BACKGROUND: Henoch-Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown. METHODS: This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral blood mononuclear cells (PBMC). RESULTS: The expression of mRNAs encoding for TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases FoxP3mRNA and TGF-β1mRNA expression was significantly lower than in HC. A switch from PS to iPS (LMP2/β1) was detected only in PBMC of HSP and it correlated with the level of TLR2mRNA, which was selectively increased only in children with HSP. CONCLUSION: Children with HSP and pIgAN present with similar signs of engagement of the innate immunity and regulatory T cell depression. The increased immunoproteasome switch, which correlated with TLR2 activation, may suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This research area also deserves further investigation for possible therapeutic applications.
BACKGROUND: Henoch-Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown. METHODS: This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral blood mononuclear cells (PBMC). RESULTS: The expression of mRNAs encoding for TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases FoxP3mRNA and TGF-β1mRNA expression was significantly lower than in HC. A switch from PS to iPS (LMP2/β1) was detected only in PBMC of HSP and it correlated with the level of TLR2mRNA, which was selectively increased only in children with HSP. CONCLUSION:Children with HSP and pIgAN present with similar signs of engagement of the innate immunity and regulatory T cell depression. The increased immunoproteasome switch, which correlated with TLR2 activation, may suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This research area also deserves further investigation for possible therapeutic applications.
Authors: V Calvo-Río; J Loricera; L Martín; F Ortiz-Sanjuán; L Alvarez; M C González-Vela; D González-Lamuño; C Mata; P Gortázar; J Rueda-Gotor; M Arias; E Peiró; V M Martínez-Taboada; M A González-Gay; R Blanco Journal: Clin Exp Rheumatol Date: 2013-04-09 Impact factor: 4.473
Authors: Kari Ann Shirey; Wendy Lai; Alison J Scott; Michael Lipsky; Pragnesh Mistry; Lioubov M Pletneva; Christopher L Karp; Jaclyn McAlees; Theresa L Gioannini; Jerrold Weiss; Wilbur H Chen; Robert K Ernst; Daniel P Rossignol; Fabian Gusovsky; Jorge C G Blanco; Stefanie N Vogel Journal: Nature Date: 2013-05-01 Impact factor: 49.962
Authors: Jan Mersmann; Franziska Iskandar; Kathrina Latsch; Katharina Habeck; Vera Sprunck; René Zimmermann; Ralf R Schumann; Kai Zacharowski; Alexander Koch Journal: Mediators Inflamm Date: 2013-11-24 Impact factor: 4.711
Authors: Sari H Rytkönen; Petri Kulmala; Helena Autio-Harmainen; Pekka Arikoski; Kira Endén; Janne Kataja; Tuomo Karttunen; Matti Nuutinen; Timo Jahnukainen Journal: Pediatr Nephrol Date: 2017-09-11 Impact factor: 3.714