The origin and activities of IgA1-containing immune complexes in IgA nephropathy
IgA nephropathy is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgA nephropathy is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or co-dominant IgA-containing immunodeposit...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00117/full |
| _version_ | 1818024528182247424 |
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| author | Barbora eKnoppova Colin eReily Nicolas eMaillard Dana V. Rizk Zina eMoldoveanu Jiri eMestecky Milan eRaska Milan eRaska Matthew B. Renfrow Bruce A. Julian Jan eNovak |
| author_facet | Barbora eKnoppova Colin eReily Nicolas eMaillard Dana V. Rizk Zina eMoldoveanu Jiri eMestecky Milan eRaska Milan eRaska Matthew B. Renfrow Bruce A. Julian Jan eNovak |
| author_sort | Barbora eKnoppova |
| collection | DOAJ |
| description | IgA nephropathy is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgA nephropathy is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or co-dominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with variable presence of IgG and/or IgM. The IgA in these renal deposits is galactose-deficient IgA1, with less than a full complement of galactose residues on the O-glycans in the hinge region of the heavy chains. Research from the past decade led to the definition of IgA nephropathy as an autoimmune disease with a multi-hit pathogenetic process with contributing genetic and environmental components. In this process, circulating galactose-deficient IgA1 (autoantigen) is bound by anti-glycan IgG or IgA (autoantibodies) to form immune complexes. Some of these circulating complexes deposit in glomeruli, and thereby activate mesangial cells and induce renal injury through cellular proliferation and overproduction of extracellular matrix components and cytokines/chemokines. Glycosylation pathways associated with production of the autoantigen and the unique characteristics of the corresponding autoantibodies in patients with IgA nephropathy have been uncovered. Complement likely plays a significant role in the formation and the nephritogenic activities of these complexes. Complement activation is mediated through the alternative and lectin pathways and probably occurs systemically on IgA1-containing circulating immune complexes as well as locally in glomeruli. Incidence of IgA nephropathy varies greatly by geographical location; the disease is rare in central Africa but accounts for up to 40% of native-kidney biopsies in eastern Asia. Some of this variation may be explained by genetically determined influences on the pathogenesis of the disease. Genome-wide association studies to date have identified 18 risk loci associated with IgA nephropathy. Some of these loci are associated with increased prevalence of IgA nephropathy, whereas others contain alterations, such as deletion of complement factor H-related genes 1 and 3, that are protective against the disease. Understanding the molecular mechanisms and genetic and biochemical factors involved in formation and activities of pathogenic IgA1-containing immune complexes will enable development of future disease-specific therapies as well as identification of noninvasive disease-specific biomarkers. |
| first_indexed | 2024-12-10T04:01:39Z |
| format | Article |
| id | doaj.art-dae41546706a4fd58571e88812d8dd13 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T04:01:39Z |
| publishDate | 2016-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dae41546706a4fd58571e88812d8dd132022-12-22T02:02:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-04-01710.3389/fimmu.2016.00117188079The origin and activities of IgA1-containing immune complexes in IgA nephropathyBarbora eKnoppova0Colin eReily1Nicolas eMaillard2Dana V. Rizk3Zina eMoldoveanu4Jiri eMestecky5Milan eRaska6Milan eRaska7Matthew B. Renfrow8Bruce A. Julian9Jan eNovak10University of Alabama at BirminghamUniversity of Alabama at BirminghamUniversité Jean Monnet, Saint Etienne, PRES Université de Lyon,University of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamFaculty of Medicine and Dentistry, Palacky University and University HospitalUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamUniversity of Alabama at BirminghamIgA nephropathy is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgA nephropathy is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or co-dominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with variable presence of IgG and/or IgM. The IgA in these renal deposits is galactose-deficient IgA1, with less than a full complement of galactose residues on the O-glycans in the hinge region of the heavy chains. Research from the past decade led to the definition of IgA nephropathy as an autoimmune disease with a multi-hit pathogenetic process with contributing genetic and environmental components. In this process, circulating galactose-deficient IgA1 (autoantigen) is bound by anti-glycan IgG or IgA (autoantibodies) to form immune complexes. Some of these circulating complexes deposit in glomeruli, and thereby activate mesangial cells and induce renal injury through cellular proliferation and overproduction of extracellular matrix components and cytokines/chemokines. Glycosylation pathways associated with production of the autoantigen and the unique characteristics of the corresponding autoantibodies in patients with IgA nephropathy have been uncovered. Complement likely plays a significant role in the formation and the nephritogenic activities of these complexes. Complement activation is mediated through the alternative and lectin pathways and probably occurs systemically on IgA1-containing circulating immune complexes as well as locally in glomeruli. Incidence of IgA nephropathy varies greatly by geographical location; the disease is rare in central Africa but accounts for up to 40% of native-kidney biopsies in eastern Asia. Some of this variation may be explained by genetically determined influences on the pathogenesis of the disease. Genome-wide association studies to date have identified 18 risk loci associated with IgA nephropathy. Some of these loci are associated with increased prevalence of IgA nephropathy, whereas others contain alterations, such as deletion of complement factor H-related genes 1 and 3, that are protective against the disease. Understanding the molecular mechanisms and genetic and biochemical factors involved in formation and activities of pathogenic IgA1-containing immune complexes will enable development of future disease-specific therapies as well as identification of noninvasive disease-specific biomarkers.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00117/fullAutoantibodiesComplement C3IgAimmune complexesnephropathy |
| spellingShingle | Barbora eKnoppova Colin eReily Nicolas eMaillard Dana V. Rizk Zina eMoldoveanu Jiri eMestecky Milan eRaska Milan eRaska Matthew B. Renfrow Bruce A. Julian Jan eNovak The origin and activities of IgA1-containing immune complexes in IgA nephropathy Frontiers in Immunology Autoantibodies Complement C3 IgA immune complexes nephropathy |
| title | The origin and activities of IgA1-containing immune complexes in IgA nephropathy |
| title_full | The origin and activities of IgA1-containing immune complexes in IgA nephropathy |
| title_fullStr | The origin and activities of IgA1-containing immune complexes in IgA nephropathy |
| title_full_unstemmed | The origin and activities of IgA1-containing immune complexes in IgA nephropathy |
| title_short | The origin and activities of IgA1-containing immune complexes in IgA nephropathy |
| title_sort | origin and activities of iga1 containing immune complexes in iga nephropathy |
| topic | Autoantibodies Complement C3 IgA immune complexes nephropathy |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00117/full |
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