Henoch-Schönlein purpura pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
The pathophysiology of HSP:[1][2][3]
- HSP is a small vessel leukocytoclastic vasculitis, but its pathophysiology is not completely understood.
- In patients with HSP the serum Ig-A 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 Ig-A 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.
- There are also other possible pathogenetic mechanisms of HSPN, because throat cultures positive for group A beta-hemolytic streptococcus have been found in 20%-30% of patients with HSPN, it is thought that nephritis-associated plasmin receptor, a group A streptococcal antigen, may also be responsible for some of the cases of HSPN.
- Activation of the eosinophils and expression of the alpha-smooth muscle actin in the kidney also play a vital role in the pathogenesis of Henoch-Schönlein purpura.
References
- ↑ Yang YH, Yu HH, Chiang BL (2014). "The diagnosis and classification of Henoch-Schönlein purpura: an updated review". Autoimmun Rev. 13 (4–5): 355–8. doi:10.1016/j.autrev.2014.01.031. PMID 24424188.
- ↑ Trnka P (December 2013). "Henoch-Schönlein purpura in children". J Paediatr Child Health. 49 (12): 995–1003. doi:10.1111/jpc.12403. PMID 24134307.
- ↑ Rigante D, Castellazzi L, Bosco A, Esposito S (August 2013). "Is there a crossroad between infections, genetics, and Henoch-Schönlein purpura?". Autoimmun Rev. 12 (10): 1016–21. doi:10.1016/j.autrev.2013.04.003. PMID 23684700.