Glomerular membrane attack complex is not a reliable marker of ongoing C5 activation in lupus nephritis
| Autor: | Wilson, H, Medjeral-Thomas, NR, Gilmore, AC, Trivedi, P, Seyb, K, Farzaneh-Far, R, Gunnarsson, I, Zickert, A, Cairns, TD, Lightstone, L, Cook, HT, Pickering, MC |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Adolescent Biopsy Kidney Glomerulus chemical and pharmacologic phenomena Complement Membrane Attack Complex Article Young Adult systemic lupus erythematosus renal pathology parasitic diseases Humans complement Complement Activation Aged Retrospective Studies Patient Selection Complement C5 Reproducibility of Results 1103 Clinical Sciences Middle Aged Urology & Nephrology Lupus Nephritis female genital diseases and pregnancy complications Female Biomarkers Immunosuppressive Agents glomerulonephritis |
| Zdroj: | Kidney International |
| Popis: | 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. Graphical abstract |
| Databáze: | OpenAIRE |
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