Journal of Internal Medicine最新文献

{"title":"Association of histologic and clinical activity with major adverse cardiovascular events in patients with inflammatory bowel disease: A cohort study.","authors":"Jiangwei Sun, Karl Mårild, Johan Sundström, David Bergman, Fahim Ebrahimi, Jonas Halfvarson, Ola Olén, Jonas F Ludvigsson","doi":"10.1111/joim.70035","DOIUrl":"https://doi.org/10.1111/joim.70035","url":null,"abstract":"<p><strong>Objectives: </strong>Inflammatory bowel disease (IBD) is a chronic disorder linked to cardiovascular disease (CVD). However, the impact of histologic and clinical activity on this association remains unclear.</p><p><strong>Methods: </strong>We conducted a nationwide cohort study in Sweden involving 59,168 IBD patients diagnosed in 1969-2017 with histologic evaluation and 91,800 patients diagnosed in 1969-2020 with assessment of clinical activity in 2006-2021. The primary outcome was incident major adverse cardiovascular events (MACE), a composite outcome encompassing ischemic heart disease, stroke, and heart failure. Cox proportional hazards model estimated adjusted hazard ratios (aHRs) of MACE and its subcomponents.</p><p><strong>Results: </strong>We found an increased MACE risk following histologic inflammation (n = 868, incidence rate [IR]: 86.3/10,000 person-years) compared to remission (n = 558, IR = 71.3) (aHR = 1.16 [1.04-1.30]). This excess risk was evident in Crohn's disease (aHR = 1.30 [1.03-1.64]) and ulcerative colitis (aHR = 1.13 [1.01-1.27]). Histologic inflammation was associated with an increased risk of ischemic heart disease, myocardial infarction, ischemic stroke, and heart failure, but not with hemorrhagic stroke. Compared to clinically quiescent IBD, active IBD was associated with an increased MACE risk (IR: 131.4 vs. 93.7; aHR = 1.54 [1.46-1.63]) and all MACE subcomponents. In patients with clinically quiescent IBD, histologic inflammation remained linked to myocardial infarction (aHR = 1.29 [1.06-1.58]) and heart failure (aHR = 1.19 [1.00-1.43]).</p><p><strong>Conclusion: </strong>Both histologic and clinical activities of IBD were associated with an increased MACE risk, suggesting that improved disease control may reduce MACE risk in IBD.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353292","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}

{"title":"Trends, timing, and predictors of alcohol use disorder treatment among US adult cancer survivors.","authors":"Jyun-Heng Lai, Anton L V Avanceña, Minh H K Nguyen, Corwin M Zigler, Mary M Velasquez, Christopher R Frei, Michael Pignone","doi":"10.1111/joim.70033","DOIUrl":"https://doi.org/10.1111/joim.70033","url":null,"abstract":"<p><strong>Background: </strong>Little is known about the initiation of alcohol use disorder (AUD) treatments among cancer survivors, despite the unique harms that unhealthy alcohol use may have on this population. We assessed patterns, timing, and predictors of AUD treatment among cancer survivors.</p><p><strong>Methods: </strong>We used commercial claims data on US adult cancer survivors from 2011 to 2021 in this retrospective cohort study. We included individuals with a new AUD diagnosis and continuous insurance enrollment. We measured initiation and timing of Food and Drug Administration (FDA)-approved (naltrexone, acamprosate, and disulfiram), non-FDA-approved (gabapentin, topiramate, and baclofen), and investigational (ondansetron and varenicline) medications for AUD (MAUDs), psychosocial therapies, and rehabilitation for AUD. We employed survival analysis to identify sociodemographic and clinical predictors of time to AUD treatment initiation.</p><p><strong>Results: </strong>Among 6,682,292 cancer survivors, 44,081 individuals newly diagnosed with AUD met the inclusion criteria. Of these, 14.7% initiated FDA-approved MAUDs (3.0%), psychosocial therapy (13.0%), or both (1.3%). The median time to initiate FDA-approved MAUD or psychosocial therapy was 28 days. Overall, 6.3% and 10.4% of cancer survivors, respectively, initiated non-FDA-approved and investigational MAUDs. Age, use of antineoplastic agents, mental disorders, and comorbidity severity are potential determinants with varying effects on AUD treatment initiation.</p><p><strong>Conclusion: </strong>Less than 15% of cancer survivors initiated recommended MAUDs or psychosocial therapy in the year following their new AUD diagnoses, and those who did initiate treatment did so nearly a month after receiving AUD diagnoses. Interventions are warranted to enhance treatment initiation among cancer survivors with AUD to reduce alcohol-related harms.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353227","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}

