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Kidney Int. 2019 Mar;95(3):655-665. doi: 10.1016/j.kint.2018.09.027. Epub 2019 Jan 14.

Glomerular membrane attack complex is not a reliable marker of ongoing C5 activation in lupus nephritis.

Author information

1
Centre for Inflammatory Disease, Imperial College London, London, UK.
2
Ra Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.
3
Division of Rheumatology, Department of Medicine, Karolinska Institutet and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
4
Centre for Inflammatory Disease, Imperial College London, London, UK. Electronic address: t.h.cook@imperial.ac.uk.

Abstract

Complement plays an important role in the pathogenesis of lupus nephritis (LN). With the emergence of therapeutic complement inhibition, there is a need to identify patients in whom complement-driven inflammation is a major cause of kidney injury in LN. Clinical and histopathological data were obtained retrospectively from 57 biopsies with class III, IV, and V LN. Biopsies were stained for complement components C9, C5b-9, C3c, and C3d and for the macrophage marker CD68. C9 and C5b-9 staining were highly correlated (r = 0.92 in the capillary wall). C5b-9 staining was detected in the mesangium and/or capillary wall of both active and chronic proliferative LN in all but one biopsy and in the capillary wall of class V LN in all biopsies. C5b-9 staining intensity in the tubular basement membrane correlated with markers of tubulointerstitial damage, and more intense capillary wall C5b-9 staining was significantly associated with nonresponse to conventional treatment. Glomerular C5b-9 staining intensity did not differ between active and chronic disease; in contrast, C3c and CD68 staining were associated with active disease. Evaluation of serial biopsies and comparison of staining in active and chronic LN demonstrated that C5b-9 staining persisted for months to years. These results suggest that C5b-9 staining is almost always present in LN, resolves slowly, and is not a reliable marker of ongoing glomerular C5 activation. This limits the utility of C5b-9 staining to identify patients who are most likely to benefit from C5 inhibition.

KEYWORDS:

complement; glomerulonephritis; renal pathology; systemic lupus erythematosus

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