The structure and function of human IgA

Kerr, Michael A.

doi:10.1042/bj2710285

Cited by 509 publications

(422 citation statements)

References 178 publications

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“…IgA1 is unusual in that it has a heavily O-glycosylated hinge region between the CH1 and CH2 domains of the a H chain (1,2). The presence of poorly galactosylated IgA1 O-glycoforms in the serum of patients with IgAN favors formation of circulating immune complexes (IC), which are prone to deposition in the glomerular mesangium (3)(4)(5)(6).…”

mentioning

confidence: 99%

Spleen Tyrosine Kinase Is Important in the Production of Proinflammatory Cytokines and Cell Proliferation in Human Mesangial Cells following Stimulation with IgA1 Isolated from IgA Nephropathy Patients

Kim

McDaid

McAdoo

et al. 2012

The Journal of Immunology

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IgA immune complexes are capable of inducing human mesangial cell (HMC) activation, resulting in release of proinflammatory and profibrogenic mediators. The subsequent inflammation, cellular proliferation, and synthesis of extracellular matrix lead to the progression of IgA nephropathy (IgAN). Spleen tyrosine kinase (SYK) is an intracellular protein tyrosine kinase involved in cell signaling downstream of immunoreceptors. In this study, we determined whether SYK is involved in the downstream signaling of IgA1 stimulation in HMC, leading to production of proinflammatory cytokines/chemokines and cell proliferation. Incubation of HMC with IgA1 purified from IgAN patients significantly increased the synthesis of MCP-1 in a dose-dependent manner. There was also significantly increased production of IL-6, IL-8, IFN-γ–inducible protein-10, RANTES, and platelet-derived growth factor-BB. Stimulation of HMC with heat-aggregated IgA1 purified from IgAN patients induced significantly increased HMC proliferation. Both pharmacological inhibition of SYK and knockdown of SYK by small interfering RNA significantly reduced the synthesis of these mediators and inhibited HMC proliferation. Moreover, positive immunostaining for total and phospho-SYK in glomeruli of kidney biopsies from IgAN patients strongly suggests the involvement of SYK in the pathogenesis of IgAN. To our knowledge, we demonstrate, for the first time, the involvement of SYK in the downstream signaling of IgA1 stimulation in HMC and in the pathogenesis of IgAN. Hence, SYK represents a potential therapeutic target for IgAN.

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confidence: 99%

Spleen Tyrosine Kinase Is Important in the Production of Proinflammatory Cytokines and Cell Proliferation in Human Mesangial Cells following Stimulation with IgA1 Isolated from IgA Nephropathy Patients

Kim

McDaid

McAdoo

et al. 2012

The Journal of Immunology

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“…IgA is a major class of immunoglobulin important in mucosal immunity [28], and the glycosylation of IgA1 is important in facilitating the clearance of IgA1 molecules [28]. An abnormal glycosylation of the IgA1 hinge region leads to accumulation of IgA1-dominant macromolecular complexes which activate the alternative complement pathway and result in the recruitment of inflammatory cells [29].…”

Section: Small-vessel Vasculitismentioning

confidence: 99%

Vasculitis: do we know more to classify better?

Batu

Özen

2014

Pediatr Nephrol

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The systemic vasculitides are a heterogeneous group of disorders characterized by the inflammation of blood vessels. The development and implementation of advanced diagnostic tests and genetic studies have resulted in substantial improvement in our understanding of vasculitis pathogenesis, resulting in the revision of the nomenclature and classification for vasculitis. Multicenter, collaborative studies are currently underway to develop improved diagnostic criteria. In this review, the major nomenclature and classification systems for vasculitides are summarized, with special emphasis on those emerging from the recent 2012 Chapel Hill Consensus Conference (CHCC).

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“…Furthermore, there is increasing evidence that many leucocytes have receptors for IgA and binding of IgA to these receptors triggers a variety of effector functions. 25 Similarly, the isotype of rheumatoid factor produced by B-cell lines developed from B-cell populations infiltrating the synovial tissue of patients with advanced rheumatoid arthritis was mostly IgA. 26 In addition, several studies showed raised serum levels of IgA, IgA rheumatoid factor, and IgA-containing circulating immune complexes in rheumatoid arthritis and that IgA rheumatoid factors are produced locally in salivary glands and in synovial tissue.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

Expression of chemokines and gelatinase B in sympathetic ophthalmia

El-Asrar

Struyf

Broeck³

et al. 2006

Eye

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Purpose To examine the expression of gelatinase B (matrix metalloproteinase-9) and the chemokines monocyte chemotactic protein-1 (CCL2/MCP-1) and stromal cell-derived factor-1 (CXCL12/SDF-1) in sympathetic ophthalmia (SO). Methods Five enucleated exciting eyes with a clinical diagnosis and typical histopathological findings of SO were studied by immunohistochemical techniques using a panel of monoclonal antibodies directed against gelatinase B, MCP-1, and SDF-1. In addition, a panel of monoclonal and polyclonal antibodies was used to characterize the composition of the inflammatory infiltrate. Results In all cases, the extensive uveal inflammatory infiltrate was organized as a diffuse infiltrate and as large granulomas consisting of epithelioid cells and multinucleated giant cells. CD20 þ B lymphocytes predominated in the diffuse infiltrate and CD3 þ T lymphocytes were few. The monocyte/macrophage marker CD68 was expressed in scattered inflammatory mononuclear cells and within granulomas and Dalen-Fuchs nodules. Most of the inflammatory cells were HLA-DR þ . Immunoreactivity for gelatinase B, MCP-1, and SDF-1 was observed in cells within granulomas and in scattered epithelioid cells. Immunoreactivity for MCP-1 was noted in retinal pigment epithelial cells. Endothelial cells of choriocapillaries showed weak immunoreactivity for SDF-1. Conclusions Gelatinase B, MCP-1, and SDF-1 might have a pathogenic role in the recruitment of leucocytes into the eye in SO.

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The structure and function of human IgA

Cited by 509 publications

References 178 publications

Spleen Tyrosine Kinase Is Important in the Production of Proinflammatory Cytokines and Cell Proliferation in Human Mesangial Cells following Stimulation with IgA1 Isolated from IgA Nephropathy Patients

Spleen Tyrosine Kinase Is Important in the Production of Proinflammatory Cytokines and Cell Proliferation in Human Mesangial Cells following Stimulation with IgA1 Isolated from IgA Nephropathy Patients

Vasculitis: do we know more to classify better?

Expression of chemokines and gelatinase B in sympathetic ophthalmia

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