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Clinical Significance of C4d Deposition in Renal Tissues from Patients with Primary Sj&oumlgren's Syndrome--A Preliminary Study

By Wenli Xia, Bixia Gao, Lin Duan, Yan Li, Yubing Wen, Limeng Chen, Xuemei Li, Falei Zheng, Mingxi Li

Posted 27 Feb 2019
bioRxiv DOI: 10.1101/562215 (published DOI: 10.1186/s12882-019-1341-y)

Objectives: To evaluate renal expression of C4d, a complement component in the classical/mannose binding lectin (MBL) pathway, in patients with primary Sj&oumlgren's syndrome (pSS)-associated renal impairments. Methods: We retrospectively reviewed the clinical and pathological data from 39 patients with pSS presenting with renal impairments. C4d was examined in paraffin-embedded biopsy tissues using immunohistochemistry. Glomerular C4d positive was defined when >75% glomeruli were globally stained. Tubulointerstitial C4d (TI-C4d) were scored semi-quantitatively as 0 (absent), 1 (spotty or weak), 2 (patchy) and 3 (diffuse). A TI-C4d score ≥2 was considered TI-C4d positive and included in the TI-C4d+ group and vice versa. Peritubular capillary (PTC) C4d was scored as 0 (absent), 1 (0~10%, minimal), 2 (10%~50%, focal), and 3 (>50%, diffuse). Results: Glomerular C4d deposition was observed in all 8 patients with pSS-related membranous nephropathy (MN) without obvious C1q deposition. Two of 5 patients with mesangial proliferative glomerulonephritis and 1 of 2 patients with IgA nephropathy had mild mesangial C4d deposition. Sixteen patients (6 glomerular dominant and 10 tubulointerstitial dominant) presented TI-C4d score ≥2. Patients in the TI-C4d+ group exhibited a higher serum creatinine level at the time of renal biopsy (TI-C4d+ 132.5 [89.7, 165.5] vs. TI-C4d- 83.0 [70.7, 102.0] μmol/L, P=0.008). PTC C4d was observed in 12 patients, with each of minimal, focal and diffuse staining being noted in 4 patients. Conclusions: The MBL pathway of complement activation was potentially involved in pSS-related MN. Tubulointerstitial C4d might be a pathological marker of severe renal injury in patients with pSS-related renal impairments.

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