Intrarenal production of B-cell survival factors in human lupus nephritis.
The B-cell survival factors APRIL and BLyS are important for B-cell maturation and activation and contribute to human autoimmune diseases. Interference with B-cell function by targeting these molecules is currently being investigated in large clinical trials for systemic lupus erythematosus. The local expression patterns of APRIL and BLyS have not been investigated in detail in kidneys with lupus nephritis. We studied the mRNA expression of APRIL, BLyS, and the corresponding receptors BCMA, TACI, and BAFF-R in microdissected human biopsies with proliferative lupus nephritis (n=25) and compared it with pretransplant biopsies of living donors (n=9). APRIL and BLyS mRNA levels were significantly higher in glomeruli of patients with proliferative lupus nephritis (12- and 30-fold, respectively). Tubulointerstitial expression of APRIL, BLyS, BCMA, and TACI was also significantly elevated. To localize the respective proteins in the kidney, APRIL, BLyS, and BAFF-R were studied by immunohistochemistry in renal biopsies with proliferative (n=21) or membranous (n=8) lupus nephritis. APRIL was prominently expressed in glomeruli with proliferative, but not membranous, lupus nephritis. The staining pattern was consistent with mesangial cells. A prominent accumulation of CD68-positive cells was present in glomeruli in association with APRIL expression. APRIL, BLyS, and BAFF-R were also expressed in interstitial inflammatory cell accumulation. This is the first study, which details local expression of APRIL and BLyS in glomeruli and tubulointerstitium of human proliferative lupus nephritis. This information might help define intrarenal effects of APRIL and BLyS inhibition in human lupus nephritis.
Neusser
Matthias A
MA
Division of Nephrology, Department of Internal Medicine, University Hospital, Zurich, Switzerland.
Lindenmeyer
Maja T
MT
Edenhofer
Ilka
I
Gaiser
Stefanie
S
Kretzler
Matthias
M
Regele
Heinz
H
Segerer
Stephan
S
Cohen
Clemens D
CD
D000293:Adolescent; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics*; D001402:B-Lymphocytes; D002470:Cell Survival; D005260:Female; D015870:Gene Expression; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics* / Q000473:pathology; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics*; D055815:Young Adult
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D012333:RNA, Messenger; C435926:TNFRSF13C protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13