Autoantibodies against chaperonin CCT in human sera with rheumatic autoimmune diseases: comparison with antibodies against other Hsp60 family proteins

Yokota, Shinichi; Hirata, Daisuke; Minota, Seiji; Higashiyama, Takanobu; Kurimoto, Masashi; Yanagi, Hideki; Yura, Takashi

doi:10.1379/1466-1268(2000)005<0337:aaccih>2.0.co;2

Cited by 61 publications

(52 citation statements)

References 47 publications

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“…[52][53][54][55] What we present here, in this work, is another, distinct aspect of Hsp60 involvement in pathogenesis. Our data pertain to a different mechanism in which Hsp60 does not act as autoantigen but as an immune-system signal factor that triggers components of the innate immune response, leading to inflammation rather than to antibody production.…”

Section: Discussionmentioning

confidence: 99%

Changes in Immunohistochemical Levels and Subcellular Localization After Therapy and Correlation and Colocalization With CD68 Suggest a Pathogenetic Role of Hsp60 in Ulcerative Colitis

Tomasello

Rodolico²,

Zerilli³

et al. 2011

Applied Immunohistochemistry &Amp; Molecular Morphology

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Abstract:In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed that Hsp60Fclassically a mitochondrial proteinFwas abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease.

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Section: Discussionmentioning

confidence: 99%

Changes in Immunohistochemical Levels and Subcellular Localization After Therapy and Correlation and Colocalization With CD68 Suggest a Pathogenetic Role of Hsp60 in Ulcerative Colitis

Tomasello

Rodolico²,

Zerilli³

et al. 2011

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…In addition it has been recently demonstrated that association of Hsp70 with autoantigens at the dermoepidermal junction can trigger off the production of autoantibodies against Hsp in Mrl/Mplpr/lpr mice and in SLE patients (11,12). Such anti-Hsp production would result in a cross-reactivity to nuclear extractable autoantigens-complexed with Hsp, notwithstanding further investigations are necessary to clarify this hypothesis (13,14). Overall the pathogenic role of Hsp in the immunopathology of lupus skin is still under discussion (15)(16).…”

Section: Discussionmentioning

confidence: 99%

Possible role of Hsp70 in autoantigens shuttling to dermo-epidermal junction in systemic lupus erythematosus

