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First published online September 29, 2011

Prospective assessment of C4d deposits on circulating cells and renal tissues in lupus nephritis: a pilot study

I Batal, K Liang, S Bastacky, LP Kiss, T McHale, NL Wilson, B Paul, A Lertratanakul, JM Ahearn, SM Manzi, and AH Kao [email protected]View all authors and affiliations

Volume 21, Issue 1

https://doi.org/10.1177/0961203311422093

Abstract

Complement activation plays a key role in the pathogenesis of lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE). We prospectively evaluated 15 LN subjects and two control groups: 13 non-SLE renal subjects (control A) and 239 SLE subjects without LN (control B). All had C4d levels on circulating erythrocytes (E-C4d), reticulocytes (R-C4d) and platelets (P-C4d) measured by flow cytometry, while C4d deposition in renal tissue was semiquantitatively assessed in LN subjects and control A using immunoperoxidase staining.

Compared with control A, LN biopsies had higher glomerular-C4d scores (p = 0.003), which were associated with more frequent granular glomerular immunofluorescence staining and electron dense deposits (p < 0.001). Compared with control A and B groups, LN subjects had higher E-C4d (p = 0.002 and p = 0.005) and R-C4d levels (p = 0.002 and p = 0.008), respectively. LN subjects were more likely to have P-C4d compared with control A (p = 0.016). In LN, only E-C4d correlated with National Institutes of Health (NIH) activity index (r = 0.55, p = 0.04).

In conclusion, LN biopsies showed frequent glomerular-C4d staining associated with immune complex deposits. LN subjects had higher E-C4d and R-C4d levels compared with both control groups. E-C4d levels also correlated with NIH activity index. These findings suggest a potential role of C4d on circulating cells as a biomarker for lupus nephritis.

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Volume 21, Issue 1

Pages: 13 - 26

Article first published online: September 29, 2011

Issue published: January 2012

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PubMed: 21959138

Authors

Affiliations

I Batal^*

Department of Pathology, University of Pittsburgh, USA

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K Liang^*

Division of Nephrology, University of Pittsburgh, USA

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S Bastacky

Department of Pathology, University of Pittsburgh, USA

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LP Kiss

Department of Pathology, University of Pittsburgh, USA

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T McHale

Department of Pathology, University of Pittsburgh, USA

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NL Wilson

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, USA

Lupus Center of Excellence, West Penn Allegheny Health System, USA

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B Paul

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, USA

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A Lertratanakul

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, USA

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JM Ahearn

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, USA

Lupus Center of Excellence, West Penn Allegheny Health System, USA

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SM Manzi

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, USA

University of Pittsburgh Graduate School of Public Health, USA

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AH Kao

Division of Rheumatology and Clinical Immunology, University of Pittsburgh, USA

Lupus Center of Excellence, West Penn Allegheny Health System, USA

[email protected]

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Notes

Amy H Kao MD MPH, Lupus Center of Excellence, West Penn Allegheny Health System, 4800 Friendship Avenue, North Tower Suite 2600, Pittsburgh, PA 15224, USA Email: [email protected]

*

Both authors contributed similarly to this work.

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