HIV感染患者中伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS）的皮肤浸润T细胞谱。
Skin infiltrating T-cell profile of drug reaction with eosinophilia and systemic symptoms (DRESS) reactions among HIV-infected patients.
作者信息
Chimbetete Tafadzwa, Choshi Phuti, Pedretti Sarah, Porter Mireille, Roberts Riyaadh, Lehloenya Rannakoe, Peter Jonathan
机构信息
Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town, South Africa.
出版信息
Front Med (Lausanne). 2023 May 5;10:1118527. doi: 10.3389/fmed.2023.1118527. eCollection 2023.
INTRODUCTION
Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) is more common in persons living with HIV (PLHIV), and first-line anti-TB drugs (FLTDs) and cotrimoxazole are the commonest offending drugs. Limited data is available on the skin infiltrating T-cell profile among DRESS patients with systemic CD4 T-cell depletion associated with HIV.
MATERIALS AND METHODS
HIV cases with validated DRESS phenotypes (possible, probable, or definite) and confirmed reactions to either one or multiple FLTDs and/or cotrimoxazole were chosen ( = 14). These cases were matched against controls of HIV-negative patients who developed DRESS ( = 5). Immunohistochemistry assays were carried out with the following antibodies: CD3, CD4, CD8, CD45RO and FoxP3. Positive cells were normalized to the number of CD3+ cells present.
RESULTS
Skin infiltrating T-cells were mainly found in the dermis. Dermal and epidermal CD4+ T-cells (and CD4+/CD8+ ratios) were lower in HIV-positive vs. negative DRESS; < 0.001 and = 0.004, respectively; without correlation to whole blood CD4 cell counts. In contrast, no difference in dermal CD4+FoxP3+ T-cells was found in HIV-positive vs. negative DRESS, median (IQR) CD4+FoxP3+ T-cells: [10 (0-30) cells/mm vs. 4 (3-8) cells/mm, = 0.325]. HIV-positive DRESS patients reacting to more than one drug had no difference in CD8+ T-cell infiltrates, but higher epidermal and dermal CD4+FoxP3+ T-cell infiltrates compared to single drug reactors.
CONCLUSION
DRESS, irrespective of HIV status, was associated with an increased skin infiltration of CD8+ T-cells, while CD4+ T-cells were lower in HIV-positive DRESS compared to HIV-negative DRESS skin. While inter-individual variation was high, the frequency of dermal CD4+FoxP3+ T-cells was higher in HIV-positive DRESS cases reacting to more than one drug. Further research is warranted to understand the clinical impact of these changes.
引言
药物超敏反应伴嗜酸性粒细胞增多和全身症状（DRESS）在人类免疫缺陷病毒（HIV）感染者（PLHIV）中更为常见，一线抗结核药物（FLTDs）和复方新诺明是最常见的致病药物。关于与HIV相关的全身CD4 T细胞耗竭的DRESS患者的皮肤浸润T细胞谱的数据有限。
材料与方法
选择具有确诊DRESS表型（可能、很可能或确诊）且对一种或多种FLTDs和/或复方新诺明有确诊反应的HIV病例（n = 14）。这些病例与发生DRESS的HIV阴性对照患者（n = 5）进行匹配。使用以下抗体进行免疫组织化学分析：CD3、CD4、CD8、CD45RO和FoxP3。将阳性细胞数量标准化为存在的CD3 +细胞数量。
结果
皮肤浸润T细胞主要见于真皮。HIV阳性DRESS患者的真皮和表皮CD4 + T细胞（以及CD4 + /CD8 +比率）低于HIV阴性DRESS患者；分别为P < 0.001和P = 0.004；与全血CD4细胞计数无关。相比之下，HIV阳性和阴性DRESS患者的真皮CD4 + FoxP3 + T细胞无差异，CD4 + FoxP3 + T细胞中位数（四分位间距）：[10（0 - 30）个细胞/mm²对4（3 - 8）个细胞/mm²，P = 0.325]。对多种药物有反应的HIV阳性DRESS患者的CD8 + T细胞浸润无差异，但与单一药物反应者相比，表皮和真皮CD4 + FoxP3 + T细胞浸润更高。
结论
无论HIV状态如何，DRESS都与CD8 + T细胞皮肤浸润增加有关，而HIV阳性DRESS患者的CD4 + T细胞低于HIV阴性DRESS患者的皮肤。虽然个体间差异很大，但对多种药物有反应的HIV阳性DRESS病例中真皮CD4 + FoxP3 + T细胞的频率更高。有必要进一步研究以了解这些变化的临床影响。
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