Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy?
The benefits of tonsillectomy in IgA nephropathy (IgAN) are still debated. Tonsillectomy may remove pathogen sources and reduce the mucosal associated lymphoid tissue (MALT), limiting degalactosylated IgA1 (deGal-IgA1) production, which is considered to be the initiating pathogenetic event leading to IgA glomerular deposition. In the European network VALIGA, 62/1147 IgAN patients underwent tonsillectomy (TxIgAN). In a cross-sectional study 15 of these patients were tested and compared to 45 non-tonsillectomized IgAN (no-TxIgAN) and healthy controls (HC) regarding levels of deGal-IgA1, and markers of innate immunity and oxidative stress, including toll-like receptors (TLR)2, 3, 4 and 9 mRNAs, proteasome (PS) and immunoproteasome (iPS) mRNAs in peripheral blood mononuclear cells (PBMC), and advanced oxidation protein products (AOPP). Levels of deGal-IgA1 were lower in TxIgAN than in no-TxIgAN (p = 0.015), but higher than in HC (p = 0.003). TLR mRNAs were more expressed in TxIgAN than in HC (TLR4, p = 0.021; TLR9, p = 0.027), and higher in TxIgAN than in no-TxIgAN (p ≤ 0.001 for TLR2, 4, 9). A switch from PS to iPS was detected in PBMC of TxIgAN in comparison to HC and it was higher than in no-TxIgAN [large multifunctional peptidase (LMP)2/β1, p = 0.039; LPM7/β5, p < 0.0001]. The levels of AOPP were significantly higher in TxIgAN than HC (p < 0.001) and no-TxIgAN (p = 0.033). In conclusion, the activation of innate immunity via TLRs and ubiquitin-proteasome pathways and the pro-oxidative milieu were not affected by tonsillectomy, even though the levels of aberrantly galactosylated IgA1 were lower in patients with IgAN who had tonsillectomy. The residual hyperactivation of innate immunity in tonsillectomized patients may result from extra-tonsillar MALT.
Division of Otorhinolaryngology, University Hospital Città della Salute e della Scienza di Torino, Turin, Italy.
Luca
L
Vergano
Elisa
E
Loiacono
Roberto
R
Albera
Rosanna
R
Coppo
Roberta
R
Camilla
Licia
L
Peruzzi
Alessandro
A
Amore
Maria Elena
ME
Donadio
Federica
F
Chiale
Alberto
A
Boido
Filippo
F
Mariano
Gianna
G
Mazzucco
Sara
S
Ravera
Giovanni
G
Cancarini
Riccardo
R
Magistroni
Giulietta
G
Beltrame
Cristiana
C
Rollino
Piero
P
Stratta
Marco
M
Quaglia
Roberto
R
Bergia
Raffaella
R
Cravero
Stefano
S
Cusinato
Luisa
L
Benozzi
Silvana
S
Savoldi
Carola
C
Licata
D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D062107:Advanced Oxidation Protein Products / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003546:Cysteine Endopeptidases / Q000235:genetics; D005260:Female; D005690:Galactose / Q000378:metabolism; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D064368:Healthy Volunteers; D006801:Humans; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics; D014068:Tonsillectomy; D055815:Young Adult
D062107:Advanced Oxidation Protein Products; D007070:Immunoglobulin A; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex; D005690:Galactose