Goodpasture's autoimmune disease — A collagen IV disorder

Pedchenko, Vadim; Kitching, A. Richard; Hudson, Billy G.

doi:10.1016/j.matbio.2018.05.004

Cited by 30 publications

(33 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The lung vasculature accommodates the entire cardiac output, allowing almost all RBCs to pass through the alveolar capillaries in order to be loaded with oxygen. Conditions that affect alveolar capillary integrity/permeability (e.g., Goodpasture’s disease) [106] can lead to hemorrhage into the alveolar space. These patients show alterations in lung iron homeostasis with increased iron levels in alveolar macrophages, likely resulting from hemoglobin-derived iron from phagocytosed RBCs [107].…”

Section: Lung Iron Homeostasismentioning

confidence: 99%

Iron Homeostasis in the Lungs—A Balance between Health and Disease

et al. 2019

View full text Add to dashboard Cite

A strong mechanistic link between the regulation of iron homeostasis and oxygen sensing is evident in the lung, where both systems must be properly controlled to maintain lung function. Imbalances in pulmonary iron homeostasis are frequently associated with respiratory diseases, such as chronic obstructive pulmonary disease and with lung cancer. However, the underlying mechanisms causing alterations in iron levels and the involvement of iron in the development of lung disorders are incompletely understood. Here, we review current knowledge about the regulation of pulmonary iron homeostasis, its functional importance, and the link between dysregulated iron levels and lung diseases. Gaining greater knowledge on how iron contributes to the pathogenesis of these diseases holds promise for future iron-related therapeutic strategies.

show abstract

Section: Lung Iron Homeostasismentioning

confidence: 99%

Iron Homeostasis in the Lungs—A Balance between Health and Disease

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Since e.g., laminins, entactin, collagens, and other ligands are obligate constituents in all basement membranes, this is relevant also for basement membranes in glomeruli [discussed in ( 11 )], alveoli ( 187 ) and skin ( 188 ). Accordingly, one would expect affection of glomeruli ( Figure 5A ), alveoli ( Figure 5B ) and also skin ( Figure 5C ) in analogy to Goodpasture syndrome [glomerulonephritis and alveolitis ( 189 , 190 )], and to autoimmune skin diseases ( 191 – 193 , 197 ). Surprisingly, in context of studies on the impact of cross-reactive anti-dsDNA antibodies as central in the pathogenesis of lupus nephritis, the involvement in other organs has not been considered in relevant studies.…”

Section: Anti-dsdna Antibodies and Lupus Nephritismentioning

confidence: 99%

Autoimmunity and SLE: Factual and Semantic Evidence-Based Critical Analyses of Definitions, Etiology, and Pathogenesis

Rekvig

2020

Front. Immunol.

View full text Add to dashboard Cite

One cannot discuss anti-dsDNA antibodies and lupus nephritis without discussing the nature of Systemic lupus erythematosus (SLE). SLE is insistently described as a prototype autoimmune syndrome, with anti-dsDNA antibodies as a central biomarker and a pathogenic factor. The two entities, “SLE” and “The Anti-dsDNA Antibody,” have been linked in previous and contemporary studies although serious criticism to this mutual linkage have been raised: Anti-dsDNA antibodies were first described in bacterial infections and not in SLE; later in SLE, viral and parasitic infections and in malignancies. An increasing number of studies on classification criteria for SLE have been published in the aftermath of the canonical 1982 American College of Rheumatology SLE classification sets of criteria. Considering these studies, it is surprising to observe a nearby complete absence of fundamental critical/theoretical discussions aimed to explain how and why the classification criteria are linked in context of etiology, pathogenicity, or biology. This study is an attempt to prioritize critical comments on the contemporary definition and classification of SLE and of anti-dsDNA antibodies in context of lupus nephritis. Epidemiology, etiology, pathogenesis, and measures of therapy efficacy are implemented as problems in the present discussion. In order to understand whether or not disparate clinical SLE phenotypes are useful to determine its basic biological processes accounting for the syndrome is problematic. A central problem is discussed on whether the clinical role of anti-dsDNA antibodies from principal reasons can be accepted as a biomarker for SLE without clarifying what we define as an anti-dsDNA antibody, and in which biologic contexts the antibodies appear. In sum, this study is an attempt to bring to the forum critical comments on the contemporary definition and classification of SLE, lupus nephritis and anti-dsDNA antibodies. Four concise hypotheses are suggested for future science at the end of this analytical study.

