IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritisReport as inadecuate




IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 15:R61

First Online: 25 May 2013Received: 30 October 2012Revised: 15 February 2013Accepted: 25 May 2013

Abstract

IntroductionSpondyloarthritis SpA, an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 HSP60, recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G IgG subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27.

MethodsIgG subclass antibodies IgG1, IgG2, IgG3 and IgG4 against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters.

ResultsElevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this antigen had low levels of IgG1, indicating an inverse association. Different IgG subclasses were produced against bacterial and human HSP60 in the same serum sample, IgG1 and IgG3, respectively, indicating that there was no cross-reaction.

ConclusionsA significant association was observed between axial SpA and the presence of IgG1-IgG3 antibodies to human HSP60 and of IgG1 to S. enterica Enteritidis and C. trachomatis. Generation of antibodies to human HSP60 was independent of the presence of antibodies to bacterial HSP60. No association was observed between clinical and MRI changes with antibodies over time. Altogether, such antibodies do not reflect the disease activity in these patients.

This study has been approved by the Regional Research Ethics Committee of Central Jutland, Denmark. Trial registration numbers: 20050046 and 20100083

KeywordsSpondyloarthritis heat shock protein 60 HSP60 HSPD1 HLA-B27 IgG subclass AbbreviationsASankylosing spondylitis

BASDAIBath Ankylosing Spondylitis Disease Activity Index

BASFIBath Ankylosing Spondylitis Functional Index

BASMIBath Ankylosing Spondylitis Metrology Index

CRPC-reactive protein

ELISAenzyme-linked immunosorbent assay

ESSGEuropean Spondyloarthropathy Study Group

ASASAssessment of SpondyloArthritis international Society

HChealthy control

HLA-B27human leukocyte antigen B27

HSPheat shock protein

Igimmunoglobulin

ILinterleukin

IQRinterquartile range

MRImagnetic resonance imaging

ODoptical density

PsApsoriatic arthritis

ReAreactive arthritis

SDstandard deviation

SIJsacroiliac joints

SpAspondyloarthritis

TFItubal factor infertility

USpAundifferentiated spondyloarthritis.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4234 contains supplementary material, which is available to authorized users.

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Author: Thomas Gelsing Carlsen - Astrid Hjelholt - Anne Grethe Jurik - Berit Schiøttz-Christensen - Anna Zejden - Gunna Christian

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



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