Autoantigenic nuclear proteins of a clinically atypical renal vasculitisReport as inadecuate




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Journal of Autoimmune Diseases

, 5:3

First Online: 14 July 2008Received: 04 December 2007Accepted: 14 July 2008

Abstract

BackgroundSystemic vasculitides constitute a heterogeneous group of diseases of autoimmunological origin characterized by inflammation of blood vessels and antibodies that react against autoantigens in a process that ultimately affects blood vessel walls. An important number of these patients present kidney disease. An endeavour of this area of research is the identification of autoantigens involved in these diseases. Accordingly, we used serum from a patient suffering from a microscopic polyangiitis, P-ANCA positive, manifesting a clinically atypical renal necrotizing glomerulonephritis and interstitial nephropathy for the identification of autoantigens; we also determined the prevalence of corresponding autoantibodies in other vasculitides, diabetic microangiopathy and in general population.

MethodsThe patient-s serum was used as a probe for the immunoscreening method SEREX to screen a human brain cDNA expression library.

ResultsFour positive clones were isolated and sequenced. Clones Jos002 code for protein HDAC5, Jos014 for TFC4, Jos107 for RTF1, and Jos313 for POLDIP3 polymerase. The four proteins are of nuclear localization. None of them had been reported as autoantigen. Recombinant proteins were synthesised and checked as antigens by western blot with different sera from controls and patients affected with other vasculitides and diabetic microangiopathy as well. Only the serum from the patient origin of this study recognized all recombinant proteins.

ConclusionWe identify four nuclear proteins, HDAC5, TFC4, RTF1 and POLDIP3 polymerase as new autoantigens that could be used as markers in the diagnosis of subfamilies in immune diseases, although we cannot determine the role of these proteins in the aetiopathogenic process.

List of abbreviationsANAAntinuclear antibody

ANCANeutrophile anticytoplasm antibody

c- or p- ANCACytoplasmic or perinuclear-ANCA

BLASTBasic local alignment search tool

bpBase pairs

cDNADNA complementary to RNA

CSSChurg-strauss syndrome

HDAC5Histone deacetylase 5

IPTGIsopropyl b-D-thiogalactopyranoside

kDaKilodaltons

PANPolyarteritis nodosa

MPAMicroscopic polyangiitis

MPOMyeloperoxidase

PBSPhosphate-buffered saline

PR3Proteinase 3

POLDIP3Polymerase -DNA-directed-delta interacting protein 3

RTF1Gene for TATA site selection by TATA box-binding protein

SEREXSerological identification of antigens by recombinant expression cloning

SLESystemic lupus erythematosus

TBSTris buffered saline

TFC4Transcription factor 4

WGSystemic Wegener-s granulomatosis.

Electronic supplementary materialThe online version of this article doi:10.1186-1740-2557-5-3 contains supplementary material, which is available to authorized users.

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Author: Julio Avila - Elisa Acosta - María-del-Valle Machargo - María-Francisca Arteaga - Eduardo Gallego - Haridian Cañete - Jos

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







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