Pub Date : 2026-01-27DOI: 10.1016/j.coi.2026.102726
Vivin Kokuhennadige , Elizabeth Aitken , Stephen Rogerson
Malaria during pregnancy continues to compromise maternal, fetal, and subsequently infant health. This burden has increased in Africa, though it has decreased elsewhere. Here, we provide a concise review of recent findings on malaria in pregnancy, addressing pathogenesis, immunity, offspring outcomes, and interventions. Placental alterations and inflammation accompanying Plasmodium infection result in maternal morbidity and adverse birth outcomes, with new findings indicating antenatal infection affects infant immune and neurocognitive development. Adverse outcomes from placental infection reduce over successive pregnancies, but the drivers of this protection have been challenging to uncover. Despite parasite resistance to sulfadoxine-pyrimethamine (SP), it still helps improve birth weight as an intermittent preventive treatment in pregnancy. Dihydroartemisinin-piperaquine, though more effective against parasitemia, does not improve birth outcomes when used alone or in combination with SP. Interventions targeting first-trimester infections, blood-stage parasites, and vaccines that prime defences in primigravidae would be optimal for controlling malaria in pregnancy.
{"title":"Malaria in pregnancy at the frontline: a delicate balance","authors":"Vivin Kokuhennadige , Elizabeth Aitken , Stephen Rogerson","doi":"10.1016/j.coi.2026.102726","DOIUrl":"10.1016/j.coi.2026.102726","url":null,"abstract":"<div><div>Malaria during pregnancy continues to compromise maternal, fetal, and subsequently infant health. This burden has increased in Africa, though it has decreased elsewhere. Here, we provide a concise review of recent findings on malaria in pregnancy, addressing pathogenesis, immunity, offspring outcomes, and interventions. Placental alterations and inflammation accompanying Plasmodium infection result in maternal morbidity and adverse birth outcomes, with new findings indicating antenatal infection affects infant immune and neurocognitive development. Adverse outcomes from placental infection reduce over successive pregnancies, but the drivers of this protection have been challenging to uncover. Despite parasite resistance to sulfadoxine-pyrimethamine (SP), it still helps improve birth weight as an intermittent preventive treatment in pregnancy. Dihydroartemisinin-piperaquine, though more effective against parasitemia, does not improve birth outcomes when used alone or in combination with SP. Interventions targeting first-trimester infections, blood-stage parasites, and vaccines that prime defences in primigravidae would be optimal for controlling malaria in pregnancy.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102726"},"PeriodicalIF":5.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.coi.2025.102723
Ogugua N Obi , Elizabeth V Arkema , Yvette C Cozier
The incidence, prevalence, and burden of sarcoidosis is increasing worldwide. The Nordic countries have the highest incidence with lowest rates reported in Asia. In the United States, Black females have the highest incidence and prevalence of disease.
The phenotypic manifestations of sarcoidosis vary by race, age, gender, and geography. Historically, a female predominant pattern of disease occurrence has been widely reported, however, this is not a universal finding, and recent studies suggest an increasing incidence of disease in males. Though previously thought to be a disease of young adults, recent data shows the average age of diagnosis is now over 50 years with increasing incidence of disease reported in older adults (age >65 years).
Historical trends of disease occurrence, familial patterns and trends of disease presentation, environmental and seasonal clustering of disease, and recent trends in morbidity, co-morbidity, and mortality of sarcoidosis are discussed in this review.
