Frequency of anti-hsp60, -65 and -70 antibodies in sera of
patients with juvenile idiopathic arthritis
Denisa Zlackaa,*, Pavla Vavrincovab, Thi Thu Hien Nguyena, Ilona Hromadnikovaa
aCell Biology Laboratory, Department of Paediatrics, University Hospital Motol, 2nd Medical Faculty, Charles University,
V Uvalu 84, 15006 Prague 5, Czech Republic
bRheumatology Outpatient Department, University Hospital Motol, 2nd Medical Faculty, Charles University, Prague, Czech Republic
Received 20 April 2006; revised 14 June 2006; accepted 27 June 2006
Cross-reactivity between microbial and human heat shock proteins (hsps) led to the concept that hsp might be involved in the etiopathogen-
esis of autoimmune diseases. We investigated antibodies to recombinant human hsp60, recombinant Mycobacterium bovis hsp65 and to stress-
inducible recombinant human hsp70 using enzyme-linked immunosorbent assay (ELISA) in sera of 209 juvenile idiopathic arthritis (JIA)
patients and 50 healthy controls. Anti-hsp60 antibodies did not exceed the control level in any JIA patient. The numbers of JIA patients (16/209,
7.6%) who raised anti-hsp65 antibodies was equal to healthy controls (4/50, 8%). Elevated levels of antibodies against hsp70 were found in
a cohort of patients with JIA (36.8%) when compared with age-matched healthy individuals (2%). These antibodies were predominantly of
IgG isotype in systemic disease and IgM isotype in oligoarthritis. In polyarthritis both IgG and IgM antibodies frequently occurred. Significantly
higher anti-hsp70 antibody levels were found in RF-positive JIA patients. The levels of anti-hsp70 antibodies correlated with the severity of
disease evaluated on the basis of Steinbrocker’s functional classification and rtg staging system. No association between anti-hsp70 antibody
levels and ANA, HLA B27 and disease duration (less than 2 years ? more than 2 years) was observed except IgM anti-hsp70 antibody where
significantly higher levels were also detected in HLA B27-positive patients. The prevalence of anti-hsp70 antibodies is much higher in JIA
patients when compared with healthy controls, suggesting their possible role in pathological mechanism of the disease.
? 2006 Elsevier Ltd. All rights reserved.
Keywords: Antibodies; Autoimmune disease; Heat shock protein; Juvenile idiopathic arthritis
The heat shock proteins (hsps) are a group of highly con-
served proteins classified according to their molecular
weights, produced by cells of prokaryotic and eukaryotic ori-
gin under normal as well as stressful conditions [1e4]. The
heat shock proteins are present in low concentrations in nor-
mal unstressed cells [5,6], where they play important
physiological roles including that of chaperones to assist in
proper folding and assembly of polypeptides [7e15], intracel-
lular transport of other proteins between different intracellular
compartments and MHCepeptide complex processing [16e
20]. Current evidence suggests that stress proteins may be im-
portant elements in the infectious aetiology and pathogenesis
of various autoimmune diseases involving rheumatoid and
juvenile idiopathic arthritis [21e26].
These proteins are considered one of the superantigens and
are the immunodominant antigens of various microbial patho-
gens inducing strong humoral and cellular immune responses
in numerous infections caused by bacteria, protozoa, fungi and
nematodes [27e32]. Numerous reports have suggested that
a connection between an infection and the onset of autoim-
mune disease exists due to the cross-reactivity between some
Abbreviations: ELISA, enzyme-linked immunosorbent assay; Hsp, heat
shock protein; JIA, juvenile idiopathic arthritis.
* Corresponding author. Tel.: þ420 22 443 2023/2022; fax: þ420 22 443
E-mail addresses: email@example.com (D. Zlacka), pavla.vavrincova@
lfmotol.cuni.cz (P. Vavrincova), firstname.lastname@example.org (T.T. Hien Nguyen),
email@example.com (I. Hromadnikova).
0896-8411/$ - see front matter ? 2006 Elsevier Ltd. All rights reserved.
Journal of Autoimmunity 27 (2006) 81e88
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