{"title":"Statin use for primary prevention of cardiovascular disease reduces the risk of incident IBD: A population-based cohort study.","authors":"Adam S Faye, Kristine H Allin, Gry Juul Poulsen, Tine Jess","doi":"10.1111/joim.70034","DOIUrl":"https://doi.org/10.1111/joim.70034","url":null,"abstract":"<p><strong>Background and objectives: </strong>Beyond genetics, environmental factors may contribute to the rising incidence of inflammatory bowel disease (IBD). Statins, widely used for cardiovascular risk reduction, also have anti-inflammatory properties and have been hypothesized to reduce IBD risk, though data are limited. We prospectively assessed the association between statin use and risk of developing IBD among individuals eligible for statin therapy for primary prevention of cardiovascular disease.</p><p><strong>Methods: </strong>Using a prospective new user design within the Danish National Registries, we identified a nationwide cohort of individuals aged ≥40 years from 2008 to 2022 eligible for statin therapy for primary cardiovascular prevention. Statin users were matched 1:5 to nonusers on age, sex, calendar year, and cardiovascular risk factors. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for incident IBD.</p><p><strong>Results: </strong>We identified 110,961 statin users and 554,805 matched nonusers. Statin use was associated with a reduced risk of IBD (aHR 0.84, 95% CI 0.72-0.97), with subgroup analyses showing similar reductions for Crohn's disease (aHR 0.84, 95% CI 0.65-1.09) and ulcerative colitis (aHR 0.83, 95% CI 0.69-1.00). This corresponds to a number needed to treat of 2881 to prevent one additional IBD case over 5 years of statin treatment. Findings remained consistent when censoring individuals at statin discontinuation.</p><p><strong>Conclusion: </strong>In this nationwide prospective study, statin use among individuals eligible for primary cardiovascular prevention was associated with a lower risk of developing IBD. These findings suggest a potential additional benefit of statins and support further research into their role in IBD prevention.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353281","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}

{"title":"Ignoring the planet: A critical blind spot for research on ageing.","authors":"Shiels Pg, Neytchev O, Borland G, Gremushkina P, Johnson Rj, Stenvinkel P, Woods T","doi":"10.1111/joim.70032","DOIUrl":"https://doi.org/10.1111/joim.70032","url":null,"abstract":"<p><p>Although research on ageing has largely concentrated on understanding the fundamental biology of the ageing process and devising pharmaceutical interventions in order to slow it down, increasing evidence has underscored the crucial role of environmental inputs across the life course and across generations, in shaping both individual and intergenerational trajectories of age-related health. These include nutrition, air pollution, social deprivation, lifestyle factors, climate change and exposure to environmental toxins, including microplastics and nanoplastics. The development of the concept of the exposome of ageing and the emergence of the new field of 'exposomics' have identified a blind spot, in particular, for geroscience. The impact of the exposome affecting human 'healthspan' (i.e., years lived in good health), extending across generations, is significant and yet under-explored in research. As such, it is under-appreciated that the declining health of the planet will have intergenerational ripple effects, epigenetically priming adverse health in future generations. We discuss the capacity to manipulate our exposome to mitigate against such effects, by addressing root causes, rather than symptoms, of both physiological and planetary dysregulation, dysfunction and decay. We propose a systems-based framework that reconnects research on ageing with exposomics and planetary ecology, creating a new field of 'ecological or exposome pharmacology', harnessing the activity of Nrf2 as a senotherapeutic intervention to improve trans- and intergenerational physiology in the face of declining planetary health.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342327","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}

