Expert Review of Clinical Immunology最新文献

Introduction: Non-traumatic osteonecrosis is a frequent complication in patients with autoimmune disorders, though its prevalence varies markedly depending upon the type of disorder. Understanding the causes of this difference can help uncover the underlying pathophysiology of osteonecrosis and guide the development of effective preventive and therapeutic strategies.

Areas covered: In this perspective study, we reviewed available databases, including PubMed, Cochrane Library, Scopus, and Web of Science, to explore why the risk of osteonecrosis varies among different autoimmune disorders. Is this variation primarily due to the disease's pathophysiology, the use of medications such as corticosteroids, or a combination of both? If both factors are involved, what is the extent of each contribution in this context?

Expert opinion: Non-traumatic osteonecrosis is often induced by an interaction between disease pathophysiology and corticosteroid use. In patients with different autoimmune disorders but an identical history of corticosteroid use, the risk of osteonecrosis is influenced by how the underlying pathophysiology compromises bone health. In autoimmune disorders with multiple adverse effects on bone, such as SLE (systemic lupus erythematosus), there is a much higher risk of osteonecrosis compared to disorders with minimal impact on bone health, such as celiac disease and MS (multiple sclerosis).

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: Autologous stem cell transplantation (ASCT) and cellular therapies (CTs) are emerging therapeutic options for both adult and juvenile-onset systemic sclerosis (jSSc) patients. However, most efficacy data are derived from adult studies, and it remains unclear whether adult stem cell transplant criteria are fully applicable to pediatric patients with jSSc. Given pediatric patients' unique potential for recovery and tissue remodeling, the stringent criteria used in adults need adaptation for children.

Areas covered: We reviewed the current data on indications, patient selection, and outcomes of ASCT and CTs in both adult and pediatric patients with systemic sclerosis. At a multidisciplinary expert workshop held in Hamburg, Germany, in December 2023, we developed consensus guidance on when to consider ASCT and cellular therapies in jSSc.

Expert opinion: HSCT and CT hold promise as treatment options for jSSc. Our proposed guidance aims to standardize inclusion criteria globally, enhancing comparability of outcomes across future procedures. Establishing consistent inclusion/exclusion criteria and transplant protocols will enable better data collection, interpretation, and ultimately improve outcomes and care for jSSc patients.

Background: CT-P47 is a candidate tocilizumab biosimilar that is currently in clinical development. We assessed the usability of CT-P47 self-administration via auto-injector (AI) in patients with rheumatoid arthritis (RA).

Research design and methods: This was a 12-week, single-arm, open-label, multiple-dose, Phase 3 study. Patients self-injected CT-P47 (162 mg/0.9 mL) via AI at Weeks 0 and 2, and then every other week via pre-filled syringe (PFS) from Week 4 through Week 10. The primary endpoint was POST-Self-Injection Assessment Questionnaire (SIAQ) at Week 2. Efficacy, safety, and immunogenicity were also assessed.

Results: Thirty-three patients were enrolled. Mean scores for all POST-SIAQ domains at Week 2 exceeded 8, except for 'self-confidence' (7.11) and 'satisfaction with self-injection' (7.98), indicating positive patient experiences with CT-P47 AI. Furthermore, an observer-completed checklist found that all patients successfully followed the required steps for self-injection. Efficacy, assessed by Disease Activity Score in 28 joints and its components, showed improvements from baseline to Week 12. No new safety signals were observed; the most common adverse events were leukopenia, neutropenia, and injection-site reaction, each occurring in 3 (9.1%) patients.

Conclusions: CT-P47 self-administered using an AI showed successful usability in patients with moderate-to-severe RA.

Trial registration: ClinicalTrials.gov identifier: NCT05725434.

Introduction: Inflammatory bowel diseases (IBDs), comprised of ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory diseases of the gastrointestinal tract. Clinicians and patients must vigilantly manage these complex diseases over the course of the patient's lifetime to mitigate risks of the disease, surgical complications, progression to neoplasia, and complications from medical or surgical therapies. Over the past several decades, the armamentarium of IBD therapeutics has expanded; now with biologics and advanced small molecules complementing conventional drugs such as aminosalicylates, corticosteroids and thiopurines. Significant attention has been paid to the potential of precision medicine to assist clinicians in tailoring therapeutics based on patients' genetic signatures to maximize therapeutic benefit while minimizing adverse effects.

Areas covered: In this paper, we review the published literature on genetic polymorphisms relevant to each class of IBD therapeutics.

Expert opinion: Finally, we envision a paradigm shift in IBD research toward an omics-based network analysis approach. Through global collaboration, organization and goal setting, we predict the next decade of IBD research will revolutionize existing disease frameworks by developing precise molecular diagnoses, validated biomarkers, predictive models and novel molecularly targeted therapeutics.