{"title":"Patterns and trends in sarcoidosis: an epidemiological perspective","authors":"Ogugua N Obi , Elizabeth V Arkema , Yvette C Cozier","doi":"10.1016/j.coi.2025.102723","DOIUrl":"10.1016/j.coi.2025.102723","url":null,"abstract":"<div><div>The incidence, prevalence, and burden of sarcoidosis is increasing worldwide. The Nordic countries have the highest incidence with lowest rates reported in Asia. In the United States, Black females have the highest incidence and prevalence of disease.</div><div>The phenotypic manifestations of sarcoidosis vary by race, age, gender, and geography. Historically, a female predominant pattern of disease occurrence has been widely reported, however, this is not a universal finding, and recent studies suggest an increasing incidence of disease in males. Though previously thought to be a disease of young adults, recent data shows the average age of diagnosis is now over 50 years with increasing incidence of disease reported in older adults (age >65 years).</div><div>Historical trends of disease occurrence, familial patterns and trends of disease presentation, environmental and seasonal clustering of disease, and recent trends in morbidity, co-morbidity, and mortality of sarcoidosis are discussed in this review.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102723"},"PeriodicalIF":5.8,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.coi.2026.102724
Soumba Traore , Sophia C Chima , Kristina M Adams Waldorf , Jennifer Tisoncik-Go , Megan A O’Connor
As of 2024, the World Health Organization declared the Zika virus (ZIKV), an emerging flavivirus, as a high-priority pathogen with the potential to cause future Public Health Emergencies of International Concern. Although the last major outbreak of ZIKV occurred in 2015–2016, ongoing ‘silent’ transmission in the Americas, Asia, and Africa indicates that ZIKV remains a global threat. Recent research highlights possible reintroduction of ZIKV into sylvatic reservoirs, identifies mosquito immune cells essential for viral dissemination, uncovers viral protein mutations that affect neurovirulence, and examines how cross-reactive flavivirus immunity shapes disease outcomes. Despite these advances, major challenges persist in surveillance, diagnosis, and the development of effective vaccines or therapeutics. This review synthesizes current knowledge on the global burden of ZIKV, transmission dynamics, and adaptive evolution, emphasizing factors that drive its epidemic potential. Continued research and a One Health approach are crucial to improve understanding of ZIKV biology and strengthen preparedness for future outbreaks.
{"title":"Evaluating the pandemic potential of Zika virus in a changing global landscape","authors":"Soumba Traore , Sophia C Chima , Kristina M Adams Waldorf , Jennifer Tisoncik-Go , Megan A O’Connor","doi":"10.1016/j.coi.2026.102724","DOIUrl":"10.1016/j.coi.2026.102724","url":null,"abstract":"<div><div>As of 2024, the World Health Organization declared the Zika virus (ZIKV), an emerging flavivirus, as a high-priority pathogen with the potential to cause future Public Health Emergencies of International Concern. Although the last major outbreak of ZIKV occurred in 2015–2016, ongoing ‘silent’ transmission in the Americas, Asia, and Africa indicates that ZIKV remains a global threat. Recent research highlights possible reintroduction of ZIKV into sylvatic reservoirs, identifies mosquito immune cells essential for viral dissemination, uncovers viral protein mutations that affect neurovirulence, and examines how cross-reactive flavivirus immunity shapes disease outcomes. Despite these advances, major challenges persist in surveillance, diagnosis, and the development of effective vaccines or therapeutics. This review synthesizes current knowledge on the global burden of ZIKV, transmission dynamics, and adaptive evolution, emphasizing factors that drive its epidemic potential. Continued research and a One Health approach are crucial to improve understanding of ZIKV biology and strengthen preparedness for future outbreaks.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102724"},"PeriodicalIF":5.8,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.coi.2026.102725
Martha C Faraguna , Viola Crescitelli , Sonia Bonanomi , Gaia A Kullmann , Maria L Boffi , Roberta Pretese , Giulia Risca , Lucia M Tedesco , Katia Pozzi , Marta Serafini , Johanna MP van den Hout , Ans T van der Ploeg , Adriana C Balduzzi , Serena Gasperini
We report on 13 classic infantile Pompe patients, including four cross-reactive immunological material negative (31%), treated with alglucosidase alpha (rhGAA) at Fondazione IRCCS San Gerardo, Monza, between 2003 and 2024. Median age at rhGAA initiation was 3.3 months, with nine patients (69%) starting on doses > 20 mg/kg/every other week. With a median follow-up of 6.9 years, the 5- and 10-year survival was 92%. Four patients died, and three became ventilator-dependent. Hypertrophic cardiomyopathy normalized in all patients, though electrocardiogram abnormalities persisted in 36%. Walking was achieved by 10 (77%). Ten patients received immune tolerance induction (77%, five primary, two secondary, three both), and seven received long-term sirolimus. Nine developed anti-rhGAA, of whom five (38%) had high-sustained antibody titers (HSAT). All had elevated creatine kinase at diagnosis; creatine phosphokinase normalized over time in four patients on 40 mg/kg/week since start without HSAT. This study offers real-world insight into managing classic infantile Pompe disease and compares the cohort’s outcome to international experiences.
