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Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch-Schonlein purpura nephritis.

ABSTRACT: Objectives: Immunoglobulin A vasculitis/Henoch-Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose-deficient IgA₁ was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear.

Methods: We compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA.

Results: GNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin- and/or granzyme B-positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up-regulated surface expressions of human leucocyte antigen DR (HLA-DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8⁺ cells and/or CD56⁺ cells and up-regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level.

Conclusion: Activated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN.

SUBMITTER: Imai T

PROVIDER: S-EPMC7684975 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch-Schönlein purpura nephritis.

Imai Takashi T Nishiyama Kei K Ueki Kenji K Tanaka Tamami T Kaku Yoshitsugu Y Hara Toshiro T Ohga Shouichi S

Clinical & translational immunology 20201124 11

<h4>Objectives</h4>Immunoglobulin A vasculitis/Henoch-Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose-deficient IgA<sub>1</sub> was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear.<h4>Methods</h4>We compared gene ...[more]

PMID: 33282293

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Project description:ObjectivesThe aims of the study were to identify whether left renal vein (LRV) entrapment was more prevalent in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) compared with other types of renal diseases, and the association of LRV entrapment with glomerular incidental IgA and galactose-deficient-IgA1 (Gd-IgA1) deposition.MethodsA total of 797 patients with biopsy-proven kidney diseases have been screened for LRV entrapment by color Doppler ultrasound, and the prevalence of LRV entrapment in different types of renal diseases were then analyzed. Propensity score matching analysis was used to adjust for age, gender, and body mass index. Immunostaining of Gd-IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens.ResultsLRV entrapment was diagnosed in 47 patients (6%) with several kinds of renal diseases in our cohort. A total of 32 (68%) LRV entrapments were combined with expanded IgAN (idiopathic IgAN and HSPN). The prevalence of LRV entrapment in expanded IgAN was significantly higher than that in non-expanded IgAN (17 vs. 2%, p < 0.001), even after adjustment for age, gender, and body mass index by propensity score matching analysis (13 vs. 2%, p < 0.001). Removing expanded IgAN and LN, glomerular incidental IgA deposition was observed to be significantly more common in patients with LRV entrapment compared with patients without it (43 vs. 9%, p < 0.001). Furthermore, in glomerular diseases with incidental IgA deposits, significantly much larger proportion of patients with LRV entrapment were positive for glomerular Gd-IgA1 in contrast to patients without LRV entrapment (5/5 vs. 5/17, p = 0.01).ConclusionsLRV entrapment coexisted with several kinds of renal diseases, with a significantly higher prevalence in patients with idiopathic IgAN and HSPN. In patients of LN and IgAN-unrelated disease with LRV entrapment, glomerular IgA and Gd-IgA1 deposition was more common compared with patients without LRV entrapment.

Project description:Background and objectiveHenoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP.MethodsPubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD).ResultsThirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61-1.19); age > 10 y (3.13, 1.39-7.07); male gender (1.36, 1.07-1.74); abdominal pain (1.94,1.24-3.04); gastrointestinal bleeding (1.86, 1.30-2.65); severe bowel angina (3.38, 1.17-9.80); persistent purpura (4.02, 1.22-13.25); relapse (4.70, 2.42-9.14); WBC > 15 × 109/L (2.42, 1.39-4.22); platelets > 500 × 109/L (2.98, 1.22-7.25); elevated antistreptolysin O (ASO) (2.17, 1.29-3.64); and decreased complement component 3 (C3) (3.13, 1.62-6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01-1.96).ConclusionThe following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early stages of HSP. However, the results should be interpreted cautiously due to the limitations of the studies.

Dataset Information

Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch-Schonlein purpura nephritis.

Publications

Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch-Schönlein purpura nephritis.

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