show abstract

“…The pathophysiology of Alport Syndrome consists of structural defects in type IV collagen alpha chains that constitutes the glomerular basement membrane [2][3]. Collagen type IV are encoded by six distinct genes (COL4A1 to COL4A6) consisting of six alpha chains (α1-α6) which assemble in heterotrimers (three α chains coiled together) forming a protomer [4][5]. There are three major mutations in α3, α4 or α5 generating defective type IV collagen networks and preventing proper structure of glomerular basement membrane [6][7].…”

Section: Introductionmentioning

confidence: 99%

“…The α1α1α2 (IV) protomer is ubiquitously distributed in all basement membranes during embryogenesis, later are replacing by the protomer α3α4α5 (IV) in glomerular basement membrane and protomer α5α5α6 in other tissues [13]. The α3α4α5 (IV) is known to be more cross-linked protomer [14][15], resulting in a stronger and more resistant heterotrimer [16] Collagen IV network has a crucial role for development of glomerular basement membrane during ontogenesis, which helps to support tissue integrity besides cell signaling, morphogenesis and tissue regeneration [4]. There is an interaction in the biogenesis of collagen produced by podocytes and the glomerular basement membrane.…”

Section: Introductionmentioning

confidence: 99%

Novel Variants in COL4A3 and COL4A4 are Causes of Alport Syndrome in Rio Grande do Norte, Brazil

Uchôa

et al. 2019

Preprint

View full text Add to dashboard Cite

Background. Alport syndrome is a progressive and hereditary nephropathy, characterized by hematuria and proteinuria, and extrarenal manifestations as hearing loss and eye abnormalities. The disease can be expressed as autosomal recessive or dominant, caused by variants in COL4A3 and COL4A4 loci, respectively, or X-linked caused by variants in COL4A5 locus.Methods. Two unrelated families with Alport Syndrome from northeast of Brazil were studied and whole exome sequencing were performed. DNA sequences were mapped against the human genome (GRCh38/hg38 build) to identify associated mutations.Results. Variant analysis showed deleterious variants in COL4A3 and COL4A4 loci in chromosome 2. Two variants were detected with alternative alleles in a homozygous state in the probands. One novel premature stop codon at position 481 of COL4A3 protein is present in one family and one frameshift mutation leading to a premature stop codon at position 786 of COL4A4 protein in the other family. Both Alport cases presented their variants surrounded by a broad runs of homozygosity (ROH). Conclusions. The autosome recessive inheritance coupled with the runs of homozygosity in both families suggest inbreeding. 7. Iozzo R V., Gubbiotti MA. Extracellular matrix: The driving force of mammalian diseases. 13. Ninomiya Y, Kagawa M, Iyama KI, et al. Differential expression of two basement membrane collagen genes, COL4A6 and COL4A5, demonstrated by immunofluorescence staining using peptide-specific monoclonal antibodies.

show abstract

Goodpasture's autoimmune disease — A collagen IV disorder

Cited by 30 publications

References 103 publications

Iron Homeostasis in the Lungs—A Balance between Health and Disease

Iron Homeostasis in the Lungs—A Balance between Health and Disease

Autoimmunity and SLE: Factual and Semantic Evidence-Based Critical Analyses of Definitions, Etiology, and Pathogenesis

Novel Variants in COL4A3 and COL4A4 are Causes of Alport Syndrome in Rio Grande do Norte, Brazil

Contact Info

Product

Resources

About