{"title":"A comprehensive study on the effect of alglucosidase alpha and immunomodulation on survival, motor and cardiac outcome, creatine kinase and antibody titers in classic infantile Pompe disease: the Monza experience","authors":"Martha C Faraguna , Viola Crescitelli , Sonia Bonanomi , Gaia A Kullmann , Maria L Boffi , Roberta Pretese , Giulia Risca , Lucia M Tedesco , Katia Pozzi , Marta Serafini , Johanna MP van den Hout , Ans T van der Ploeg , Adriana C Balduzzi , Serena Gasperini","doi":"10.1016/j.coi.2026.102725","DOIUrl":"10.1016/j.coi.2026.102725","url":null,"abstract":"<div><div>We report on 13 classic infantile Pompe patients, including four cross-reactive immunological material negative (31%), treated with alglucosidase alpha (rhGAA) at Fondazione IRCCS San Gerardo, Monza, between 2003 and 2024. Median age at rhGAA initiation was 3.3 months, with nine patients (69%) starting on doses > 20 mg/kg/every other week. With a median follow-up of 6.9 years, the 5- and 10-year survival was 92%. Four patients died, and three became ventilator-dependent. Hypertrophic cardiomyopathy normalized in all patients, though electrocardiogram abnormalities persisted in 36%. Walking was achieved by 10 (77%). Ten patients received immune tolerance induction (77%, five primary, two secondary, three both), and seven received long-term sirolimus. Nine developed anti-rhGAA, of whom five (38%) had high-sustained antibody titers (HSAT). All had elevated creatine kinase at diagnosis; creatine phosphokinase normalized over time in four patients on 40 mg/kg/week since start without HSAT. This study offers real-world insight into managing classic infantile Pompe disease and compares the cohort’s outcome to international experiences.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102725"},"PeriodicalIF":5.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.coi.2025.102720
Vivienne Kahlmann , Donald Simon , Marlies S Wijsenbeek , Catharina C Moor
Patients with sarcoidosis can present with a wide range of symptoms that impact their quality of life (QoL). QoL represents one of the most important treatment priorities for patients. Therefore, measuring what matters to patients is of great importance, though it can be challenging due to the diverse presentation of the disease. Patient-reported outcome measures (PROMs) are designed to assess patients’ subjective symptoms and their impact on their lives. Over the past decade, PROMS have been increasingly used in clinical trials and daily practice. In this review, we will provide an overview of frequently used generic- and disease-specific PROMS in the field op sarcoidosis. We summarize their psychometric properties and discuss limitations and future opportunities.
{"title":"Optimizing patient-reported outcomes for sarcoidosis","authors":"Vivienne Kahlmann , Donald Simon , Marlies S Wijsenbeek , Catharina C Moor","doi":"10.1016/j.coi.2025.102720","DOIUrl":"10.1016/j.coi.2025.102720","url":null,"abstract":"<div><div>Patients with sarcoidosis can present with a wide range of symptoms that impact their quality of life (QoL). QoL represents one of the most important treatment priorities for patients. Therefore, measuring what matters to patients is of great importance, though it can be challenging due to the diverse presentation of the disease. Patient-reported outcome measures (PROMs) are designed to assess patients’ subjective symptoms and their impact on their lives. Over the past decade, PROMS have been increasingly used in clinical trials and daily practice. In this review, we will provide an overview of frequently used generic- and disease-specific PROMS in the field op sarcoidosis. We summarize their psychometric properties and discuss limitations and future opportunities.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102720"},"PeriodicalIF":5.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.coi.2025.102722
Alaa Elsaghir , Torsten Witte
Primary Sjögren’s disease (SjD) is a systemic autoimmune disorder where diagnosis relies on the presence of Ro/SS-A and La/SS-B autoantibodies. However, approximately one-third of SjD patients are seronegative, often requiring an invasive minor salivary gland biopsy, which can lead to significant diagnostic delays. This review comprehensively evaluates a wide array of novel autoantibodies to determine their potential as diagnostic biomarkers for Ro/SS-A-negative SjD patients. While many newly identified autoantibodies, such as those targeting ASCA, TRIM38, and PUF60, were found to be strongly associated with Ro/SS-A positivity and thus offer limited utility for seronegative diagnosis, several others show significant promise.
