Clinical immunology最新文献_第10页

Genetic variability associates with ancestry, age at disease onset, organ involvement and disease severity in juvenile-onset systemic lupus erythematosus 遗传变异与祖先、发病年龄、器官受累和青少年系统性红斑狼疮的疾病严重程度有关。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-15 DOI: 10.1016/j.clim.2025.110540

Valentina Natoli , Amandine Charras , Megan S.R. Hasoon , Andrea L. Jorgensen , Eve M.D. Smith , Eva Caamaño Gutiérrez , Michael W. Beresford , Christian M. Hedrich

Juvenile-onset systemic lupus erythematosus (jSLE) is a complex autoimmune/inflammatory disease in which genetic factors likely contribute to pathophysiology and clinical expression. This study explored associations between general (alternate allele counts; AAC) and gene-specific (alternate allele scores; GAAS) sequence variability, age at onset, sex, ancestry, disease activity/severity, organ involvement and treatments in jSLE. 289 participants from the UK JSLE Cohort Study underwent panel sequencing of 62 genes/genomic regions. Weighted AAC and GAAS were calculated. Correlation analyses and generalized linear models assessed associations between genetic burden, ancestry, age at diagnosis and clinical variables. AAC inversely correlated with age at diagnosis (R = -0.15, p = 0.01), primarily driven by South Asians (R = -0.28, p < 0.001). African/Caribbean patients exhibited higher AAC (p < 0.001). Clinical variables, including severity of renal involvement (ACP5, ITGAM, LYN, p < 0.001; TNFAIP3, p = 0.007), associated with GAAS. Genetic variability likely contributes to early disease expression and severity in jSLE, supporting patient stratification and personalised care.

青少年系统性红斑狼疮（jSLE）是一种复杂的自身免疫/炎症性疾病，遗传因素可能参与病理生理和临床表现。本研究探讨了一般（交替）等位基因数量；AAC)和基因特异性(交替等位基因得分；GAAS)序列变异性、发病年龄、性别、血统、疾病活动性/严重程度、器官受累和jSLE的治疗。来自英国JSLE队列研究的289名参与者对62个基因/基因组区域进行了面板测序。计算加权AAC和GAAS。相关分析和广义线性模型评估了遗传负担、血统、诊断年龄和临床变量之间的关联。AAC与诊断年龄呈负相关（R = -0.15,p = 0.01），主要由南亚人驱动(R = -0.28,p

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引用次数: 0

The role of immune cells glycolysis in neuroinflammation secondary to intracerebral hemorrhage 免疫细胞糖酵解在脑出血继发神经炎症中的作用

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-14 DOI: 10.1016/j.clim.2025.110543

Baochun Luo , Sifan Liu , Lei Zheng , Baiwen Zhang , Yaxin Shang , Tong Shang , Jia Zheng , Binglin Kuang , Wei Zou

Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, making the effective prevention and treatment of inflammatory secondary injury crucial. Recently, the role of immune cell metabolism in ICH has gained attention, particularly the regulatory mechanisms of glycolytic reprogramming in neuroinflammation. This review explores how glycolysis activation in peripheral immune cells (including neutrophils, macrophages, T cells, and natural killer cells), central immune cells (microglia), and other glial cells (including astrocytes and oligodendrocytes) involved in immune regulation influences the inflammatory response following ICH. We analyze the metabolic shifts in glycolysis within these immune cells, highlighting its dual role in neuroinflammation: glycolysis not only provides rapid energy to immune cells, which can either promote or inhibit inflammation, but lactate—a glycolysis byproduct—can modulate inflammatory damage by altering pH and immune cell function. Furthermore, we explore the therapeutic potential of targeting glycolysis in immune cells for neuroinflammation treatment. A deeper understanding of the glycolytic mechanism in ICH may facilitate the development of clinical therapeutic strategies targeting metabolism.