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: Atopic Dermatitis (AD) is a common chronic, recurrent inflammatory skin disease, characterized mainly by polymorphic skin lesions and severe itching, significantly affecting patients' physical and mental health. The pathogenesis of AD is complex, involving multiple factors such as genetics, environment, immunity, and microbiota. In terms of treatment, traditional systemic therapies are gradually being replaced by more targeted molecular immunotherapies, and the range of topical medications has become more diverse. However, research on AD treatment in special populations, such as children, pregnant women, lactating women, and the elderly, remains relatively limited.

Areas covered: This review aims to discuss the research progress on topical treatments for AD in special populations both domestically and internationally, with a focus on personalized treatment approaches. It covers many aspects such as hormones, antimicrobial drugs, small molecule drugs, nanotechnology and microecological therapies, and proposes personalized treatments for each group and problems that need to be solved by current research.

Expert opinion: Special populations have unique physiological characteristics, which may lead to different responses to topical medications. Therefore, personalized treatment strategies are especially important in this context. As insights into pathogenesis evolves, the novel therapies are on the rise, holding promise for more targeted treatment approaches.

Introduction: This article is a narrative review exploring how research in French Guiana could unlock the mysteries surrounding Alpha-Gal Syndrome (AGS), a recently identified IgE-mediated allergy with delayed reactions to exposure to non-Catarrhine mammalian-derived products. Although fewer than 10 cases have been reported across Latin America, two case series involving 11 and 18 patients with AGS have been documented in French Guiana.

Areas covered: This article discusses risk factors such as ethnicity, prior pathogen-induced immunization to α-Gal, vectors responsible for AGS, their environment and ecosystems, observed phenotypes, and therapeutic implications for sensitized individuals. Literature research was based on PubMed between 12/2023 and 08/2024, using: α-Gal/Alpha-1,3-Galactose/galactose-α 1,3-galactose/Red meat allergy/Mammalian meat allergy/Alpha gal syndrome/Antivipmyn. Grey literature from French Guiana were obtained from Prof. Loïc Epelboin.

Expert opinion: Advancing AGS research in French Guiana could yield valuable epidemiological insights, as existing data predominantly stem from European, North American, Australian, and Japanese contexts - regions with comparatively lower diversity in tick species, their mammalian hosts, associated pathogens, and parasitic infestations. Additionally, French Guiana presents unique therapeutic scenarios, such as Viperidae envenomation and transfusions under inventory constraints, that merit further investigation.

Introduction: In recent years, the understanding of atopic dermatitis (AD) pathogenetic mechanisms has expanded, and now it is recognized that Th2 immune axis dysregulation is pivotal to AD pathogenesis. The advent of biological drugs and small molecules has marked a revolution in the treatment of AD. Dupilumab, targeting IL-4 and IL-13, has been the first to demonstrate efficacy in treating moderate to severe AD by modulating type-2 inflammation pathways. Increasing knowledge of different immune axis and cytokines has fueled the development of new biologics and small molecules. JAK inhibitors, which target the JAK-STAT pathway, involved in cytokine signaling, represent a promising novel therapeutic strategy, enlarging the treatment options for moderate to severe atopic dermatitis.

Areas covered: This comprehensive review aims to provide an updated and critical overview of the drugs currently in use and under investigation for the treatment of moderate to severe AD in children and adolescents, along with addressing the unmet needs and future research perspectives.

Expert opinion: Biologics and small molecules offer the promise to enlarge the arsenal options for the treatment of AD. Since the patients' response to biologics depends on AD pheno-endotype, choosing the right biologic is crucial for ensuring therapy success.

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. High proportions of patients with CRSwNP characterized by type 2 inflammation fail to gain adequate control with conventional treatment. The application of biologics in clinics and assessments of novel biologics in clinical trials are blooming in expectations to fulfill the unmet medical needs of patients with CRSwNP with type 2 inflammation.

Areas covered: After an extensive search of PubMed, Medline, and EMBASE for the most recent evidence, we thoroughly summarize current advances in biological therapies for treating patients with CRSwNP.

Expert opinion: In recent years, biological therapy has been in the spotlight in clinical studies on CRSwNP. Biologics have proven to be efficacious in reducing nasal polyp size, alleviating CRSwNP-related symptoms, improving quality of life, and reducing the need for systemic corticosteroids or endoscopic sinus surgery for nasal polyps. The considerable efficacy and safety profile of biologics has offered patients with refractory CRSwNP another treatment option. However, some concerns remain to be addressed. Aspects such as the position of biological therapy in the management of CRSwNP, traits of patients suitable for certain biologics, etc. necessitate efforts to elucidate these unknowns in order to provide patients with tailored therapy.