Henoch-Schönlein purpura pathophysiology
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Henoch-Schönlein purpura (HSP) is an immune complex-mediated disease with circulating immune complexes and IgA rheumatoid factors usually follows upper respiratory tract infections, various viruses, and the bacteria have been implicated as triggers of the disease.
- HSP is a small vessel leukocytoclastic vasculitis, but its pathophysiology is not completely understood.
- In patients with HSP the serum IgA levels are elevated, HSP is an immune complex-mediated disease with circulating immune complexes and IgA rheumatoid factors usually follows upper respiratory tract infections, various viruses, and the bacteria have been implicated as triggers of the disease.
- Patients with HSP have circulating IgA immune-complexes, patients with HSPN have an additional large molecular mass IgA1-IgG-containing circulating immune complexes.
- The IgA1 molecule has a hinge region containing up to six O-linked glycan chains consisting of N-acetylgalactosamine, usually with an attached β1,3-linked galactose.
- It has been reported that in patients with HSP, the activity of β1,3-galactosyltransferase in peripheral B cells is reduced, leading to a lack of terminal β1,3-galactosyl residues in the hinge region of IgA1.
- The primary defect leading to the production of such abnormally glycosylated IgA1 is probably heritable.
- These aberrantly glycosylated IgA1 molecules have been shown to form immune complexes with IgG antibodies specific for galactose-deficient IgA1, thereby inhibiting the binding of the IgA molecules to hepatic receptors and avoiding their internalization and degradation by hepatic cells.
- This formation results in an increased amount of IgA immune complexes in circulation.
- The complexes may then deposit in renal mesangial areas and activate the complement system by the alternative or lectin pathways, which play a major role in the pathophysiology of this disease.
- Further, after depositing in the mesangium, the galactose-deficient IgA1 immune complexes activate mesangial cells.
- This results in the proliferation of cells such as macrophages and lymphocytes and the production of inflammatory and profibrogenic cytokines and chemokines, which play a pivotal role in mesangial cell proliferation, matrix expansion, and inflammatory cell recruitment.
- Other mechanisms for developing HSP
- Light Microscopy
- IgA deposition in postcapillary venules with IgA deposition and leukocytoclastic vasculitis in is a pathognomonic microscopic feature of Henoch-Schönlein Purpura.
- Skin lesions less than 24 hrs are preferred as the chronic lesion lack the immunoglobulin isotypes essential for the diagnosis of HSP.
- A biopsy from a different skin site is taken for the immunofluorescent studies to confirm the diagnosis.
- IgA deposition in the mesangium on immunofluorescence microscopy should be differentiated from the IgA nephropathy.
- Light microscopic features range from isolated mesangial proliferation to severe crescentic glomerulonephritis.
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