Notably, autoantibodies targeting functional proteins like the muscarinic M3 receptor (anti-M3R) have demonstrated high diagnostic sensitivity and specificity. Furthermore, systematic screenings have uncovered highly specific markers. One panel of 12 autoantigens (including GMNN, GRAMD1A, and NUP50) identified by human proteome arrays exhibited 54% sensitivity with 100% specificity for Ro/SS-A-negative SjD. Another validated panel combining immunoglobulin G autoantibodies against FNBP4, SNRPC, CCL4, M3R, and KDM6B achieved 46% sensitivity with 95% specificity. Other individual markers, such as anti-NA14 and anti-calponin-3, also show potential for identifying seronegative SjD subsets.
In conclusion, a growing body of evidence supports the clinical utility of several novel autoantibodies in diagnosing Ro/SS-A-negative SjD. The integration of these biomarkers into clinical practice could significantly improve early and accurate diagnosis, reduce the reliance on invasive procedures, and potentially aid in patient stratification for targeted therapies. Further validation of these markers in large cohorts is warranted.
原发性Sjögren病（SjD）是一种系统性自身免疫性疾病，其诊断依赖于Ro/SS-A和La/SS-B自身抗体的存在。然而，大约三分之一的SjD患者血清阴性，通常需要进行侵入性小唾液腺活检，这可能导致严重的诊断延迟。这篇综述全面评估了一系列新的自身抗体，以确定它们作为Ro/ ss - a阴性SjD患者的诊断生物标志物的潜力。虽然许多新发现的自身抗体，如靶向ASCA、TRIM38和PUF60的抗体，被发现与Ro/SS-A阳性密切相关，因此对血清阴性诊断的效用有限，但其他一些抗体显示出很大的希望。值得注意的是，针对功能蛋白（如muscarinic M3受体（anti-M3R））的自身抗体已显示出较高的诊断敏感性和特异性。此外，系统筛选发现了高度特异性的标记。人类蛋白质组阵列鉴定的一组12种自身抗原（包括GMNN、GRAMD1A和NUP50）对Ro/ ss - a阴性SjD的敏感性为54%，特异性为100%。另一个经验证的小组结合了针对FNBP4、SNRPC、CCL4、M3R和KDM6B的免疫球蛋白G自身抗体，灵敏度为46%，特异性为95%。其他个体标记物，如抗na14和抗钙钙蛋白-3，也显示出识别血清阴性SjD亚群的潜力。总之，越来越多的证据支持几种新型自身抗体在诊断Ro/ ss - a阴性SjD中的临床应用。将这些生物标志物整合到临床实践中可以显著提高早期和准确的诊断，减少对侵入性手术的依赖，并可能有助于患者分层进行靶向治疗。这些标记物在大型队列中的进一步验证是有必要的。
{"title":"New autoantibodies in Sjögren's disease","authors":"Alaa Elsaghir , Torsten Witte","doi":"10.1016/j.coi.2025.102722","DOIUrl":"10.1016/j.coi.2025.102722","url":null,"abstract":"<div><div>Primary Sjögren’s disease (SjD) is a systemic autoimmune disorder where diagnosis relies on the presence of Ro/SS-A and La/SS-B autoantibodies. However, approximately one-third of SjD patients are seronegative, often requiring an invasive minor salivary gland biopsy, which can lead to significant diagnostic delays. This review comprehensively evaluates a wide array of novel autoantibodies to determine their potential as diagnostic biomarkers for Ro/SS-A-negative SjD patients. While many newly identified autoantibodies, such as those targeting ASCA, TRIM38, and PUF60, were found to be strongly associated with Ro/SS-A positivity and thus offer limited utility for seronegative diagnosis, several others show significant promise.</div><div>Notably, autoantibodies targeting functional proteins like the muscarinic M3 receptor (anti-M3R) have demonstrated high diagnostic sensitivity and specificity. Furthermore, systematic screenings have uncovered highly specific markers. One panel of 12 autoantigens (including GMNN, GRAMD1A, and NUP50) identified by human proteome arrays exhibited 54% sensitivity with 100% specificity for Ro/SS-A-negative SjD. Another validated panel combining immunoglobulin G autoantibodies against FNBP4, SNRPC, CCL4, M3R, and KDM6B achieved 46% sensitivity with 95% specificity. Other individual markers, such as anti-NA14 and anti-calponin-3, also show potential for identifying seronegative SjD subsets.</div><div>In conclusion, a growing body of evidence supports the clinical utility of several novel autoantibodies in diagnosing Ro/SS-A-negative SjD. The integration of these biomarkers into clinical practice could significantly improve early and accurate diagnosis, reduce the reliance on invasive procedures, and potentially aid in patient stratification for targeted therapies. Further validation of these markers in large cohorts is warranted.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102722"},"PeriodicalIF":5.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.coi.2025.102719
