原发性免疫调节障碍的T细胞和自身抗体分析

T-cell and autoantibody profiling for primary immune regulatory disorders.

作者信息

Harris Emily M, Chamseddine Sarah, Chu Anne, Senkpeil Leetah, Nikiciuk Matthew, Bourdine Aleksandra, Magin Logan, Al-Musa Amer, Woods Brian, Ozdogan Elif, Saker Sarife, Hoytema van Konijnenburg David P, Yee Christina S K, Nelson Ryan W, Lee Pui, Halyabar Olha, Hale Rebecca C, Day-Lewis Megan, Henderson Lauren A, Nguyen Alan A, Elkins Megan, Ohsumi Toshiro K, Gutierrez-Arcelus Maria, Peyper Janique M, Platt Craig D, Grace Rachael F, LaBere Brenna, Chou Janet

机构信息

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Mass.

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.

出版信息

J Allergy Clin Immunol. 2025 Jun 18. doi: 10.1016/j.jaci.2025.06.007.

DOI:10.1016/j.jaci.2025.06.007

PMID:40541618

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12393799/

Abstract

BACKGROUND

Limited clinical tools exist for characterizing primary immune regulatory disorders (PIRD). Increased CD4CXCR5PD1 circulating T follicular helper (cTfh) cell percentages have been identified as a marker of active disease in some, but not all, autoimmune disorders.

OBJECTIVE

We sought to develop a diagnostic approach that combines measurements of cellular and serologic autoimmunity.

METHODS

We recruited 74 controls and 101 pediatric patients with PIRD with autoimmunity. Flow cytometry was used to measure CD4CXCR5 T cells expressing the chemokine receptors CXCR3 and/or CCR6. IgG and IgA autoantibodies were quantified in 56 patients and 20 controls using a microarray of 1616 full-length, conformationally intact protein antigens. The cTfh cell percentages exceeding 12% of CD4 T cells were considered increased, as previously published, and the 97.5th percentile in the controls was the upper limit of normal for CD4CXCR5 T cells expressing CXCR3 and/or CCR6 and autoantibody intensity and number.

RESULTS

We found that 27.7% of patients had increased percentages of CD4CXCR5PD1 cTfh cells, and 42.5% had increased percentages of CD4CXCR5 cells expressing CXCR3 and/or CCR6. Patients had significantly more diverse IgG and IgA autoantibodies than controls, and 37.5% of patients had increased numbers of high-titer autoantibodies. Integrating measurements of cTfh cells, CD4CXCR5 T cells with CXCR3 and/or CCR6, and numbers of high-titer autoantibodies had 71.4% sensitivity (95% CI 58.5%-81.6%) and 85.0% specificity (95% CI 64.0%-94.8%) for patients with PIRD compared with controls.

CONCLUSIONS

Integrating CD4 T-cell phenotyping and total burden of autoantibodies can enhance detection of autoimmunity in PIRD.

摘要

背景

用于表征原发性免疫调节障碍（PIRD）的临床工具有限。循环滤泡辅助性T细胞（cTfh）中CD4⁺CXCR5⁺PD-1⁺细胞百分比升高已被确定为某些（但并非所有）自身免疫性疾病活动期的标志物。

目的

我们试图开发一种结合细胞和血清自身免疫测量的诊断方法。

方法

我们招募了74名对照者和101名患有自身免疫性PIRD的儿科患者。采用流式细胞术检测表达趋化因子受体CXCR3和/或CCR6的CD4⁺CXCR5⁺ T细胞。使用包含1616种全长、构象完整的蛋白质抗原的微阵列，对56例患者和20名对照者的IgG和IgA自身抗体进行定量。如先前发表的研究一样，超过CD4⁺ T细胞12%的cTfh细胞百分比被视为升高，对照者中第97.5百分位数是表达CXCR3和/或CCR6的CD4⁺CXCR5⁺ T细胞以及自身抗体强度和数量的正常上限。

结果

我们发现27.7%的患者CD4⁺CXCR5⁺PD-1⁺ cTfh细胞百分比升高，42.5%的患者表达CXCR3和/或CCR6的CD4⁺CXCR5⁺细胞百分比升高。患者的IgG和IgA自身抗体种类明显多于对照者，37.5%的患者高滴度自身抗体数量增加。综合检测cTfh细胞、表达CXCR3和/或CCR6的CD4⁺CXCR5⁺ T细胞以及高滴度自身抗体数量，对于PIRD患者与对照者相比，敏感性为71.4%（95%CI 58.5%-81.6%），特异性为85.0%（95%CI 64.0%-94.8%）。