Plasma complement factor H is associated with disease activity of patients with ANCA-associated vasculitisReport as inadecuate




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Arthritis Research and Therapy

, 17:129

First Online: 21 May 2015Received: 05 January 2015Accepted: 14 May 2015

Abstract

IntroductionIncreasing evidences have demonstrated that activation of alternative complement pathway plays an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitis AAV. The current study aimed to investigate the association of complement factor H CFH, a key regulator of the alternative complement pathway, with the disease activity of AAV.

MethodsPlasma CFH levels were measured in 82 patients with myeloperoxidase MPO-AAV in active stage. Of the 82 patients, plasma CFH levels of 27 patients were longitudinally measured. Serum anti-CFH autoantibodies were screened in AAV patients. Circulating complement activation profiles including C4d, Bb, C3a, C5a and soluble C5b-9 of AAV patients in active stage were further detected. Associations between plasma CFH levels and clinicopathological parameters as well as the prognosis were analyzed.

ResultsPlasma CFH levels were significantly lower in active AAV patients compared with AAV patients in remission and normal controls. Correlation analysis showed that plasma CFH levels inversely correlated with initial serum creatinine, Birmingham Vasculitis Activity Score BVAS, proportion of total crescents and cellular crescents in renal specimens, and circulating levels of C3a, C5a and Sc5b-9, meanwhile positively correlated with estimated glomerular filtration rate eGFR, hemoglobin levels and circulating levels of C3. Moreover, multivariate survival analysis revealed that plasma CFH levels were independently associated with composite outcome of death or end stage renal disease ESRD in AAV patients, after adjusting for age, gender, hemoglobin level and urinary protein P = 0.03, HR 0.85, 95 % CI 0.73–0.98 or adjusting for age, gender, total crescents % and urinary protein P = 0.03, HR 0.85, 95 % CI 0.73–0.98, while not as an independent predictor after adjusting for age, gender, serum creatinine and urinary protein P = 0.57, HR 0.96, 95 % CI 0.83–1.11.

ConclusionIn conclusion, plasma CFH levels are associated with disease activity, and, to some extent, associated with composite outcomes of patients with MPO-ANCA-associated vasculitis.

AbbreviationsAAVAnti-neutrophil cytoplasmic antibody-associated vasculitis

aHUSAtypical hemolytic uremic syndrome

ANCAAnti-neutrophil cytoplasmic antibody

ANOVAAnalysis of variance

AUCArea under the curve

BSABovine serum albumin

BVASBirmingham Vasculitis Activity Score

CFHComplement factor H

CIConfidence interval

CRPC-reactive protein

eGFREstimated glomerular filtration rate

EGPAEosinophilic granulomatosis with polyangiits

ELISAEnzyme-linked immunosorbent assay

ESRDEnd stage renal disease

GPAGranulomatosis with polyangiitis

Hbhemoglobin

HRHazard ratio

mCRPModified-monomeric C-reactive protein

MPAMicroscopic polyangiitis

MPOMyeloperoxidase

P-ANCAPerinuclear anti-neutrophil cytoplasmic antibody

PBSPhosphate-buffered saline

PR3Proteinase 3

RLVRenal-limited vasculitis

ROCReceiver operating characteristic

SCRShort consensus repeats

SLESystemic lupus erythematosus

An erratum to this article is available at http:-dx.doi.org-10.1186-s13075-017-1298-9.

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Author: Su-Fang Chen - Feng-Mei Wang - Zhi-Ying Li - Feng Yu - Ming-Hui Zhao - Min Chen

Source: https://link.springer.com/







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