Expert Review of Clinical Immunology最新文献

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune rheumatic disease characterized by microvascular alterations, immunopathology, and widespread fibrosis involving various organs. It is considered difficult to treat due to several reasons: complex pathogenesis, heterogeneity, late diagnosis, limited treatment options for certain organ manifestations, lack of personalized medicine.

Areas covered: This review presents the heterogeneity, survival and organ manifestations with their risk factors of systemic sclerosis and their current treatment options, while drawing attention to difficult-to-treat forms of the disease, based on literature indexed in PubMed.

Expert opinion: Despite recent advances in the management of SSc over the last decades, the disease presents significant morbidity and mortality. Although available treatment protocols brought significant advancements in terms of survival in SSc-associated interstitial lung disease and pulmonary arterial hypertension, less success has been achieved in the treatment of Raynaud's phenomenon and digital ulcers and the results are modest in case of heart, gastrointestinal, and renal manifestations. There are patients who do not respond to treatment and deteriorate even with adequate therapy. They can be considered difficult-to treat (D2T) cases. We have created a possible score system based on the individual organ manifestations and highlighted treatment options for the D2T SSc category.

Introduction: Atopic dermatitis (AD) is a common, chronic inflammatory skin disorder driven by an intricate interplay of genetic, environmental, and immunological factors.

Areas covered: As a clinically heterogenous condition, AD may be stratified into subtypes based on factors including, chronicity, immunoglobulin E levels, severity, age, and ethnicity. Transcriptomic and proteomic analyses in skin and blood help elucidate the underlying molecular mechanisms of these AD subtypes, referred to as AD endotypes. Further characterizing AD endotypes using reliable biomarkers can facilitate the development of more effective and personalized therapeutics and improve our tools for monitoring disease progression and therapeutic response across a diverse subset of patients. Here, we aim to provide perspective on the latest research regarding AD stratification using skin and blood-based studies and insight into the implications of these findings on the future of AD research and clinical practice.

Expert opinion: The precise stratification of AD endotypes will allow for the development of reliable biomarkers and a more personalized medical treatment approach. Clinical practice and trials will eventually be able to bridge clinical with molecular data to optimize individualized treatments and more effectively monitor treatment response.

Introduction: Giant cell arteritis (GCA) is a large vessel (LV) vasculitis that affects people aged 50 years and older. Classically, GCA was considered a disease that involved branches of the carotid artery. However, the advent of new imaging techniques has allowed us to reconsider the clinical spectrum of this vasculitis.

Areascovered: This review describes clinical differences between patients with the cranial GCA and those with a predominantly extracranial LV-GCA disease pattern. It highlights differences in the frequency of positive temporal artery biopsy depending on the predominant disease pattern and emphasizes the relevance of imaging techniques to identify patients with LV-GCA without cranial ischemic manifestations. The review shows that so far there are no well-established differences in genetic predisposition to GCA regardless of the predominant phenotype.

Expert commentary: The large branches of the extracranial arteries are frequently affected in GCA. Imaging techniques are useful to identify the presence of 'silent' GCA in people presenting with polymyalgia rheumatica or with nonspecific manifestations. Whether these two different clinical presentations of GCA constitute a continuum in the clinical spectrum of the disease or whether they may be related but are definitely different conditions needs to be further investigated.

Introduction: Castleman disease (CD) is a benign lymphoproliferative disease causing severe systemic inflammation. Interleukin-6 (IL-6) is a major pathogenesis of multicentric CD (MCD), but only 30-60% of patients respond to IL-6 inhibitors. Novel agents for IL-6 inhibitor-refractory cases are needed. Clinical data and samples are being collected on a large scale and the clinical, pathological, and pathogenetic aspects are being elucidated.

Areas covered: The pathological and clinical classification of CD is outlined. Focusing on idiopathic MCD (iMCD), this review identifies therapeutic targets and summarizes currently recommended drugs and promising therapeutic candidates.

Expert opinion: The pathogenesis of MCD has been implicated in the activation of the Janus kinase (JAK)-transcriptional signaling activator (STAT) 3 pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt/mechanical target of rapamycin (mTOR) signaling pathway. iMCD-TAFRO (thrombocytopenia, anasarca, fever/elevated CRP, reticulin myelofibrosis/renal dysfunction, organ enlargement) is resistant to IL-6 inhibitors, and cyclosporine and mTOR inhibitors are sometimes effective. JAK inhibitors and mTOR inhibitors may be therapeutic agents for iMCD. Recently, we have shown that peripheral helper T (Tph) cell abnormalities are at the core of iMCD pathogenesis. Therapies targeting chemokine (C-X-C motif) ligand 13 (CXCL13) produced by Tph cells and blocking the Tph-CXCL13-B cell pathway may satisfy unmet need in refractory cases.

Background: We aimed to explore simple and effective clinical parameters or combinations to predict coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease (KD).

Design and methods: This retrospective cohort study included pediatric patients with KD from January, 2013 to December, 2022. Multiple demographic and clinical data were collected, collated, and calculated from the medical records. Then they were divided into the coronary artery dilation and aneurysm formation group or the non-coronary artery dilation and aneurysm formation group. Lymphocyte-C-reactive protein ratio (LCR) was transformed into its natural logarithm and expressed as lnLCR.

