Deposition of antibodies to the collagen‐like region of C1Q in renal glomeruli of patients with proliferative lupus glomerulonephritis

Mannik, Mart; Wener, Mark H.

doi:10.1002/art.1780400819

Cited by 104 publications

(68 citation statements)

References 29 publications

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“…Fourteen-month-old mice with high titres of anti-C1q antibodies in serum had an enrichment of antiC1q in their kidneys. This finding is in line with the finding of anti-C1q antibodies in renal tissue of MRL/MpJ-lpr/lpr mice [9] as well as in post-mortem material of end-stage kidneys from patients with lupus nephritis [16]. At the age of 14 months some MRL/MpJ +/+ mice exhibited GN with increased glomerular cellularity as well as glomerular IgG, C1q and/or C3 deposition.…”

Section: Discussionsupporting

confidence: 89%

Anti-C1q autoantibodies do not correlate with the occurrence or severity of experimental lupus nephritis

Bigler

Hopfer

Danner

et al. 2010

Molecular Immunology

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Section: Discussionsupporting

confidence: 89%

Anti-C1q autoantibodies do not correlate with the occurrence or severity of experimental lupus nephritis

Bigler

Hopfer

Danner

et al. 2010

Molecular Immunology

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“…This approach has been used in most of the reports describing circulating anti-C1q autoantibody (as discussed in Seelen et al 7 and Sinico et al 8) and shown to yield results that are highly correlated with measurements of anti-C1q binding to the collagen-like region of C1q at physiologic NaCl concentration (9). The collagen-like region is considered to contain the major anti-C1q epitope in patients with active SLE (10)(11)(12), and it is the epitope for anti-C1q antibodies isolated from the glomeruli of patients with LN (13).…”

Section: Anticomplement Assaysmentioning

confidence: 99%

Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its Flare

Birmingham

Bitter

Ndukwe

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Autoantibodies to complement C1q (anti-C1q) are associated with the diagnosis of lupus nephritis. In this study, we compare anti-C1q IgG with another complement autoantibody, anti-C3b IgG, as a biomarker of lupus nephritis and lupus nephritis flare.Design, setting, participants, & measurements Our investigation involved the Ohio SLE Study, a prospective observational cohort of patients with recurrently active lupus who were followed bimonthly. Serum anti-C1q and anti-C3b IgG levels were assessed cross-sectionally by ELISA in 40 normal controls and 114 patients in the Ohio SLE Study (41 nonrenal and 73 lupus nephritis) at study entry, and longitudinally in a subset of patients in the Ohio SLE Study with anti-C1q-positive lupus nephritis in samples collected every 2 months for 8 months leading up to lupus nephritis flare (n=16 patients). ResultsIn the cross-sectional analysis, compared with anti-C1q IgG, anti-C3b IgG was less sensitive (36% versus 63%) but more specific (98% versus 71%) for lupus nephritis. Only anti-C3b IgG was associated with patients with lupus nephritis who experienced at least one lupus nephritis flare during the Ohio SLE Study period (P,0.01). In the longitudinal analysis, circulating levels of anti-C1q IgG increased at the time of lupus nephritis flare only in patients who were anti-C3b positive (P=0.02), with significant increases occurring from 6 (38% increase) and 4 months (41% increase) before flare. Anti-C3b IgG levels also trended up at lupus nephritis flare, although the change did not reach statistical significance (P=0.07). Neither autoantibody increased 2 months before flare.Conclusions Although not as prevalent as anti-C1q IgG, anti-C3b IgG showed nearly complete specificity for lupus nephritis. The presence of anti-C3b IgG identified patients with lupus nephritis who were prone to flare and in whom serial measurements of markers associated with complement, such as anti-C1q IgG, may be useful to monitor lupus nephritis activity.

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“…Anti-C1q autoantibodies have been suggested to be closely associated with LN (10). This association is concluded from the correlation between anti-C1q autoantibody positivity and renal involvement (11,12), the predictive value of anti-C1q autoantibody titers for flares of nephritis (13,14), and the accumulation of anti-C1q autoantibodies in LN kidneys (15,16). Conversely, in the absence of anti-C1q autoantibodies, no LN develops (17,18).…”

Section: Introductionmentioning

confidence: 99%

Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes

Trouw¹,

Groeneveld²,

Seelen³

et al. 2004

J. Clin. Invest.

200

134

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Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, in SLE the presence of anti-C1q is associated with the occurrence of nephritis. We have generated mouse anti-mouse C1q mAb's and used murine models to investigate whether anti-C1q autoantibodies actually contribute to renal pathology in glomerular immune complex disease. Administration of anti-C1q mAb JL-1, which recognizes the collagen-like region of C1q, resulted in glomerular deposition of C1q and anti-C1q autoantibodies and mild granulocyte influx, but no overt renal damage. However, combination of JL-1 with a subnephritogenic dose of C1q-fixing anti-glomerular basement membrane (anti-GBM) antibodies enhanced renal damage characterized by persistently increased levels of infiltrating granulocytes, major histological changes, and increased albuminuria. This was not observed when a non-C1q-fixing anti-GBM preparation was used. Experiments with different knockout mice showed that renal damage was dependent not only on glomerular C1q and complement activation but also on Fcγ receptors. In conclusion, anti-C1q autoantibodies deposit in glomeruli together with C1q but induce overt renal disease only in the context of glomerular immune complex disease. This provides an explanation why anti-C1q antibodies are especially pathogenic in patients with SLE.

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Deposition of antibodies to the collagen‐like region of C1Q in renal glomeruli of patients with proliferative lupus glomerulonephritis

Cited by 104 publications

References 29 publications

Anti-C1q autoantibodies do not correlate with the occurrence or severity of experimental lupus nephritis

Anti-C1q autoantibodies do not correlate with the occurrence or severity of experimental lupus nephritis

Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its Flare

Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes

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