TY - JOUR
T1 - Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome
AU - Wang, Jing
AU - Wen, Yubing
AU - Zhou, Mengyu
AU - Shi, Xiaoxiao
AU - Jiang, Lanping
AU - Li, Mingxi
AU - Yu, Yang
AU - Li, Xuemei
AU - Li, Xuewang
AU - Zhang, Wen
AU - Lundquist, Andrew L.
AU - Chen, Limeng
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/6/2
Y1 - 2017/6/2
N2 - Background: This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Method: Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Results: Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21+ follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. Conclusion: We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.
AB - Background: This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Method: Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Results: Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21+ follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. Conclusion: We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.
KW - Cubilin
KW - Ectopic germinal center
KW - IL-17
KW - Megalin
KW - Primary Sjogren syndrome
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U2 - 10.1186/s13075-017-1317-x
DO - 10.1186/s13075-017-1317-x
M3 - Article
C2 - 28577559
AN - SCOPUS:85020029045
SN - 1478-6354
VL - 19
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 120
ER -