{"title":"High cholesterol absorption efficiency interferes with bile acid metabolism and cholesterol elimination from the body.","authors":"Piia Simonen, Ingmar Wester, Jyri Lommi, Juha Sinisalo, Helena Gylling","doi":"10.1111/joim.70031","DOIUrl":"https://doi.org/10.1111/joim.70031","url":null,"abstract":"<p><strong>Background: </strong>Elevated low-density lipoprotein (LDL) cholesterol causes atherosclerotic cardiovascular diseases. Variables of whole-body cholesterol metabolism, for example, high cholesterol absorption efficiency, might also be atherogenic, whereas the role of bile acids is controversial.</p><p><strong>Objectives: </strong>This post hoc study concerns the impact of cholesterol absorption on bile acid metabolism. The hypothesis was that cholesterol absorption efficiency interferes with bile acid metabolism.</p><p><strong>Methods: </strong>Cholesterol metabolism was studied using absolute and relative methods. Elimination of cholesterol from the body as bile acids and neutral sterols was assessed from 24-h faecal collections and analysed by gas-liquid chromatography. Cholesterol absorption efficiency was evaluated by a peroral continuous dual-isotope feeding method, and cholesterol synthesis by a sterol-balance technique. The relative methods included analyses of serum biomarkers of cholesterol absorption efficiency and cholesterol synthesis by gas-liquid chromatography.</p><p><strong>Results: </strong>Faecal bile acids, neutral sterols and cholesterol synthesis were lower in high- versus low-cholesterol absorbers. Elimination of cholesterol from the body as bile acids and neutral sterols was reduced in high- versus low-cholesterol absorbers. Serum and LDL cholesterol levels did not differ in low- versus high-cholesterol absorbers. Absolute and relative methods of cholesterol metabolism correlated with each other, suggesting that the results can be considered valid.</p><p><strong>Conclusion: </strong>In high-cholesterol absorbers, poor elimination of cholesterol from the body as bile acids and neutral sterols may indicate an increased risk of atherosclerosis. It can be prevented by decreasing cholesterol absorption and increasing reverse cholesterol transport by dietary means combined with ezetimibe and statin treatment, when needed.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335963","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}

{"title":"Systemic neutrophil activation and N-formyl methionine-formyl peptide receptor-1 signaling define inflammatory endotypes in rheumatoid arthritis-associated lung involvement.","authors":"Jia Shi, Chen Yu, Dan Ke, Xueting Yuan, Yiyun Pang, Yang Wu, Ting Wang, Ryan Stultz, Xiaomin Liu, Xinping Tian, Mengtao Li, Qian Wang, M Kristen Demoruelle, Joshua J Solomon, Christian Lood","doi":"10.1111/joim.70030","DOIUrl":"https://doi.org/10.1111/joim.70030","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil activation plays a crucial role in the pathogenesis of rheumatoid arthritis (RA), but its involvement in RA-associated interstitial lung disease (RA-ILD) remains unclear. This study investigated the involvement of N-formyl methionine (fMET) and its receptor formyl peptide receptor-1 (FPR1) in neutrophil-mediated inflammation in RA-ILD.</p><p><strong>Methods: </strong>Plasma and sputum levels of fMET and neutrophil activation markers were measured by ELISA in two cohorts (n = 269 and 314) spanning multiple disease subgroups. Neutrophil activation was assessed by flow cytometry following plasma stimulation, with or without FPR1 inhibitors.</p><p><strong>Results: </strong>Calprotectin levels were significantly elevated in both plasma and sputum of RA-ILD patients compared to controls and RA-noILD patients (p < 0.05 for all analyses) and were negatively correlated with pulmonary function in RA (forced vital capacity [FVC], r = -0.39, p = 0.0002; diffusing capacity for carbon monoxide [DLCO], r = -0.39, p = 0.001). Plasma fMET levels were higher in RA-ILD patients compared to healthy controls (p < 0.0001) as well as compared to RA-noILD patients (p < 0.01), with a significant inverse correlation to pulmonary function in RA patients (FVC, r = -0.42, p < 0.0001; DLCO, r = -0.31, p = 0.01). Plasma from RA-ILD patients induced neutrophil activation through FPR1-dependent mechanisms (p < 0.0001). Hierarchical clustering identified reproducible subgroups defined by fMET and calprotectin, with the high-fMET cluster enriched for RA-ILD and associated with lower DLCO (p < 0.05).</p><p><strong>Conclusions: </strong>The fMET-FPR1 axis is associated with neutrophil activation in RA-ILD and defines inflammatory endotypes associated with lung impairment. Neutrophil-based biomarkers may enable early risk stratification and provide rationale for targeting the fMET-FPR1 axis in RA-ILD.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290481","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}