Results: A total of 64 pediatric patients with KD were enrolled in this cohort study after 1:3 propensity score matching (PSM). For each unit increase in lnLCR, the possibility of coronary artery dilation and aneurysm formation decreased to 0.419 times the original value. The areas under the receiver operating characteristic (ROC) curves of lnLCR combined with albumin (ALB), ALB, and lnLCR to classify pediatric patients with KD into the coronary artery dilation and aneurysm formation group were 0.781, 0.692, and 0.743, respectively.

Conclusion: LCR combined with ALB upon admission is a promising predictor of coronary artery dilation and aneurysm formation in pediatric patients with KD.

Background: Rising cancer-related mortality underscores the importance of biomarkers for treatment and prognosis, with Chromosome Segregation 1 Like (CSE1L) linked to various cancers yet its roles remain partially understood. This study investigates CSE1L's expression and oncogenic mechanisms in solid tumors.

Research design and methods: We analyzed multi-omics data from 31 solid tumors, measured CSE1L in 41 head and neck carcinoma patients post-chemotherapy via qRT-PCR, and evaluated the impact of CSE1L knockdown on cell proliferation in A549 and HepG2 cells.

Results: In this study, we observed significantly elevated levels of CSE1L RNA in 13 tumor tissues and protein levels in 8 tumor tissues compared to their corresponding adjacent normal tissues. Additionally, our investigation unveiled a correlation between heightened CSE1L expression in tumor tissues and worsened patient prognosis, poor response to immunotherapy, and diminished effectiveness of neoadjuvant chemotherapy. Through an analysis of CSE1L mechanisms, we discovered its potential involvement in promoting tumor cell proliferation, enhancing drug resistance, and influencing immune infiltration, thereby impacting patient prognosis and treatment outcomes. Finally, we delved into the potential mechanisms underlying upregulation of CSE1L in tumor tissues.

Conclusion: Our findings demonstrate that CSE1L promotes tumor development in various malignancies, highlighting its potential as both a therapeutic target and prognostic indicator.

Introduction: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented global health challenges since its emergence in December 2019. The rapid availability of vaccines has been estimated to save millions of lives, but there is variation in how individuals respond to vaccines, influencing their effectiveness at an individual, and population level.

Areas covered: This review focuses on human genetic factors influencing the immune response and effectiveness of vaccines, highlighting the importance of associations across the HLA locus. Genome-Wide Association Studies (GWAS) and other genetic association analyses have identified statistically significant associations between specific HLA alleles including HLA-DRB1*13, DBQ1*06, and A*03 impacting antibody responses and the risk of breakthrough infections post-vaccination. Relationships between these associations and potential mechanisms and links with risks of natural infection or disease are explored, and this review concludes by emphasizing how understanding the mechanisms of these genetic determinants may inform the development of tailored vaccination strategies.

Expert opinion: Although complex, we believe these findings from the SARS-CoV2 pandemic offer a unique opportunity to understand the relationships between HLA and infection and vaccine response, with a goal of optimizing individual protection against COVID-19 in the ongoing pandemic, and possibly influencing wider vaccine development in the future.

Introduction: The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the subsequent coronavirus disease 2019 (COVID-19) pandemic has raised questions about its impact on pediatric asthma. This review analyzes the latest research to offer a comprehensive understanding of the dynamics between COVID-19 and pediatric asthma.

Areas covered: This narrative review examines the effects of COVID-19 on pediatric asthma, exploring clinical outcomes, immune responses, recommended treatments, the impact of SARS-CoV-2 strains, and COVID-19 vaccination. Data were sourced from databases (PubMed, Embase, and BioRxiv/MedRxiv) from January 2020 to November 2023.

Expert opinion: In response to the COVID-19 pandemic, the international scientific community rapidly developed extensive knowledge, demonstrating unprecedented cooperation. Despite these advances, questions remain about SARS-CoV-2 infection and pediatric asthma. Most research consists of epidemiological studies with varying methods, sometimes yielding contradictory results. While asthma generally did not increase the risk of severe COVID-19 in children, uncontrolled asthma was a risk factor, highlighting the importance of maintaining asthma management. Telemedicine has proven effective for asthma control and will continue to grow, despite its limitations. Notably, allergic asthma may have a protective role against severe COVID-19. We recommend COVID-19 vaccination in the pediatric age group, including those with asthma.

Objectives: There is scarce data in the literature concerning the anti-GAD65 antibodies (GAD-Abs) autoimmunity in the Omani population.

Methods: Retrospective cohort study included GAD-Abs positive patients (n = 444) presented to a tertiary referral center in Oman from January 2005 until January 2018, with a five-year follow-up to study the cancer association and mortality outcomes.

Results: Out of 444 patients, 27 patients (6.1%) showed GAD-Abs related neurological disorders. Adult age group was significantly associated with more GAD-Abs related neurological manifestations compared to pediatric and adolescents age group (p = 0.045). There was no association between the presence or absence of neurological manifestations with diabetes mellitus nor the titer level of GAD-Abs. Refractory status epilepticus and stiff person syndrome were the main causes of death in patients with neurological manifestations over five years and none of them found to have associated cancer.

Conclusion: The GAD-Abs autoimmunity represents a spectrum of neurological manifestations with variable severity and outcome among Omanis with positive GAD-Abs testing. The results of this study will serve as a platform for future studies to address the impact of GAD-Abs autoimmunity on the morbidity, mortality and treatment efficacy in the Omani population.