HIV 阳性、CD4 计数低的人群中，结核分枝杆菌特异性 IFN-γ 和 IgG 反应之间存在差异。

Discrepancy between Mtb-specific IFN-γ and IgG responses in HIV-positive people with low CD4 counts.

机构信息

Africa Health Research Institute, Durban, South Africa; University of KwaZulu-Natal, Durban, South Africa.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.

出版信息

EBioMedicine. 2023 Apr;90:104504. doi: 10.1016/j.ebiom.2023.104504. Epub 2023 Mar 2.

DOI:10.1016/j.ebiom.2023.104504

PMID:36870197

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9996381/

Abstract

BACKGROUND

Tuberculosis (TB) is a leading infectious cause of death worldwide and treating latent TB infection (LTBI) with TB preventative therapy is a global priority. This study aimed to measure interferon gamma (IFN-γ) release assay (IGRA) positivity (the current reference standard for LTBI diagnosis) and Mtb-specific IgG antibodies in otherwise healthy adults without HIV and those living with HIV (PLWH).

METHODS

One-hundred and eighteen adults (65 without HIV and 53 antiretroviral-naïve PLWH), from a peri-urban setting in KwaZulu-Natal, South Africa were enrolled. IFN-γ released following stimulation with ESAT-6/CFP-10 peptides and plasma IgG antibodies specific for multiple Mtb antigens were measured using the QuantiFERON-TB Gold Plus (QFT) and customized Luminex assays, respectively. The relationships between QFT status, relative concentrations of anti-Mtb IgG, HIV-status, sex, age and CD4 count were analysed.

FINDINGS

Older age, male sex and higher CD4 count were independently associated with QFT positivity (p = 0.045, 0.05 and 0.002 respectively). There was no difference in QFT status between people with and without HIV infection (58% and 65% respectively, p = 0.06), but within CD4 count quartiles, people with HIV had higher QFT positivity than people without HIV (p = 0.008 (2nd quartile), <0.0001 (3rd quartile)). Concentrations of Mtb-specific IFN-γ were lowest, and relative concentrations of Mtb-specific IgGs were highest in PLWH in the lowest CD4 quartile.

INTERPRETATION

These results suggest that the QFT assay underestimates LTBI among immunosuppressed people with HIV and Mtb-specific IgG may be a useful alternative biomarker for Mtb infection. Further evaluation of how Mtb-specific antibodies can be leveraged to improve LTBI diagnosis is warranted, particularly in HIV-endemic areas.

FUNDINGS

NIH, AHRI, SHIP: SA-MRC and SANTHE.

摘要

背景

结核病（TB）是全球主要的传染病死因，用结核预防性治疗来治疗潜伏性结核感染（LTBI）是全球的重点。本研究旨在测量干扰素γ（IFN-γ）释放试验（IGRA）阳性（LTBI 诊断的当前参考标准）和无 HIV 的健康成年人以及艾滋病毒感染者（PLWH）中 Mtb 特异性 IgG 抗体。

方法

118 名成年人（65 名无 HIV 和 53 名未接受抗逆转录病毒治疗的 PLWH）来自南非夸祖鲁-纳塔尔省的一个城市周边地区。使用 QuantiFERON-TB Gold Plus（QFT）和定制的 Luminex 测定法分别测量 ESAT-6/CFP-10 肽刺激后释放的 IFN-γ和针对多种 Mtb 抗原的特异性血浆 IgG 抗体。分析 QFT 状态、抗 Mtb IgG 的相对浓度、HIV 状态、性别、年龄和 CD4 计数之间的关系。

结果

年龄较大、男性和较高的 CD4 计数与 QFT 阳性独立相关（p=0.045、0.05 和 0.002 分别）。感染 HIV 的人和未感染 HIV 的人之间的 QFT 状态没有差异（分别为 58%和 65%，p=0.06），但在 CD4 计数四分位中，感染 HIV 的人的 QFT 阳性率高于未感染 HIV 的人（p=0.008（第二四分位），<0.0001（第三四分位））。在 CD4 计数最低的四分位数中，PLWH 的 Mtb 特异性 IFN-γ浓度最低，而 Mtb 特异性 IgG 的相对浓度最高。