{"title":"Coexisting inflammatory bowel disease in primary sclerosing cholangitis is associated with higher colorectal cancer and transplant risk.","authors":"Chengu Niu, Jing Zhang, Prajjwol Bhatta, Kaiwen Zhu, Nagesh Jadhav, Patrick I Okolo, Asim Mushtaq, Ebubekir Daglilar","doi":"10.1111/joim.70026","DOIUrl":"https://doi.org/10.1111/joim.70026","url":null,"abstract":"<p><strong>Background: </strong>Primary sclerosing cholangitis (PSC) is often intertwined with inflammatory bowel disease (IBD), presenting a complex clinical scenario. The coexistence of IBD-PSC complicates disease management and progression, potentially exacerbating outcomes.</p><p><strong>Objectives: </strong>This study aims to evaluate the specific impact of IBD in patients with PSC, focusing on both liver-related and IBD-specific clinical outcomes.</p><p><strong>Methods: </strong>This retrospective study, utilizing the TriNetX database, performed propensity score matching to compare clinical outcomes between IBD-PSC and PSC-only patients, as well as IBD-PSC and IBD-only patients. Diagnoses were identified based on International Classification of Diseases-10 coding.</p><p><strong>Results: </strong>The study analyzed 1941 patients with IBD-PSC, 234,081 with IBD alone, and 628 with PSC alone. Patients with IBD-PSC had significantly higher mortality compared to IBD alone (16.0% vs. 7.5%; hazard ratio [HR]: 2.256, 95% confidence interval [CI]: 1.853-2.747, p < 0.001), as well as increased rates of hospitalization (32.8% vs. 14.5%; HR: 2.641, 95% CI: 2.213-3.152, p < 0.001) and intensive care unit admission (18.7% vs. 5.8%; HR: 3.691, 95% CI: 2.954-4.612, p < 0.001). Colorectal cancer was also more frequent in the IBD-PSC group (2.4% vs. 0.7%; HR: 3.370, 95% CI: 1.846-6.152, p < 0.001). When compared to PSC alone, IBD-PSC patients had a higher rate of liver transplantation (12.3% vs. 8.0%; HR: 1.492, 95% CI: 1.012-2.198, p = 0.042), whereas rates of hepatocellular carcinoma and cholangiocarcinoma were similar between groups.</p><p><strong>Conclusions: </strong>Patients with coexisting IBD and PSC experience greater clinical severity, including higher mortality, hospitalization, and colorectal cancer risk. They also have increased liver transplant incidence. Further research is needed to explore underlying mechanisms and improve management.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290454","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}

{"title":"Health inequalities in the Nordic countries: A comparative overview and update.","authors":"Johan Fritzell, Stefan Fors","doi":"10.1111/joim.70029","DOIUrl":"https://doi.org/10.1111/joim.70029","url":null,"abstract":"<p><p>In this article, we present the state-of-the-art on socioeconomic health inequalities with a focus on the Nordic countries. Health inequalities have increased over time and can be observed for both mortality and morbidity. We show that cross-national comparisons reveal surprisingly high inequalities in the Nordic countries. It is now well established that health and mortality inequalities prevail also at older ages. We show, with data from Sweden, that the interpretation of how mortality inequalities evolve over the life course is markedly different depending on whether we focus on absolute or relative inequalities. Although there is a consensus on basic descriptive facts, disagreements on how these facts are best explained and why they persist and even increase remain. We present a general discussion on how to explain health inequalities, as well as a discussion on why patterns may differ between European regions and across the life course. We introduce a framework for understanding health inequalities, fundamental cause theory and discuss to what extent the evidence aligns with the theory. We review contemporary discussions on health inequalities in light of recent evidence based on novel methods for causal inference. We argue that health inequalities have important ramifications for population health regardless of whether they are primarily shaped by social causation or social selection and end by noting that as modern societies aspire to become more meritocratic, it is possible that socioeconomic position becomes increasingly important for health.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273248","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}

