Dataset Information

Identification and characterization of antigen-specific CD4⁺ T cells targeting renally expressed antigens in human lupus nephritis with two independent methods.

ABSTRACT: In the search for anti-renal autoreactivity in human lupus nephritis, we stimulated blood-derived CD4⁺ T cells from patients with systemic lupus erythematosus with various kidney lysates. Although only minor responses were detectable, these experiments led to the development of a search algorithm that combined autoantibody association with human lupus nephritis and target gene expression in inflamed kidneys. Applying this algorithm, five potential T cell antigens were identified. Blood-derived CD4⁺ T cells were then stimulated with these antigens. The cells were magnetically enriched prior to measurement with flow cytometry to facilitate the detection of very rare autoantigen-specific cells. The detected responses were dominated by IFN-?-producing CD4⁺ T cells. Additionally, IL-10-producing CD4⁺ T cells were found. In a next step, T cell reactivity to each single antigen was independently evaluated with T cell libraries and [³H]-thymidine incorporation assays. Here, Vimentin and Annexin A2 were identified as the main T cell targets. Finally, Vimentin reactive T cells were also found in the urine of three patients with active disease. Overall, our experiments show that antigen-specific CD4⁺ T cells targeting renally expressed antigens arise in human lupus nephritis and correlate with disease activity and are mainly of the Th1 subset.

SUBMITTER: Tesch S

PROVIDER: S-EPMC7718878 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Identification and characterization of antigen-specific CD4<sup>+</sup> T cells targeting renally expressed antigens in human lupus nephritis with two independent methods.

Tesch Sebastian S Abdirama Dimas D Grießbach Anna-Sophie AS Brand Hannah Antonia HA Goerlich Nina N Humrich Jens Y JY Bacher Petra P Hiepe Falk F Riemekasten Gabriela G Enghard Philipp P

Scientific reports 20201204 1

In the search for anti-renal autoreactivity in human lupus nephritis, we stimulated blood-derived CD4<sup>+</sup> T cells from patients with systemic lupus erythematosus with various kidney lysates. Although only minor responses were detectable, these experiments led to the development of a search algorithm that combined autoantibody association with human lupus nephritis and target gene expression in inflamed kidneys. Applying this algorithm, five potential T cell antigens were identified. Bloo ...[more]

PMID: 33277543

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Project description:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

Dataset Information

Identification and characterization of antigen-specific CD4+ T cells targeting renally expressed antigens in human lupus nephritis with two independent methods.

Publications

Identification and characterization of antigen-specific CD4<sup>+</sup> T cells targeting renally expressed antigens in human lupus nephritis with two independent methods.

Similar Datasets

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Identification and characterization of antigen-specific CD4⁺ T cells targeting renally expressed antigens in human lupus nephritis with two independent methods.