidence regarding immunopathogenesis of Still's disease and therapeutic strategies based on immunologic endotypes.

Areas covered: We searched MEDLINE database using the PubMed interface and reviewed relevant English-language literature from 1971 to 2024. This review focuses on the existing evidence on pathophysiology and immunological endotypes of Still's disease and their implications for personalized strategies for patients with this disease.

Expert opinion: Targeting the complex immunopathogenesis of Still's disease, emerging new agents are available for treatment, including biologic disease-modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) such as Janus kinase inhibitors (JAKi). According to the updated evidence, meta-analyses, and recommendations, we propose a flow chart emphasizing personalized therapeutic strategies based on immunological endotypes. Hopefully, the therapeutic strategy might help guide the optimal selection of b/tsDMARDs to achieve a 'treat-to-target' goal in Still's disease. This proposed flow chart will be updated as newer evidence emerges.

Introduction: Interstitial lung disease (ILD) is a potential severe complication of various rheumatic diseases, typically connective tissue diseases (CTD), associated with significant morbidity and mortality. ILD may occur during the course of the disease but may also be its first manifestation. Several cell types are involved in ILD's pathogenesis, and if not controlled, pulmonary inflammation may lead to pulmonary fibrosis.

Areas covered: We searched PubMed, Medline, and the Cochrane Library for papers published between 1995 and February 2017 in the first version, and between 2017 and April 2023 using combinations of words. The most frequent systemic rheumatic diseases associated with ILD are systemic sclerosis (SSc), rheumatoid arthritis (RA), and idiopathic inflammatory myositis. Treatment and monitoring guidelines are still lacking, and current treatment strategies have been extrapolated from the literature on SSc and established treatments for non-pulmonary systemic rheumatic manifestations.

Expert opinion: Given the complexity of diagnosis and the paucity of treatment trials, managing CTD patients with ILD is challenging. It requires the skills of multidisciplinary CTD-ILD clinics including at least rheumatologists and lung specialists.

Introduction: Pain in both peripheral and axial joints is a major symptom in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Emerging evidence demonstrates pain mechanisms, beyond those related to inflammation or joint damage, based on aberrant processing of nociceptive stimuli peripherally as well as centrally. The Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway has been implicated in the processing of pain beyond its role in mediating inflammation and inhibitors of this pathway approved for the treatment of axSpA and PsA have been shown to alleviate a broad array of pain outcomes in both axial and peripheral joints.

Areas covered: We review recent definitions and standardization of the nomenclature for categorizing chronic pain according to causality, assessment tools to evaluate nociplastic pain, the pathophysiologic role of JAK-STAT signaling in nociplastic pain, evidence for the presence of nociplastic pain in axSpA and PsA, and the impact of JAK inhibitors (JAKi) on pain outcomes in clinical trials (PubMed: 01/01/2019-04/01-2024).

Expert opinion: Nociplastic pain assessment has been confined almost entirely to the use of a limited number of questionnaires in cross-sectional studies of these diseases. Though effective for alleviating pain, it is unclear if JAKi specifically impact nociplastic pain.

Background: Glioblastoma (GBM) is an aggressive cancer with limited treatment options. Immunotherapy targeting CD69, an early activation marker on T cells, has shown promise in preclinical models of non-CNS malignancies. This study investigates anti-CD69 therapy alone or in combination with anti-PD-1 in a preclinical GBM model.

Research design and methods: CD69 expression in GBM patient tissues was analyzed using the TCGA database. Therapeutic efficacy of anti-CD69 was tested in a murine GBM model with different regimens. Immune cell populations in the tumor microenvironment (TME) were assessed by flow cytometry.

Results: Increased CD69 expression was observed in GBM patients compared to normal brain tissue and was associated with worse prognosis. Anti-CD69 treatment reduced percentages of CD69⁺ immune cells but did not improve survival in GBM-bearing mice. Increased PD-1 expression on NK cells was observed following anti-CD69 treatment. Anti-CD69 treatment was not improved by the addition of anti-PD-1 in vivo.

Conclusions: This is the first study evaluating anti-CD69 therapy in a preclinical GBM model. Despite promising preclinical data in other cancers, anti-CD69 monotherapy or combination therapy with anti-PD-1 did not improve survival in this GBM model.

Introduction: Postpartum mood disorders are heterogenous disorders and comprise postpartum psychosis and postpartum depression. Evidence is accumulating that systemic monocyte/macrophage activation, low-grade inflammation and (premature senescence related) T cell defects increase the risk for mood disorders outside pregnancy by affecting the function of microglia and T cells in the emotional brain (the cortico-limbic system) leading to inadequate mood regulation upon stress.

Areas covered: The evidence in the literature that similar immune dysregulations are present in postpartum mood disorders.

Results: The physiological postpartum period is characterized by a rapid T cell surge and a mild activation of the monocyte/macrophage system. Postpartum mood disorder patients show a diminished T cell surge (including that of T regulatory cells) and an increase in low grade inflammation, that is, an increased inflammatory state of monocytes/macrophages and higher levels of serum pro-inflammatory cytokines.

Expert opinion: Anti-inflammatory agents (e.g. COX-2 inhibitors) and T cell boosting agents (e.g. low-dose IL-2 therapy) should be further investigated as treatment. The hypothesis should be investigated that postpartum mood disorders are active episodes (triggered by changes in the postpartum immuno-endocrine milieu) in ongoing, dynamically fluctuating aberrant neuro-immune-endocrine trajectories leading to mood disorders in women (inheritably) vulnerable to these disorders.