Yohei Kirino , Mitsuhiro Takeno
Autoinflammatory diseases (AIDs) comprise a diverse group of conditions arising from dysregulated immune control due to congenital or acquired genetic abnormalities in innate immune pathways, and patients typically require lifelong treatment. Owing to their rarity, access to patient samples is limited, making animal and cellular models indispensable for elucidating pathogenesis and advancing therapeutic development. Nevertheless, robust animal and cell-based models remain scarce. Recent advances in precision genome editing now enable lineage- and cell type-specific modeling of autoinflammation, steadily improving the fidelity with which disease phenotypes are recapitulated. In this review, we survey the current landscape of CRISPR-enabled knock-in/knock-out animal models, engineered cell lines, and patient-derived induced pluripotent stem cells for AIDs, and discuss how these platforms can be leveraged to dissect disease mechanisms and accelerate drug discovery.
{"title":"A critical look at animal and cellular models in autoinflammatory diseases","authors":"Yohei Kirino , Mitsuhiro Takeno","doi":"10.1016/j.coi.2025.102719","DOIUrl":"10.1016/j.coi.2025.102719","url":null,"abstract":"<div><div>Autoinflammatory diseases (AIDs) comprise a diverse group of conditions arising from dysregulated immune control due to congenital or acquired genetic abnormalities in innate immune pathways, and patients typically require lifelong treatment. Owing to their rarity, access to patient samples is limited, making animal and cellular models indispensable for elucidating pathogenesis and advancing therapeutic development. Nevertheless, robust animal and cell-based models remain scarce. Recent advances in precision genome editing now enable lineage- and cell type-specific modeling of autoinflammation, steadily improving the fidelity with which disease phenotypes are recapitulated. In this review, we survey the current landscape of CRISPR-enabled knock-in/knock-out animal models, engineered cell lines, and patient-derived induced pluripotent stem cells for AIDs, and discuss how these platforms can be leveraged to dissect disease mechanisms and accelerate drug discovery.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102719"},"PeriodicalIF":5.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.coi.2025.102721
Shiliang Ma , Xinran Wu , Xuan Zhang, Ketian Li
Elderly-onset rheumatoid arthritis (EORA), defined as onset at ≥60 years, is a clinically distinct and increasingly prevalent subset of rheumatoid arthritis (RA). This review synthesizes evidence that EORA is not merely late-onset RA but a pathogenically unique entity, driven by immune aging, inflammaging, and other mechanisms like defective immunosuppressive system, age-related somatic mosaicism, and dysbiosis. It frequently presents with heterogeneous features such as acute large-joint involvement and polymyalgia symptoms, often leading to diagnostic delays. Despite similar initial activity to young-onset RA, EORA follows a more aggressive course with severe joint destruction and significant comorbidities. Treatment with conventional disease-modifying antirheumatic drugs is complicated by polypharmacy and high adverse event risks, often leading to undertreatment. A shift to geriatric-centered care, with comprehensive assessment and tailored treat-to-target strategies, is therefore imperative. This review underscores the need to recognize EORA's unique pathophysiology and clinical profile to improve diagnosis, therapy, and outcomes for this growing population.