脑出血是脑卒中最致命的亚型，因此有效预防和治疗炎症性继发性损伤至关重要。近年来，免疫细胞代谢在脑出血中的作用引起了人们的关注，特别是糖酵解重编程在神经炎症中的调节机制。本文综述了参与免疫调节的外周免疫细胞（包括中性粒细胞、巨噬细胞、T细胞和自然杀伤细胞）、中枢免疫细胞（小胶质细胞）和其他胶质细胞（包括星形胶质细胞和少突胶质细胞）的糖酵解激活如何影响脑出血后的炎症反应。我们分析了这些免疫细胞中糖酵解的代谢变化，强调了它在神经炎症中的双重作用：糖酵解不仅为免疫细胞提供快速能量，可以促进或抑制炎症，而且乳酸-糖酵解的副产物-可以通过改变pH值和免疫细胞功能来调节炎症损伤。此外，我们探索靶向免疫细胞糖酵解治疗神经炎症的治疗潜力。对脑出血中糖酵解机制的深入了解可能有助于开发针对代谢的临床治疗策略。

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引用次数: 0

IKZF1: An important target for the treatment of autoimmune diseases IKZF1：治疗自身免疫性疾病的重要靶点

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-13 DOI: 10.1016/j.clim.2025.110544

Siyuan Bu, Cong Ye, Shaozhe Cai, Lingli Dong

IKZF1 is a member of the Ikaros transcription factor family. It is involved in the regulation of the development and function of a variety of immune cells. Mutations or aberrant expression of IKZF1 are closely associated with the development of various immune-related diseases, including hematologic malignancies, solid tumors, and autoimmune diseases. In recent years, more and more studies have revealed the important role of IKZF1 in regulating immune responses, maintaining immune tolerance, and inhibiting the overactivation of immune cells. What's more, IKZF1 has been discovered to have a significant connection to the pathogenesis of autoimmune diseases. This review will summarize the role of IKZF1 in autoimmune diseases and its potential clinical applications.

IKZF1是Ikaros转录因子家族的一员。它参与调节多种免疫细胞的发育和功能。IKZF1的突变或异常表达与各种免疫相关疾病的发展密切相关，包括血液恶性肿瘤、实体瘤和自身免疫性疾病。近年来，越来越多的研究揭示了IKZF1在调节免疫应答、维持免疫耐受、抑制免疫细胞过度活化等方面的重要作用。更重要的是，IKZF1已被发现与自身免疫性疾病的发病机制有重要的联系。本文就IKZF1在自身免疫性疾病中的作用及其潜在的临床应用进行综述。

引用次数: 0

A national survey of four decades of hereditary angioedema prophylaxis: Efficacy and safety of old and new drugs 一项关于40年遗传性血管性水肿预防的全国调查：新旧药物的有效性和安全性。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-11 DOI: 10.1016/j.clim.2025.110542

Hanga Réka Horváth , Beáta Visy , Kinga Viktória Kőhalmi , Zsuzsanna Balla , Noémi Andrási , Ibolya Czaller , Zsuzsanna Zotter , Henriette Farkas

Background

Hereditary angioedema (HAE) imposes a significant burden on patients due to the unpredictability of attacks. Long-term prophylaxis (LTP) aims to prevent these episodes and improve quality of life. Over the past five decades, LTP options have evolved from non-specific treatments (fresh frozen plasma, attenuated androgens, antifibrinolytics) to more targeted therapies (intravenous or subcutaneous C1 inhibitor (C1INH), lanadelumab, berotralstat).

Objective

To assess the use, efficacy, and safety of various LTP therapies among Hungarian HAE patients.

Methods

Data from the Hungarian HAE Registry (1979–2023) were analysed, including LTP usage, attack rates, side effects, and laboratory parameters.

Results

Danazol and tranexamic acid use increased over the first 30 years but has declined in the last decade. Conversely, the use of modern LTP therapies and the proportion of patients relying solely on on-demand medication have significantly increased over the past decade. Danazol and tranexamic acid reduced attack rates in 60 % of patients without significant changes in the laboratory parameters at the lowest effective doses. Furthermore, 100 % of patients on subcutaneous C1INH, lanadelumab, and berotralstat experienced fewer attacks and improved quality of life compared to pre-treatment periods, with no serious side effects or significant laboratory abnormalities.

