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Biomedical subjects

B J Prakken

Publications and source records attributed to B J Prakken.

13 recordsLinked to original sources
PubMed2003

The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat-shock protein 60 capable of producing the regulatory cytokine interleukin-10.

OBJECTIVE: To test the hypothesis that T cell reactivity to self heat-shock protein 60 (Hsp60) in patients with remitting juvenile idiopathic arthritis (JIA) is part of an antiinflammatory, regulatory mechanism. METHODS: Using peripheral blood-derived mononuclear cells (PBMCs) and synovial fluid-derived mononuclear cells (SFMCs) obtained from patients with JIA, we analyzed the expression of CD30 and the induction of regulatory cytokines in response to human and mycobacterial Hsp60. RESULTS: In oligoarticular JIA patients, in vitro activation of PBMCs and SFMCs with Hsp60 induced a high expression of CD30 on CD4+, activated (HLA-DR-positive), memory (CD45RO+) T cells. The expression of CD30 induced by human Hsp60 was much higher than that induced by mycobacterial Hsp60. In oligoarticular JIA patients with active disease, the expression of CD30 in response to human Hsp60 was paralleled by a high interleukin-10 (IL-10):interferon-gamma (IFNgamma) ratio. In addition, restimulated human Hsp60-specific T cell lines from oligoarticular JIA patients showed a high production of IL-10 and a low production of IFNgamma. In contrast, PBMCs and SFMCs from polyarticular JIA patients responded to human Hsp60 with virtually no expression of CD30 and a low IL-10:IFNgamma ratio. CONCLUSION: The results show that T cells responding to human Hsp60 in oligoarticular JIA patients express CD30, and during active phases of the disease, these T cells have a cytokine profile with a high IL-10:IFNgamma ratio. These findings suggest that in oligoarticular JIA patients, human Hsp60-specific CD4+ cells have a regulatory function and contribute to disease remission.

Arthritis, Juvenile↗
PubMed2001

Induction of IL-10 and inhibition of experimental arthritis are specific features of microbial heat shock proteins that are absent for other evolutionarily conserved immunodominant proteins.

Bacterial heat shock proteins (hsp) are evolutionary conserved immunodominant proteins that manifest amino acid homologies with hsp present in mammalian cells. Preimmunization with mycobacterial hsp65 has been found to protect against various forms of experimental arthritis. As these protective effects have previously been attributed to induction of self homologue cross-reactive T cell responses, the question was raised as to whether this protective effect could be extended to other highly conserved and immunodominant microbial Ags with mammalian homologues. Therefore, we immunized Lewis rats with conserved bacterial Ags (superoxide dismutase, aldolase, GAPDH, and hsp70). Although all Ags appeared highly immunogenic, we only found a protective effect in experimental arthritis after immunization with bacterial hsp70. The protective effect of hsp70 was accompanied with a switch in the subclasses of hsp70-specific Abs, suggesting the induction of Th2-like response. The most striking difference between immunization with hsp70 and all other immunodominant Ags was the expression of IL-10 found after immunization with hsp70. Even more, while immunization with hsp70 led to Ag-induced production of IL-10 and IL-4, immunization with aldolase led to increased production of IFN-gamma and TNF-alpha. Thus, the protective effect of conserved immunodominant proteins in experimental arthritis seems to be a specific feature of hsp. Therefore, hsp may offer unique possibilities for immunological intervention in inflammatory diseases.

Adoptive Transfer↗
PubMed1999

Lung function abnormalities and respiratory muscle weakness in children with juvenile chronic arthritis.

In contrast to adult rheumatoid arthritis (RA) little is known about the prevalence, nature and cause of lung function abnormalities in children with juvenile chronic arthritis (JCA). The aim of this study was to determine whether children with polyarticular and systemic onset JCA have lung function abnormalities and if so, whether they are related to pulmonary disease, thoracic and/or muscular involvement. We determined lung function and disability in 31 children with polyarticular and systemic JCA. Respiratory muscle function, thorax expansion and spine mobility were determined in the same patients, as well as in 32 matched healthy children. Peak expiratory flow (PEF) and forced vital capacity (FVC) were significantly reduced in JCA patients, when compared to reference values. Thorax expansion and spine mobility were normal, compared to paired controls. Maximum inspiratory (PI,max) and expiratory (PE,max) pressures were significantly reduced in patients compared to paired control subjects. A positive correlation was found between PE,max and FVC and PEF, an inverse correlation between expiratory pressure and disability. In conclusion, children with polyarticular and systemic juvenile chronic arthritis show a pronounced impairment in respiratory muscle strength, severe enough to cause mild lung function abnormalities and an increase in disability-scores.

Adolescent↗
PubMed1997

Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis.

