Background/Purpose: In NZM2328 (NZM), a mouse model of proliferative lupus glomerulonephritis (GN), lupus GN can be categorized to four stages, i.e. normal, acute GN (aGN), early chronic or transitional GN (tGN) and chronic GN (cGN). There is a high incidence of lupus GN in homozygous C1q deficiency and a marked incidence of severe lupus GN in presence of anti-C1q Ab in man. Interrogation of the microarray data from dissected NZM glomeruli indicates the C1q transcripts are increased in all stages of GN. At aGN this increase may be accountable by infiltrating macrophages. The reason for the increase in C1q transcripts at both tGN and cGN is not clear.

Methods: Podocytes, mesangial and endothelial cells were sorted from anti-GBM treated NZM mice and normal controls by flow cytometry with Abs specific for these populations. Q-PCR (C1qa, C1qb and C1qc) was performed on sorted cells. Similarly Q-PCR for C1q was performed on tubular cells isolated by laser microdissection from C57BL/6, NZM and NZM.Lc1R27 (R27), a NZM congenic line resistant to the progression of aGN to cGN despite the presence of immune complexes and complement activation. In situ hybridization (ISH) was performed with C1qc riboprobe. Immunofluorescence (IF) was done on kidneys with cell-specific and anti-C1q Abs tagged with different flourochromes and analyzed by confocal microscopy. Similarly IF was done on human renal biopsies and on urinary cells from normal and lupus patients. IF staining was also done on podocyte lines derived from NZM transformed by a temperature sensitive virus containing the SV40 large T Ag.

Results: C1q mRNA was detected in podocytes isolated from the kidneys of NZM treated with anti-GBM Abs. ISH collaborated this finding. At the protein level, C1q expression was shown by confocal microscopy with Abs to C1q and synaptopodin, a podocyte-specific protein. Similarly the presence of C1q was shown in podocytes of NZM kidneys with tGN and cGN but not in NZM or R27 kidneys with aGN. The presence of C1q was shown in one of four NZM podocyte cell lines. With “normal” renal tissue from patients with renal cell carcinoma and lupus GN renal biopsies (Classes II-IV), C1q expression by podocytes was limited to biopsies with Class III or IV lupus GN. The presence of C1q positive podocytes in the urine of five lupus patients with severe proteinuria and telescopic cellular elements (presumably class IV) was demonstrated. Similarly increased expression of C1q by tubular cells in severe GN was documented.

Conclusion: C1q is shown for the first time to be made by podocytes. Its expression is detected in two models of immune complex mediated GN. Its expression is detected in podocytes from kidney biopsies and in patients’ urine. The expression of C3 in podocytes and in tubular cells in diseased kidneys was also found. The function of these expressed complement components in lupus GN remains to be determined in view of the recent documented role of C1q and C3 in CNS. Our findings suggest locally produced complements may have more profound effects on the kidney. The presence of C1q positive podocytes suggests that this can be useful as a biomarker for diagnostic purpose and for monitoring the effectiveness of therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-c1q-by-podocytes-at-late-stages-of-proliferative-lupus-glomerulonephritis/