Conclusion

Modern prophylaxis usage is increasing among Hungarian HAE-C1INH patients, following the global trends. Both modern and traditional LTP options proved safe and effective in our patient population when used with appropriate monitoring.

背景：遗传性血管性水肿（HAE）由于发作的不可预测性给患者带来了沉重的负担。长期预防（LTP）旨在预防这些发作并改善生活质量。在过去的50年里，LTP的选择已经从非特异性治疗（新鲜冷冻血浆、减毒雄激素、抗纤溶药物）发展到更有针对性的治疗（静脉或皮下C1抑制剂（C1INH）、lanadelumab、贝曲司他）。目的：评估各种LTP治疗在匈牙利HAE患者中的使用、疗效和安全性。方法：分析匈牙利HAE登记处（1979-2023）的数据，包括LTP的使用、发病率、副作用和实验室参数。结果：达那唑和氨甲环酸的使用在前30 年有所增加，但在最近十年有所下降。相反，在过去十年中，现代LTP疗法的使用和完全依赖按需用药的患者比例显著增加。在最低有效剂量下，达那唑和氨甲环酸降低了60% %患者的发病率，而实验室参数没有显著变化。此外，与治疗前相比，100 %的皮下注射C1INH、lanadelumab和贝曲司他的患者发作次数更少，生活质量得到改善，没有严重的副作用或显著的实验室异常。结论：匈牙利HAE-C1INH患者的现代预防使用正在增加，与全球趋势一致。在适当的监测下，现代和传统的LTP方案在我们的患者群体中被证明是安全有效的。

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引用次数: 0

Activated CD4+ T cells upregulate PD-L1 expression on B cells through CD40/CD40L signaling and direct contact in systemic lupus erythematosus 在系统性红斑狼疮中，活化的CD4+ T细胞通过CD40/CD40L信号传导和直接接触上调B细胞的PD-L1表达

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-09 DOI: 10.1016/j.clim.2025.110535

Siyuan Lai , Ning Li , Songyue Chen , Yanxin Wang , Dengxiao Hong , Wenyan Xu , Zhongxin Chen , Baiqing Li , Changhao Xie

Programmed cell death protein 1 (PD-1) expression on T cells has been implicated in the pathogenesis of autoimmune diseases; however, the functional role of programmed death-ligand 1 (PD-L1) expression on B cells remains insufficiently characterized, particularly in the context of CD4⁺ T cell–mediated regulation in systemic lupus erythematosus (SLE). Flow cytometric analysis revealed that PD-L1⁺ B cells exhibited upregulated surface expression of the co-stimulatory molecules CD80 and CD86, alongside a concomitant downregulation in the expression of the antigen-presenting molecule human leukocyte antigen DR (HLA-DR). Furthermore, an elevated frequency of class-switched PD-L1⁺ B cells was observed in the peripheral blood of patients with SLE. Using co-culture systems and transwell assays, we demonstrated that CD4⁺ T cells modulate PD-L1 expression on B cells via direct cell–cell interactions. Mechanistically, this regulation was shown to be dependent on bidirectional CD40/CD40L signaling. These findings advance our understanding of PD-L1-mediated immunoregulation in SLE pathogenesis and identify PD-L1⁺ B cells as potential targets for therapeutic intervention.

程序性细胞死亡蛋白1 （PD-1）在T细胞上的表达与自身免疫性疾病的发病机制有关；然而，程序性死亡配体1 （PD-L1）在B细胞上表达的功能作用仍然没有得到充分的表征，特别是在系统性红斑狼疮（SLE）中CD4+ T细胞介导的调节的背景下。流式细胞术分析显示，PD-L1+ B细胞表面共刺激分子CD80和CD86表达上调，同时抗原呈递分子人白细胞抗原DR （HLA-DR）表达下调。此外，在SLE患者的外周血中观察到PD-L1+ B细胞类别转换频率升高。通过共培养系统和transwell实验，我们证明CD4+ T细胞通过直接的细胞间相互作用调节B细胞上PD-L1的表达。在机制上，这种调节被证明依赖于双向CD40/CD40L信号传导。这些发现促进了我们对SLE发病机制中PD-L1介导的免疫调节的理解，并确定了PD-L1+ B细胞作为治疗干预的潜在靶点。