{"title":"Elderly-onset rheumatoid arthritis as a distinct entity: mechanisms, manifestations, and treatment","authors":"Shiliang Ma , Xinran Wu , Xuan Zhang, Ketian Li","doi":"10.1016/j.coi.2025.102721","DOIUrl":"10.1016/j.coi.2025.102721","url":null,"abstract":"<div><div>Elderly-onset rheumatoid arthritis (EORA), defined as onset at ≥60 years, is a clinically distinct and increasingly prevalent subset of rheumatoid arthritis (RA). This review synthesizes evidence that EORA is not merely late-onset RA but a pathogenically unique entity, driven by immune aging, inflammaging, and other mechanisms like defective immunosuppressive system, age-related somatic mosaicism, and dysbiosis. It frequently presents with heterogeneous features such as acute large-joint involvement and polymyalgia symptoms, often leading to diagnostic delays. Despite similar initial activity to young-onset RA, EORA follows a more aggressive course with severe joint destruction and significant comorbidities. Treatment with conventional disease-modifying antirheumatic drugs is complicated by polypharmacy and high adverse event risks, often leading to undertreatment. A shift to geriatric-centered care, with comprehensive assessment and tailored treat-to-target strategies, is therefore imperative. This review underscores the need to recognize EORA's unique pathophysiology and clinical profile to improve diagnosis, therapy, and outcomes for this growing population.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102721"},"PeriodicalIF":5.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating granulomas in various organs, predominantly affecting the lungs and lymphatic system. Although the etiology of sarcoidosis remains unknown, it is believed to result from an abnormal immune response triggered by environmental agents in a genetically susceptible host. The disease also has a variation in clinical outcome, with some patients spontaneously resolving their disease, while others experience disease progression. Pulmonary sarcoidosis, the most prevalent form, can progressively lead to pulmonary fibrosis, which may result in organ impairment and respiratory failure. Cellular metabolism has been implicated in numerous chronic lung diseases, making the characterization of metabolic profiles a promising approach for prognosis. A limited number of studies have examined the metabolomic profiles of sarcoidosis patients to identify key metabolites that contribute to disease progression. This review will focus on the current state of metabolomics in understanding sarcoidosis pathogenesis.
{"title":"Metabolomic signaling in sarcoidosis pathogenesis","authors":"Humphrey Lotana, Tristan White, Wonder Puryear Drake","doi":"10.1016/j.coi.2025.102715","DOIUrl":"10.1016/j.coi.2025.102715","url":null,"abstract":"<div><div>Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating granulomas in various organs, predominantly affecting the lungs and lymphatic system. Although the etiology of sarcoidosis remains unknown, it is believed to result from an abnormal immune response triggered by environmental agents in a genetically susceptible host. The disease also has a variation in clinical outcome, with some patients spontaneously resolving their disease, while others experience disease progression. Pulmonary sarcoidosis, the most prevalent form, can progressively lead to pulmonary fibrosis, which may result in organ impairment and respiratory failure. Cellular metabolism has been implicated in numerous chronic lung diseases, making the characterization of metabolic profiles a promising approach for prognosis. A limited number of studies have examined the metabolomic profiles of sarcoidosis patients to identify key metabolites that contribute to disease progression. This review will focus on the current state of metabolomics in understanding sarcoidosis pathogenesis.</div></div>","PeriodicalId":11361,"journal":{"name":"Current Opinion in Immunology","volume":"99 ","pages":"Article 102715"},"PeriodicalIF":5.8,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.coi.2025.102714
Valeria Manfrè , Luca Quartuccio , Sara S McCoy
Sjögren’s disease (SjD) is a systemic, heterogeneous autoimmune disorder, clinically dominated by dryness symptoms resulting from inflammatory infiltration of exocrine glands. To date, no validated and resolutive therapeutic strategies are available. Stromal cells are increasingly recognized as critical players in SjD pathogenesis. Distinct fibroblast subsets, termed ‘immunofibroblasts’, may contribute to tertiary lymphoid structure development and fibrotic tissue remodeling, while sustaining local immune infiltration, thereby representing potential treatment targets. In parallel, mesenchymal stromal cells (MSCs) may represent a therapeutic tool, due to their immunomodulatory and trophic properties demonstrated in vitro and in animal models. These favorable results have prompted early-phase clinical trials using MSCs, which demonstrated preliminary safety and efficacy on salivary and ocular outcomes. Nonetheless, methodological limitations require cautious interpretation of available data, and further investigation of clinical applications is warranted. Stromal cell biology thus offers both mechanistic insight and therapeutic promise, warranting further investigation in rigorously designed randomized controlled trials.
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