Soha Alena, Azina Inga, Zolovs Maksims, Miskina Darja Arina, Murasko Viktorija, Rozentale Baiba, Hartmane Ilona, Rubins Andris
Doctoral Program, Riga Stradiņš University, LV-1007 Riga, Latvia.
Latvian Center for Infectious Diseases, Riga East University Hospital, LV-1038 Riga, Latvia.
Medicina (Kaunas). 2025 Jun 15;61(6):1091. doi: 10.3390/medicina61061091.
This study explores the immunogenetic associations of human leukocyte antigens (HLAs) and cytokine levels in people living with HIV/AIDS (PLWH) who exhibit HIV-related skin disorders. HIV-related skin disorders, including inflammatory eruptions, atopic and seborrheic dermatitis, psoriasis, and pruritic papular eruption, are common among PLWH. These conditions may be influenced by genetic and immunological factors. This study aims to investigate the associations between HLA class II alleles, cytokine levels, and the presence of HIV-related dermatoses, providing insights into genetic susceptibility and immune mechanisms. This study included 115 PLWH with HIV-related skin disorders and a control group of 80 healthy individuals. HLA allele frequencies were analyzed, and cytokine levels (IL-1β, IL-10, IFN-y) were measured in blood samples. Statistical analyses were performed to identify significant differences in allele frequencies and cytokine responses between the groups. Risk alleles (DQB10201:0301, OR = 19.4 and DQA10101:0501, OR = 4.2) and protective alleles (DRB107:13, OR = 0.19, DRB101:13, OR = 0.09, DRB104:11, OR = 0.07, and DQA10501:0501, OR = 0.24) showed statistically significant differences in frequency ( < 0.05) between PLWH and healthy controls. The protective DQA10501:0501 allele was associated with elevated levels of IL-1β ( < 0.001, r = 0.79) and IL-10 ( = 0.010, r = 0.63). Increased IL-1β levels may enhance immune responses, while higher IL-10 levels may exert anti-inflammatory effects, potentially reducing susceptibility to HIV-related dermatoses. Regression analysis revealed that IL-1β (Exp(B) = 0.76, < 0.001) and IFN-γ (Exp(B) = 1.06, = 0.043) are significant predictors for the likelihood of developing HIV-related dermatoses. An increase in IL-1β levels reduced this likelihood by 24%, while an increase in IFN-γ levels increased it by 6%. The findings emphasize the interaction between HLA class II alleles and cytokine profiles in determining genetic risk and clinical outcomes in PLWH with HIV-related skin disorders. Protective alleles, such as DQA10501:0501, may contribute to immune regulation, offering potential targets for therapeutic interventions in PLWH with dermatoses. Our results highlight the importance of IL-1β and IFN-γ as key modulators in the progression of HIV infection and the development of HIV-related dermatoses. Further research is needed to explore the mechanisms underlying these associations, particularly in the Latvian population, to inform targeted therapeutic strategies.
本研究探讨了感染人类免疫缺陷病毒/获得性免疫综合征（HIV/AIDS）且患有与HIV相关皮肤疾病的人群中人类白细胞抗原（HLA）与细胞因子水平的免疫遗传学关联。与HIV相关的皮肤疾病，包括炎症性皮疹、特应性皮炎和脂溢性皮炎、银屑病以及瘙痒性丘疹性皮疹，在HIV感染者中很常见。这些病症可能受遗传和免疫因素影响。本研究旨在调查HLA II类等位基因、细胞因子水平与HIV相关皮肤病之间的关联，以深入了解遗传易感性和免疫机制。本研究纳入了115名患有与HIV相关皮肤疾病的HIV感染者以及80名健康个体作为对照组。分析了HLA等位基因频率，并在血样中测量了细胞因子水平（IL-1β、IL-10、IFN-γ）。进行了统计分析，以确定两组之间等位基因频率和细胞因子反应的显著差异。风险等位基因（DQB10201:0301，OR = 19.4；DQA10101:0501，OR = 4.2）和保护性等位基因（DRB107:13，OR = 0.19；DRB101:13，OR = 0.09；DRB104:11，OR = 0.07；DQA10501:0501，OR = 0.24）在HIV感染者和健康对照之间的频率差异具有统计学意义（P < 0.05）。保护性DQA10501:0501等位基因与IL-1β水平升高（P < 0.001，r = 0.79）和IL-10水平升高（P = 0.010，r = 0.63）相关。IL-1β水平升高可能增强免疫反应，而较高的IL-1水平可能发挥抗炎作用，潜在地降低对HIV相关皮肤病的易感性。回归分析显示，IL-1β（Exp(B) = 0.76，P < 0.001）和IFN-γ（Exp(B) = 1.06，P = 0.043）是发生HIV相关皮肤病可能性的显著预测因子。IL-1β水平升高使这种可能性降低24%，而IFN-γ水平升高使其增加6%。研究结果强调了HLA II类等位基因与细胞因子谱在确定患有与HIV相关皮肤疾病的HIV感染者的遗传风险和临床结局中的相互作用。保护性等位基因，如DQA10501:0501，可能有助于免疫调节，为患有皮肤病的HIV感染者的治疗干预提供潜在靶点。我们的结果突出了IL-1β和IFN-γ作为HIV感染进展和HIV相关皮肤病发展的关键调节因子的重要性。需要进一步研究以探索这些关联背后的机制，特别是在拉脱维亚人群中，为制定有针对性的治疗策略提供依据。