Villalobos-Hurtado¹,

Sh²,

Avalos‐Díaz³

et al. 2011

Reumatismo

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RIASSUNTO La formazione di depositi di materiale immune lungo la giunzione dermo-epidermica nei pazienti affetti da lupus eritematoso sistemico (LES), è il risultato dall'interazione in situ degli anticorpi antinucleari con i loro rispettivi antigeni. L'esposizione al sole determina la liberazione di autoantigeni cutanei e simultaneamente la produzione di heat shock proteins (Hsp). In questo studio abbiamo valutato mediante immunofluorescenza la presenza di Hsp70 lungo la giunzione dermo-epidermica in 20 biopsie cutanee di pazienti affetti da LES ed in 20 soggetti di controllo. I depositi immuni cutanei erano pricipalmente composti da IgG, IgM e C3. Tali depositi sono stati evidenziati lungo la giunzione dermo-epidermica in tutte le biopsie dei pazienti affetti da LES. Erano inoltre evidenti depositi di materiale immune nei vasi cutanei ed in misura minore nei keratinociti epidermici. La presenza di Hsp70 è stata evidenziata nel 60% delle biopsie dei pazienti affetti da LES. Questa proteina era pricipalmente distribuita lungo la giun-view that Hsp are induced in the skin after sun exposure, we theorized that Hsp would shuttle autoantigens to the dermo-epidermal junction. To assess our hypothesis the presence of Hsp70 concurrent with lupus band immunoreagents was studied in skin biopsies from lupus patients. MATERIAL AND METHODSPatients. Twenty patients (18 females and 2 males; mean age 23 years, range 16-35 years) with systemic lupus erythematosus diagnosed according to ACR classification criteria were studied (6). Skin biopsies were performed after informed consent had been obtained. Twenty biopsies taken from the skin of the back of healthy individuals during orthopaedic surgery were used as controls.Skin Biopsies. Samples were obtained from non-lesional and unexposed skin using a 5 mm punch, under local anaesthesia with 1% xilocaine (Astra). The biopsies were rinsed in 0.15 M NaCl pH 7.5 buffer solution (PBS), and immediately included in Tissue-Tek (Ames), and frozen at -20°C. The specimens were then cryosectioned at 4 µm, and used for immunofluorescent assays. Direct immunofluorescence (IF). Skin biopsies were examined by IF as follows: 4 µm skin sections were fixed in cold acetone, washed in PBS and incubated 30 minutes with monospecific goat anti human-IgG, IgA, IgM, C3, C4, C1q and fibrinogen antibodies (Sigma. St Louis MO). After washings with PBS, the slides were evaluated using an Olympus B-Max microscope equipped with epifluorescence. Controls were processed equally. Double labelling Assay. Skin sections were incubated with FITC (green tagged) monospecific anti-IgG, IgA and IgM antibodies; after washing the slides were incubated with a monoclonal antiHsp70 antibody (Sigma); next, specimens were washed and reincubated with a second antibody tagged in red (rabbit anti-mouse rodamin conjugated IgG) to disclose the Hsp70. Fluorescein and rodamine filter combinations were used, with excitations of 488 and 546 nm and emissions of 520 and 568 nm respectively. RESULTS Patients.None of SLE patients were under ...

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“…Sandwich enzyme-linked immunosorbent assay for determining HSP47 concentration Sandwich enzyme-linked immunosorbent assay for determining HSP47 concentration was carried out as described previously (Yokota et al 2000(Yokota et al , 2003. Serum levels of HSP47 were measured in all enrolled patients.…”

Section: Study Populationmentioning

confidence: 99%

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

Kakugawa

Yokota

Ishimatsu

et al. 2013

Cell Stress and Chaperones

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Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic differences involving HSP47 between AE-IPF and stable (S)-IPF. -013-0411-5 and lactate dehydrogenase (LDH) were measured. Immunohistochemical analysis of lung HSP47 expression was determined in biopsy and autopsy tissues diagnosed as diffuse alveolar damage (DAD) and usual interstitial pneumonia (UIP). Serum levels of HSP47 were significantly higher in AE-IPF than in S-IPF patients, whereas serum levels of KL-6, SP-A, and SP-D did not differ significantly. Receiver operating characteristic curves revealed that HSP47 was superior for discriminating AE-IPF and S-IPF. The cutoff for HSP47 resulting in the highest diagnostic accuracy was 559.4 pg/mL; sensitivity, specificity, and diagnostic accuracy were 100.0 %, 93.9 %, and 96.2 %, respectively. Immunohistochemical analysis revealed that pulmonary HSP47 expression was greater in DAD than UIP tissues. Serum HSP47 was significantly higher in AE-IPF than in S-IPF patients, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions.Cell Stress and Chaperones (2013) 18:581-590 DOI 10.1007/s12192

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Autoantibodies against chaperonin CCT in human sera with rheumatic autoimmune diseases: comparison with antibodies against other Hsp60 family proteins

Cited by 61 publications

References 47 publications

Changes in Immunohistochemical Levels and Subcellular Localization After Therapy and Correlation and Colocalization With CD68 Suggest a Pathogenetic Role of Hsp60 in Ulcerative Colitis

Changes in Immunohistochemical Levels and Subcellular Localization After Therapy and Correlation and Colocalization With CD68 Suggest a Pathogenetic Role of Hsp60 in Ulcerative Colitis

Possible role of Hsp70 in autoantigens shuttling to dermo-epidermal junction in systemic lupus erythematosus

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis

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