Adjuvant arthritis (AA) can be induced in Lewis rats by immunization with mycobacterial antigens. Passive transfer of a T cell clone recognizing the 180-188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) was found to induce AA. In the present study, we investigated whether tolerance was obtained for this AA-associated T cell epitope after intranasal or s.c. administration of a peptide containing this epitope. Two 15-mer peptides containing the mycobacterial hsp60 sequences 176-190 and 211-225 were used; 176-190 contained the T cell epitope 180-188, which was recognized by the arthritogenic T cell clone A2b and was the immunodominant hsp60 T cell epitope after induction of AA, and 211-225 contained a T cell epitope that was recognized both after induction of arthritis with whole Mycobacterium tuberculosis and after immunization with mycobacterial hsp60. In rats treated intranasally or subcutaneously with 176-190 and immunized with mycobacterial hsp60, proliferative responses to 176-190 were reduced. Proliferative responses to 211-225 and to whole mycobacterial hsp60 were not affected. AA was inhibited intranasally in the 176-190-treated rats but not in the 211-225-treated rats. Moreover, intranasal 176-190 led to similar arthritis-protective effects in a nonmicrobially induced experimental arthritis (avridine-induced arthritis). Therefore, tolerance for a disease-triggering, microbial cartilage-mimicking epitope may cause resistance to arthritis irrespective of the actual trigger leading to development of the disease.

Administration, Intranasal↗
PubMed1996

(Altered) self peptides and the regulation of self reactivity in the peripheral T cell pool.

Tolerance for self has appeared incomplete for many self antigens. We have obtained experimental evidence that both for self heat shock proteins and T cell receptor V-gene products, reactive T cells are part of the normal immune repertoire. Furthermore, it has become apparent that stimulation of T cell responsiveness to these antigens, by using peptide immunisation or by transfer of activated T cells, raises resistance to experimentally induced autoimmune arthritis. In addition, available evidence has suggested that these reactivities may be functional during natural processes of disease remission. The observations with regard to heat-shock proteins have indicated that mechanism leading to disease resistance are most efficiently triggered by exposing the immune system to non-self antigens such as bacterial hsp's, which are similar to, but not identical to, self. Experimental evidence has been obtained, that conserved bacterial hsp peptides, may trigger self hsp reactive T cells, with disease suppressive regulatory potential. It is possible that such self hsp reactive T cells, being expanded by recognising bacterial peptides as full agonists, do, in fact, perceive the self epitopes as partial agonists, and therefore have the possibility of displaying downregulatory activity at the site of inflammation. Experiments with peptide analogs of self epitopes, being variants of disease critical T cell epitopes, have indeed suggested that also their activity in modulating disease may comply with the principles of dominant immunological tolerance.

Amino Acid Sequence↗
PubMed1995

Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis.

Synovial fluid and peripheral blood mononuclear cell proliferative responses to the 60-kD human heat shock protein (HSP60) were studied in 23 patients with juvenile chronic arthritis (JCA) and 7 non-JCA control patients. All patients showed active arthritis at the time of study. The patients were divided into two groups according to the presence (group A) or absence (group B) of T lymphocyte reactivity to human HSP60. We show that reactivity to human HSP60 is primarily, though not exclusively, occurring in patients with a remitting course of disease, i.e., the subgroup of HLA-B27 negative JCA patients with an oligoarticular onset. Immunohistochemical analysis of HSP expression in synovial membranes showed a significantly higher intensity of staining in JCA patients than in non-JCA controls. The results suggest that, in accordance with the earlier observation made in experimental models, T lymphocyte reactivity to human HSP60 in this subgroup of JCA patients may be part of T cell regulatory mechanisms that control the development of arthritis.

Adolescent↗
PubMedDate not supplied

The Dutch version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Dutch language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Dutch CHAQ was fully validated with 3 forward and 3 backward translations while the CHQ was already published and therefore it was revalidated. A total of 180 subjects were enrolled: 100 patients with JIA (17% systemic onset, 31% polyarticular onset, 18% extended oligoarticular subtype, and 34% persistent oligoarticular subtype) and 80 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Dutch version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Adolescent↗
PubMedDate not supplied

Heat-shock proteins and juvenile chronic arthritis.

Heat-shock proteins are a category of proteins that are synthesized under stressful conditions (such as increased temperatures) both by prokaryotic and eukaryotic cells. Heat-shock proteins are a major target of the immune response and thus can be considered dominant antigens. Under physiological circumstances the response to heat-shock proteins is considered to play a role in the overall defence against bacterial infections. An aberrant immune response against heat-shock proteins may lead to autoimmunity, as illustrated by adjuvant arthritis in Lewis rats. Current evidence also points towards a role of T cell immunity against heat-shock proteins in the development of human autoimmune diseases such as juvenile chronic arthritis.

Animals↗