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引用次数: 0

ProBNP, cytokines, and the Nrf2/HO-1 signaling pathway: A cross-sectional study on cardiovascular risk in rheumatoid arthritis ProBNP、细胞因子和Nrf2/HO-1信号通路：类风湿关节炎心血管风险的横断面研究

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-09 DOI: 10.1016/j.clim.2025.110541

Christiane Aguiar Nobre , Carlos Ewerton Maia Rodrigues , Natacha Xavier Cavalcante , Thácilla Siqueira Eugênio Nascimento , João Gabriel Marques Brayner , Giovanna Azevedo Sousa , Nayara Alves de Sousa , Regislane Pinto Ribeiro , Vanessa Maria Eufrásio de Fiqueirêdo , Giulia Albuquerque Paiva , José Jackson do Nascimento Costa , Paula Goes , Hellíada Vasconcelos Chaves , Ticiana Mont'Alverne Parente Feijão , Mirna Marques Bezerra

We evaluated associations between clinical/laboratory findings and serum cytokines, Nrf2/HO-1 pathway expression and cardiovascular risk in both RA patients and controls. Sixty RA patients and 60 controls were included in the study. Serum cytokine and proBNP levels were assessed by ELISA, while serum Nrf2 and HO-1 mRNA levels were quantified by qRT-PCR. The RA group (91.7 % women) and the control group (90 % women) were aged 52 ± 12 and 52 ± 13 years, respectively. ProBNP levels were higher in the RA group than in controls (p = 0.009). Nrf2 mRNA levels were higher (p < 0.001) and HO-1 mRNA levels were lower (p = 0.030) in the RA group than in controls. CDAI scores were significantly associated with serum IL-6 levels (p = 0.033). This study found a significant dysregulation in Nrf2/HO-1 pathway activity in RA patients, although without association with cardiovascular risk, RA-related clinical and laboratory variables. Moderate/high disease activity was positively associated with IL-6 levels.

我们评估了RA患者和对照组的临床/实验室结果与血清细胞因子、Nrf2/HO-1通路表达和心血管风险之间的关系。60名RA患者和60名对照者被纳入研究。ELISA法检测血清细胞因子和proBNP水平，qRT-PCR法检测血清Nrf2和HO-1 mRNA水平。RA组（91.7%为女性）和对照组（90%为女性）的年龄分别为52±12岁和52±13岁。RA组ProBNP水平高于对照组（p = 0.009）。Nrf2 mRNA水平升高(p <；0.001)， RA组HO-1 mRNA水平低于对照组（p = 0.030）。CDAI评分与血清IL-6水平显著相关（p = 0.033）。本研究发现RA患者Nrf2/HO-1通路活性明显失调，尽管与心血管风险、RA相关的临床和实验室变量无关。中度/高度疾病活动度与IL-6水平呈正相关。

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引用次数: 0

Clinical characteristics, risk factors and predictors of Parvovirus B19 infection in patients with autoimmune rheumatic inflammatory diseases: A nested case–control study 自身免疫性风湿性炎症患者细小病毒B19感染的临床特征、危险因素及预测因素：一项巢式病例对照研究

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-06 DOI: 10.1016/j.clim.2025.110537

Xinyue Zhang , Peixuan Liang , Ziwei Hu , Ziyun Zhang , Shaozhe Cai , Lingli Dong

This nested case-control study explored the clinical features and risk factors of Parvovirus B19 (B19V) infection in autoimmune rheumatic inflammatory disease (AIIRD) patients. A total of 86 B19V-positive cases and 172 matched controls were analyzed. Chronic liver diseases, cardiovascular diseases, a higher number of total infections, and the use of Mycophenolate Mofetil (MMF) were associated with an increased risk of B19V infection, whereas Iguratimod (IGU) was identified as a protective factor. Anemia, pneumonia, fever, myalgia, and hepatitis were significantly more common in B19V-infected patients, who were also more likely to experience varying degrees of cytopenia, particularly pancytopenia. Secondary hemophagocytic syndrome potentially attributable to B19V infection was observed in the case. Laboratory results showed lower blood cell counts and electrolytes, and higher anti-histone antibody positivity. Serum calcium, complement C4, and IgM were identified as key predictors in logistic and Lasso regression models.