Objective: This study investigated the predictive value of albumin-related inflammatory markers for short-term outcomes in in-hospital cardiac arrest (IHCA) patients.

Methods: A linear mixed model investigated the dynamic changes of markers within 72 hours after return of spontaneous circulation (ROSC). Time-Dependent COX regression explored the predictive value. Mediation analysis quantified the association of markers with organ dysfunctions and adverse outcomes.

Results: Prognostic Nutritional Index (PNI) and RDW-Albumin Ratio (RAR) slightly changed (p > 0.05). Procalcitonin-Albumin Ratio (PAR1) initially increased and then slowly decreased. Neutrophil-Albumin Ratio (NAR) and Platelet-Albumin Ratio (PAR2) decreased slightly during 24-48 hours (all p<0.05). PNI (HR = 1.646, 95%CI (1.033,2.623)), PAR1 (HR = 1.69, 95%CI (1.057,2.701)), RAR (HR = 1.752,95%CI (1.103,2.783)) and NAR (HR = 1.724,95%CI (1.078,2.759)) were independently associated with in-hospital mortality. PNI (PM = 45.64%, 95%CI (17.05%,87.02%)), RAR (PM = 45.07%,95%CI (14.59%,93.70%)) and NAR (PM = 46.23%,95%CI (14.59%,93.70%)) indirectly influenced in-hospital mortality by increasing SOFA (central) scores. PNI (PM = 21.75%, 95%CI(0.67%,67.75%)) may also indirectly influenced outcome by increasing SOFA (renal) scores (all p < 0.05).

Conclusions: Within 72 hours after ROSC, albumin-related inflammatory markers (PNI, PAR1, RAR, and NAR) were identified as potential predictors of short-term prognosis in IHCA patients. They may mediate the adverse outcomes of patients by causing damages to the central nervous system and renal function.

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is an immune-mediated, inflammatory, multisystemic disease that is considered a form of ANCA-associated vasculitis and whose association with asthma and blood and tissue eosinophilia differentiate it from other types of vasculitis. Nevertheless, diagnosis of EGPA may be difficult or delayed not only because of the rarity of the disease, but also because other diseases can present with similar manifestations.

Areas covered: We review a series of key areas in EGPA, namely, laboratory and clinical indicators of disease, diagnosis, role of biomarkers, induction and maintenance therapy, and use of traditional and novel drugs. This narrative review was based on a thorough search of PubMed.

Expert opinion: Clinicians should be aware of the limitations of available tools for diagnosing EGPA, and more efforts should be made to identify clinical and laboratory red flags, with the purpose of achieving an early diagnosis before irreversible damage occurs. New effective therapies are available, although future research should target an approach that spares glucocorticoids, reduces the risk of flares and organ damage, and maintains long-term remission with minimum adverse effects.

Objective: To probe the involvement of long noncoding RNA zinc finger antisense 1 (ZFAS1)/microRNA (miR)-186-5p axis in inhibiting oxidative stress in myocardial ischemia-reperfusion injury (MIRI) by targeting B-cell translocation gene 2 (BTG2).

Methods: The MIRI mice model was established by ligating the left anterior descending branch of the left coronary artery in C57BL/6 mice. The in vitro MIRI model was constructed by hypoxia and reoxygenation of HL-1 cardiomyocytes. Cardiomyocyte apoptosis and the extent of myocardial injury in mice were detected. The apoptosis rates, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in HL-1 cells were assessed. The relationship among ZFAS1, miR-186-5p, and BTG2 was verified.

Results: High ZFAS1 and BTG2 levels and low miR-186-5p levels were demonstrated in I/R-injured myocardial tissues and in H/R-treated cardiomyocytes. Interference with ZFAS1 or elevation of miR-186-5p inhibited apoptosis and oxidative stress in H/R model cardiomyocytes and I/R-injured myocardial tissues. Overexpressing BTG2 impaired the ameliorative effects of miR-186-5p on MIRI. ZFAS1 negatively regulated miR-186-5p expression by acting as a molecular sponge. miR-186-5p targeted to regulate BTG2 negatively.

Conclusion: Interfering with ZFAS1 can upregulate miR-186-5p and thus inhibit BTG2 expression, thereby ameliorating MIRI.

Introduction: Cardiovascular disease (CVD) is the leading cause of morbidity globally, with chronic inflammation as a key modifiable risk factor. Toll-like receptors (TLRs), pivotal components of the innate immune system, including TLR-3, -7, -8, and -9 within endosomes, trigger intracellular cascades, leading to inflammatory cytokine production by various cell types, contributing to systemic inflammation and atherosclerosis. Recent research highlights the role of endosomal TLRs in recognizing self-derived nucleic acids during sterile inflammation, implicated in autoimmune conditions like myocarditis.

Areas covered: This review explores the impact of endosomal TLRs on viral infections, autoimmunity, and inflammatory responses, shedding light on their intricate involvement in cardiovascular health and disease by examining literature on TLR-mediated mechanisms and their roles in CVD pathophysiology.

Expert opinion: Removal of endosomal TLRs mitigates myocardial damage and immune reactions, applicable in myocardial injury. Targeting TLRs with agonists enhances innate immunity against fatal viruses, lowering viral loads and mortality. Prophylactic TLR agonist administration upregulates TLRs, protecting against fatal viruses and improving survival. TLRs play a complex role in CVDs like atherosclerosis and myocarditis, with therapeutic potential in modulating TLR reactions for cardiovascular health.