Autoantibodies to Pancreatic hsp60 Precede the Development of Glucose Intolerance in Patients with Cystic Fibrosis

Jensen, Peter Kjær Mackie; Johansen, Helle Krogh; Carmi, Pnina; Høiby, Niels; Cohen, Irun R.

doi:10.1006/jaut.2001.0532

Cited by 22 publications

(17 citation statements)

References 24 publications

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“…Increased prevalence involves older individuals, but CFRD has been diagnosed in even younger patients, as HLA class II (37) or VNTR (29), but, as in DM type 2, a correlation has been found with genes linked with the tumor necrosis factor (37), heat shock protein (37,38), and calpain 10 (39). Occasionally, DM type 1 has been found in CF (40,41).…”

Section: Incidence and Prevalencementioning

confidence: 99%

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD)

Noronha

Calliari

Damaceno

et al. 2011

Arq Bras Endocrinol Metab

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Cystic fibrosis (CF) is the most common recessive autosomal disease among Caucasian. Children with CF have benefitted from advances in medical and nutritional treatments, and this can be gleaned from the improvement in the survival of these patients. The increase in the survival rate brought with it the appearance of co-morbidities related to CF. Nowadays cystic fibrosis-related diabetes (CFRD) is considered the most common complication associated with CF. It can appear as early as infancy or adolescence, and its prevalence can be as high as 50% in adult patients. Because of its high prevalence, difficulties in early detection and the risks involved, in recent years several studies and consensuses have focused on this condition, adding information about the epidemiology, pathophysiology, prognosis and treatment of CFRD. The main aspects of these new concepts, as well as the current recommendations for its diagnosis and follow-up, will be presented in this study.

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Section: Incidence and Prevalencementioning

confidence: 99%

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD)

Noronha

Calliari

Damaceno

et al. 2011

Arq Bras Endocrinol Metab

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“…Both HSPs are highly immunogenic and capable of inducing antibody production and T cell activation. HSP60, an endogenous ligand for the TLR4 receptor, has been implicated in inflammatory conditions such as Type 1 diabetes in CF patients (52). Higher levels of serum IgG antibodies against HSP27, HSP60, and HSP90 (HSP84 homologue) have been detected in CF patients than in non-CF patients (53,54).…”

Section: Cftr Interactome Comparison In Ib3-1 Cell Lines With Other Cmentioning

confidence: 99%

Chemical Rescue of c:\working\Bhatia\2020\08-aug\asmb\upload\j-elbm0001-0142F508-CFTR Mimics Genetic Repair in Cystic Fibrosis Bronchial Epithelial Cells

Singh¹,

Pollard

Zeitlin³

2008

Molecular & Cellular Proteomics

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In a previous study of sodium 4-phenylbutyrate (4-PBA)-responsive proteins in cystic fibrosis (CF) IB3-1 bronchial epithelial cells, we identified 85 differentially expressed high abundance proteins from whole cellular lysate (Singh, O. V., Vij, N., Mogayzel, P. J., Jr., Jozwik, C., Pollard, H. B., and Zeitlin, P. L. (2006) Pharmacoproteomics of 4-phenylbutyrate-treated IB3-1 cystic fibrosis bronchial epithelial cells. J. Proteome Res. 5, 562-571). In the present work we hypothesize that a subset of heat shock proteins that interact with cystic fibrosis transmembrane conductance regulator (CFTR) in common during chemical rescue and genetic repair will identify therapeutic networks for targeted intervention. Immunocomplexes were generated from total cellular lysates, and three subcellular fractions (endoplasmic reticulum (ER), cytosol, and plasma membrane) with anti-CFTR polyclonal antibody from CF (IB3-1), chemically rescued CF (4-PBA-treated IB3-1), and genetically repaired CF (IB3-1/S9 daughter cells repaired by gene transfer with adeno-associated virus-(wild type) CFTR). CFTR-interacting proteins were analyzed on two-dimensional gels and identified by mass spectrometry. A set of 16 proteins known to act in ER-associated degradation were regulated in common and functionally connected to the protein processing, protein folding, and inflammatory response. Some of these proteins were modulated exclusively in ER, cytosol, or plasma membrane. A subset of 4-PBA-modulated ER-associated degradation chaperones (GRP94, HSP84, GRP78, GRP75, and GRP58) was observed to associate with the immature B form of CFTR in ER. HSP70 and HSC70 interacted with the C band (mature form) of CFTR at the cell surface. We conclude that chemically rescued CFTR associates with a specific set of HSP70 family proteins that mark therapeutic interactions and can be useful to correct both ion transport and inflammatory phenotypes in CF subjects.

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“…There does not appear to be a correlation with known T1D susceptibility genes such as HLA class II [20] or insulin VNTR [17], but a possible link has been described between CFRD and T2D susceptibility genes associated with inflammation such as the genes encoding tumor necrosis factor [20], heat shock protein [20,21] and calpain 10 [22]. …”

Section: Pathophysiology Of Cfrdmentioning

confidence: 99%

Cystic Fibrosis-Related Diabetes in Childhood

2010

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Since the early 1990s the management of children with cystic fibrosis (CF) has come a long way and advances in both nutritional and medical care have resulted in a median age of survival of 30–35 years, as compared with a life expectancy of <1 year in the 1950s. The first definitive reports of glucose intolerance or diabetes in CF are from 1955. The combination of CF and related diabetes (CFRD) has a negative impact on survival. CFRD is now the most common complication of CF (50% of the CF patients will develop diabetes by the age of 30 years), and is associated with a 6-fold increase in morbidity and mortality. CFRD is usually asymptomatic and can remain undetected for up to 4 years prior to diagnosis. The objective of this report was to review the current literature (Medline and Pubmed searches) on CFRD in children and adolescents and provide a comprehensive report of incidence, prevalence and pathophysiology of insulin deficiency and insulin insensitivity. Along with survival and prognosis in CFRD the current management strategies in the diagnosis, monitoring and treatment of CFRD will also be addressed.

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Autoantibodies to Pancreatic hsp60 Precede the Development of Glucose Intolerance in Patients with Cystic Fibrosis

Cited by 22 publications

References 24 publications

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD)

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD)

Chemical Rescue of c:\working\Bhatia\2020\08-aug\asmb\upload\j-elbm0001-0142F508-CFTR Mimics Genetic Repair in Cystic Fibrosis Bronchial Epithelial Cells

Cystic Fibrosis-Related Diabetes in Childhood

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