{"title":"CD71⁺ erythroid cell expansion in late-onset systemic lupus erythematosus.","authors":"Jian Hao, Yuechen Cui, Jun Du, Jing Cui, Hui-Qi Qu, Fumin Qi, Hui Wang, Na Zhang, Jin Li, Wei Wei","doi":"10.1111/joim.70027","DOIUrl":"https://doi.org/10.1111/joim.70027","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) mainly affects women of reproductive age. Late-onset SLE patients (lo-SLE, ≥50 years) are generally indolent and have less severe manifestations.</p><p><strong>Objective: </strong>The present study aims to decode molecular differences underlying the distinct clinical presentations between lo-SLE and early onset SLE patients.</p><p><strong>Methods: </strong>In a cohort of 243 treatment-naïve Chinese SLE female patients, we carried out clinical analysis and experimental validation studies. RNA-seq was used to identify differentially expressed genes (DEGs) of lo-SLE patients. Reverse transcription quantitative polymerase chain reaction and flow cytometry were utilized to validate DEGs and enriched cell types. The discovery was further compared to findings in a European cohort. The immunosuppressive function of CD71⁺CD235a⁺ erythroid cells (CECs) was evaluated by coculturing peripheral blood mononuclear cells (PBMCs) with CECs.</p><p><strong>Results: </strong>Differential expression analysis identified a group of hub upregulated genes in lo-SLE patients. These genes, overrepresented in erythrocyte differentiation, are highly enriched in CECs. In our Chinese cohort, CECs abundance in peripheral blood was inversely correlated with disease activity. Increased CECs in treatment-naïve lo-SLE patients may play an immunosuppressive role by inhibiting CD8⁺ T cell function and IFN-γ production. This immunosuppressive role was evidenced by the significant suppression of IL-6, IFN-γ, and IL-17A production by healthy donor's PBMCs cocultured with SLE bone marrow-derived CECs.</p><p><strong>Conclusions: </strong>This pioneering study has revealed a panel of CECs genes as potential molecular markers for lo-SLE, supporting a novel erythroid modulation theory. These novel findings provide valuable insights into previously unrecognized molecular mechanisms underlying the latent disease activity of lo-SLE.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237424","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}

{"title":"Low positive and borderline negative transglutaminase antibody levels are frequently associated with a coeliac disease diagnosis.","authors":"Rakel Nurmi, Celina Turunen Beteta, Kalle Kurppa, Heini Huhtala, Katri Lindfors, Laura Kivelä, Katri Kaukinen, Saana Paavola","doi":"10.1111/joim.70025","DOIUrl":"https://doi.org/10.1111/joim.70025","url":null,"abstract":"<p><strong>Background: </strong>Due to the expanding screening of coeliac disease (CeD), low positive and borderline negative serum transglutaminase 2 antibody (TGA) values are causing increasing confusion in clinical practice.</p><p><strong>Objectives: </strong>To investigate the significance of these findings in a well-defined patient cohort.</p><p><strong>Methods: </strong>Altogether 311 IgA-competent adults, with clinical suspicion or family history of CeD, underwent duodenal sampling and testing for TGA (ImmunoCAP EliA, cut-off 7.0 U/mL) and endomysial antibodies (EmA). TGA values 7.0-14.0 U/mL were defined as low positive and 3.0-6.9 U/mL as borderline negative. Besides conventional histology, small bowel mucosal TGA-targeted IgA deposits and γδ+ intraepithelial lymphocytes (IELs) were determined as CeD-specific markers.</p><p><strong>Results: </strong>Twenty-eight (9%) individuals had low positive TGA, and 22 (79%) were also positive for EmA. Among those with low positive TGA, all EmA positive and 50% of the EmA negative subjects were diagnosed with CeD. Thirty-nine individuals (13%) had borderline negative TGA, and 36% were positive for EmA. Of these, 79% of EmA positive and 12% of EmA negative subjects were diagnosed with CeD. Additionally, 29% of the subjects with borderline negative TGA and no diagnosis exhibited signs of incipient CeD, including positive IgA deposits, increased density of γδ+ IELs and presence of human leukocyte antigen DQ2/DQ8. All subjects with TGA ≥ 3.2× upper limit of normal (22.4 U/mL) received a CeD diagnosis.</p><p><strong>Conclusion: </strong>Low positive and borderline negative TGA frequently implies a CeD diagnosis, particularly in EmA positive individuals, or at least may be an indicator of an early stage of the disease.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136019","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}