Trial registration

Chinese Clinical Trial Register; https://www.chictr.org.cn/; ChiCTR2400089902.

本巢式病例对照研究探讨自身免疫性风湿性炎症（AIIRD）患者细小病毒B19 （B19V）感染的临床特征及危险因素。共分析86例b19v阳性病例和172例匹配对照。慢性肝病、心血管疾病、总感染人数较高以及使用霉酚酸酯（MMF）与B19V感染风险增加相关，而Iguratimod （IGU）被确定为一种保护因素。贫血、肺炎、发热、肌痛和肝炎在感染b19v的患者中更为常见，他们也更容易出现不同程度的细胞减少，尤其是全细胞减少。本病例观察到可能由B19V感染引起的继发性噬血细胞综合征。实验室结果显示血细胞计数和电解质较低，抗组蛋白抗体阳性较高。在logistic和Lasso回归模型中，血清钙、补体C4和IgM被确定为关键预测因子。中国临床试验注册；https://www.chictr.org.cn/;ChiCTR2400089902。

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引用次数: 0

Oral microbiota in allergic diseases, and sublingual allergen immunotherapy 过敏性疾病的口腔微生物群，以及舌下过敏原免疫治疗。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-06 DOI: 10.1016/j.clim.2025.110538

Umut Gazi , Nerin Nadir Bahceciler

Allergic diseases with their epidemic prevalence on the rise have been one of the major global health problems of the 21st century. The association of increased prevalence with lifestyle changes including increased urbanization, and hygiene practices highlighted the importance of host-microbiome interactions for maintaining immune homeostasis. In support, numerous studies demonstrated altered gut microbiome composition in allergic patients, and suggested dysbiosis as a possible cause of allergic diseases. Nevertheless, despite being the second largest microbiota in the human body, oral microbiota has not yet received the attention it deserves in the literature. With this review article, we aim to highlight its significance by summarizing the data obtained from studies evaluating oral microbiome composition in patients with allergic respiratory diseases. Additionally, their importance will be further elaborated by discussing the findings presented by animal and human studies investigating the possible effect of oral probiotic uptake to the clinical efficacy of sublingual allergen immunotherapy.

过敏性疾病的流行率呈上升趋势，已成为21世纪全球主要的健康问题之一。发病率的增加与生活方式的改变（包括城市化程度的提高）和卫生习惯的关系突出了宿主-微生物组相互作用对维持免疫稳态的重要性。为了支持这一观点，大量研究表明，过敏患者肠道微生物组组成发生改变，并提示生态失调可能是过敏性疾病的原因。然而，尽管口腔微生物群是人体第二大微生物群，但在文献中尚未得到应有的重视。在这篇综述文章中，我们旨在通过总结从评估过敏性呼吸道疾病患者口腔微生物组组成的研究中获得的数据来强调其重要性。此外，它们的重要性将通过讨论动物和人类研究的结果进一步阐述，这些研究调查了口服益生菌对舌下过敏原免疫治疗临床疗效的可能影响。

引用次数: 0

Differential control of mycobacterial growth ex vivo by COVID-19 patients is associated with CD8+ CD28+ T cells COVID-19患者体外分枝杆菌生长的差异控制与CD8+ CD28+ T细胞有关。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-06 DOI: 10.1016/j.clim.2025.110539

Alba Llibre , Henna Siddiqui , Julie G. Burel , Jamie Pillaye , Charlotte Jones , Harriet Hill , Sian E. Faustini , Ella F Windle , Hanfa Karim , Emma Sherry , Christopher A. Green , Martin Dedicoat , Zania Stamataki , Adam F. Cunningham , Matthew K. O'Shea

