Expert Review of Clinical Immunology最新文献

Introduction: Primary Sjögren's syndrome (pSS) is an autoimmune disorder primarily affecting salivary and lacrimal glands, although about 40% of patients experience systemic complications. In this setting, the identification of patient phenotypes characterized by increased risk of extra-glandular involvement still represents an unmet need.

Areas covered: The aim of this paper is to review the scientific evidence on the utility of salivary gland biopsies in pSS, emphasizing their role in defining prognosis. In latest years, research focused on disease-specific clinical, serological, or histological features able to categorize patient prognosis. Among histopathological features, focus score and ectopic germinal centers exhibit associations with glandular and extraglandular manifestations, including higher rates of lymphomagenesis.

Expert opinion: Pathological characterization of salivary glands provides information that go beyond a mere diagnostic or classification utility, providing insights for a stratification of disease severity and for predicting systemic manifestations. Thus, a salivary gland biopsy should be offered to all patients and included in routine practice, even when not strictly required for diagnostic purposes. More advanced analysis techniques of the tissue, including immunohistochemistry and 'omics' should be further explored in longitudinal studies to boost the ability to further stratify and predict disease evolution.

Introduction: Rheumatoid arthritis (RA), the most prevalent autoimmune disease in reproductive years, exhibits a higher incidence in females, suggesting involvement of estrogens, genetics and environmental factors in disease onset. Literature shows smaller families in RA patients, driving increased interest in Assisted Reproductive Techniques.

Areas covered: This review elucidates how immunotolerance mechanisms contribute to favorable pregnancy outcomes in RA, emphasizing the need for a careful pregnancy planning to mitigate fetal complications and postnatal flares, which surpass those in the general population. A thorough medication evaluation, orchestrated by a multidisciplinary team, is imperative during pregnancy, weighing potential teratogenic effects against safer alternatives to balance medication safety with disease control. A systematic literature search on PubMed and MEDLINE, using specific terms, covered relevant academic journals up to the latest date.

Expert opinion: This narrative review comprehensively addresses pregnancy-related considerations in RA patients, prioritizing meticulous disease management with pregnancy and breastfeeding-compatible drugs in line with the latest recommendations and registry data. The focus remains on evaluating glucocorticoids, conventional, and biological disease-modifying drugs for compatibility during pregnancy and breastfeeding. Additionally, the evolving landscape of targeted synthetic drugs during pregnancy is explored, providing insights into the latest developments in rheumatological care.

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: 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.

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.