Increased Circulating T Lymphocytes Expressing HLA-DR in Kidney Transplant Recipients with Microcirculation Inflammation

Jung, Hee-Yeon; Kim, Yong Jin; Choi, Ji Young; Cho, Jang Hee; Kim, Yong Lim; Kim, Hyung Kee; Huh, Seung; Won, Dong Il; Kim, Chan Duck

doi:10.3346/jkms.2017.32.6.908

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…It was shown that HLA-DR expression on CD3 + T cells was higher in lupus patients with anti-DNA antibodies as compared to HC (47) and was higher on CD8 + T cells in patients experiencing a lupus flare (22). Similar observations were made in patients with rheumatoid arthritis (21, 53), antiphospholipid syndrome (54) and with rejection in solid organ transplantation (55).…”

Section: Discussionsupporting

confidence: 67%

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

et al. 2019

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Background: Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS.Methods: Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively.Results: Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for <5 years, 18 for 5–10 years and 27 for more than 10 years. The frequency of Tregs (CD4+CD25+CD127−FoxP3+) was significantly lower in CS exposed workers as compared to HC. We found an increased expression of the activation marker HLA-DR on T cells (CD3+, CD4+, and CD8+) of CS exposed workers as compared to HC. Tregs to activated T cells ratio was also lower in exposed subjects. In the latter, HLA-DR expression level and Tregs frequency were significantly associated with CS exposure duration. Serum autoantibody detection was significantly higher in CS exposed workers as compared to HC. Especially, among workers exposed more than 10 years, antinuclear antibodies and ANCA were detected in 44 and 22% among them, as compared to 5 and 2.5% in HC, respectively.Conclusion: This work shows that CS exposure is associated with a decrease of Tregs frequency, an increase of T cell activation status, and a tolerance breakdown against auto-antigens. These results show that alterations of the T cell compartment can be detected early over the course of CS exposure, preceding silicosis development or AID onset.

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Section: Discussionsupporting

confidence: 67%

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

et al. 2019

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“…Among the histopathological findings, the MI sum score of the renal allograft was reported to be significantly associated with immune activation in peripheral blood. 27 Similarly, previous studies have demonstrated that the detection of de novo DSA was significantly associated with microvascular lesions or peritubular capillaritis scores, 28 but not with scarring lesions. 10 11 Contrary to previous evidences, in our experience, we could not find any pathologic correlation with de novo DSA.…”

Section: Discussionmentioning

confidence: 74%

Characteristics and Clinical Significance of De Novo Donor-Specific Anti-HLA Antibodies after Kidney Transplantation

et al. 2018

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BackgroundThe association of de novo donor-specific anti-human leukocyte antigens (HLA) antibodies (DSA) and development of antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs) is still undetermined.MethodsWe prospectively screened de novo DSA in 167 KTRs during 32 months after kidney transplantation (KT). Timing of DSA detection was at 3, 6, and 12 months post-transplant and annually thereafter and when clinically indicated. DSA levels were determined by Luminex assays and expressed as mean fluorescence intensity (MFI). We evaluated the incidence, characteristics of DSA, and association between DSA and tacrolimus trough levels or AMR.ResultsDe novo DSA developed in 16 KTRs (9.6%) and acute AMR occurred more commonly in KTRs with de novo DSA compared to KTRs without de novo DSA (18.8% vs. 0%, P < 0.001). All de novo DSA were against class II antigens. The mean number of DSA was 1.8 ± 1.2 and the average MFI of DSA was 7,399 ± 5,470. Tacrolimus trough level during the first 0–2 months after KT was an independent predictor of DSA development (hazard ratio, 0.70; 95% confidence interval, 0.50–0.99; P = 0.043). No differences were found in the number of DSA, average MFI of DSA, and tacrolimus levels during the first year between de novo DSA-positive KTRs with AMR and those without AMR.ConclusionThe results of our study suggest that monitoring of DSA and maintaining proper tacrolimus levels are essential to prevent AMR during the initial period after KT.

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“…To determine the contribution of circulating dnDSAs to graft injury, the correlation between DSAs in peripheral blood and histopathologic lesions in renal allografts was evaluated. MFI sum score of renal allografts was shown to be associated with immune activation in peripheral blood [25], and the presence of dnDSAs has been linked to microvascular lesions or peritubular capillaritis [26] but not to scarring lesions [27][28]. Contrary to previous evidence, we did not nd any pathologic correlations with dnDSAs; there was no signi cant association between MFI sum score and the number and MFI of DSAs, which could be explained by the fewer episodes of acute rejection in our study population.…”

Section: Discussionmentioning

confidence: 99%

De Novo Donor-specific HLA Antibodies Reduce Graft Survival and Increase Risk of Kidney Transplant Rejection: A Single-Center Retrospective Study

Liu

Zhao

Kang

et al. 2020

Preprint

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Background: This study investigated the impact of posttransplantation de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection.Methods: This retrospective cohort study included 121 patients who received kidney transplants from deceased donors with negative complement-dependent cytotoxicity crossmatch. Based on the presence of dnDSAs, recipients were divided into dnDSA+ (n=31) and dnDSA− (n=90) groups. We evaluated the occurrence of rejection and long-term graft survival in the recipients along with pathologic changes in transplanted kidneys.Results: DnDSAs were identified in 31/121 (25.6%) patients, who had lower graft survival rates than patients without dnDSAs (P=0.007). There was no difference in graft survival rate between patients with high (≥4000) and low (<4000) DSA mean fluorescence intensity (P=0.669). The presence of dnDSA in serum was associated with a higher incidence of antigen- and T-cell–mediated rejection (P<0.0001). DnDSA+ and dnDSA− groups differed in terms of Banff score for arterial fibrointimal and arteriolar hyaline thickening (P<0.05).Conclusion: DnDSAs are associated with decreased long-term graft survival and increased rate of rejection, which is often accompanied by microcirculatory inflammation and positive C4d staining.

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Increased Circulating T Lymphocytes Expressing HLA-DR in Kidney Transplant Recipients with Microcirculation Inflammation

Cited by 9 publications

References 38 publications

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

Characteristics and Clinical Significance of De Novo Donor-Specific Anti-HLA Antibodies after Kidney Transplantation

De Novo Donor-specific HLA Antibodies Reduce Graft Survival and Increase Risk of Kidney Transplant Rejection: A Single-Center Retrospective Study

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