Diseases caused by SARS-CoV-2 and Mycobacterium tuberculosis (M.tb) represent two public health emergencies. In severe presentations of disease, both pathogens may share a biological niche in the lower respiratory tract. There is significant potential for SARS-CoV-2 and M.tb infections to be co-present within individuals and modulate the respective outcomes of either infection. Here, we investigated how whole blood samples, as well as CD4+ and CD8+ T cells, from individuals hospitalised with acute COVID-19 disease respond to mycobacterial challenge. To do this, samples were assessed by ex vivo mycobacterial growth inhibition assays, immune cell phenotyping by mass cytometry, and whole blood cytokine responses to mycobacterial antigens assessed by flow cytometry. These studies identified a subgroup of COVID-19 patients whose blood had an enhanced capacity to inhibit mycobacterial growth. The ability to control mycobacterial growth was associated with the presence of a distinct non-M.tb-specific CD8+ CD28+ T cell population. This work improves our understanding of factors involved in mycobacterial control.

由SARS-CoV-2和结核分枝杆菌引起的疾病是两种突发公共卫生事件。在疾病的严重表现中，两种病原体可能在下呼吸道共享一个生物生态位。SARS-CoV-2和结核分枝杆菌感染很有可能在个体中同时存在，并调节任何一种感染的各自结果。在这里，我们研究了急性COVID-19疾病住院患者的全血样本以及CD4+和CD8+ T细胞如何对分枝杆菌攻击做出反应。为此，通过体外分枝杆菌生长抑制试验评估样品，通过大量细胞术评估免疫细胞表型，并通过流式细胞术评估全血细胞因子对分枝杆菌抗原的反应。这些研究确定了一个血液抑制分枝杆菌生长能力增强的COVID-19患者亚组。控制分枝杆菌生长的能力与明显的非m。结核病特异性CD8+ CD28+ T细胞群。这项工作提高了我们对分枝杆菌控制相关因素的理解。

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引用次数: 0

Frequency of the AC-2 pattern's new variant (AC-30) and detection of different immunological relationships AC-2型新变异（AC-30）的频率及不同免疫学关系的检测

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology

Pub Date : 2025-06-05 DOI: 10.1016/j.clim.2025.110536

Mehmet Akif Durmuş , Selda Kömeç

Aim

This study investigates the frequency and autoantibody profile of the newly defined AC-30 pattern, a variant of the AC-2 dense fine speckled pattern, in patients undergoing antinuclear antibodies (ANA) testing via IIF on HEp-2 cells.

Result

A total of 12,369 samples collected between July 2024 and March 2025 were retrospectively analyzed. Upon re-evaluation, 147 samples (8.78 %) were identified as AC-30. The most common patterns were speckled (29.25 %), dense fine speckled (25.25 %), homogeneous (10.99 %), and AC-30 (8.78 %). Extractable nuclear antigen (ENA) analysis showed that 68.7 % of AC-30 samples were negative, while 31.3 % were positive most frequently for anti-DFS70, anti-dsDNA, anti-PM/Scl, and anti-SSA/Ro60.

Conclusion

Accurate identification of the AC-30 pattern is essential to prevent misclassification as AC-1 or AC-2, which may lead to diagnostic errors. Further multicenter studies are needed to clarify the clinical relevance and diagnostic value of the AC-30 pattern.

目的研究在HEp-2细胞上进行抗核抗体（ANA）检测的患者中，新定义的AC-30型（AC-2致密细斑型的一种变体）的频率和自身抗体谱。结果对2024年7月至2025年3月采集的12369份样本进行回顾性分析。经重新鉴定，147份（8.78%）样品为AC-30。最常见的是斑点型（29.25%）、密集细斑型（25.25%）、均匀型（10.99%）和AC-30型（8.78%）。可提取核抗原（ENA）分析结果显示，68.7%的AC-30样品呈阴性，其中抗dfs70、抗dsdna、抗pm /Scl和抗ssa /Ro60阳性的比例最高，为31.3%。结论准确识别AC-30型是防止误诊为AC-1或AC-2的关键。需要进一步的多中心研究来阐明AC-30模式的临床相关性和诊断价值。

引用次数: 0