In contrast, other studies showed that serum levels did not significantly differ (i) between IgAVwithoutnephritis (likely what we now call skin-limited IgAV) and healthy controls (12,23) or (ii) between children with IgAV and children with inactive IgAV-nephritis or with controls (12). == 3.2. reasons for increased generation of immunoglobulins or formation of IC and their perivascular deposition in either skin or systemic organs are different and not fully explored. A common denominator of OC vasculitides is the activation of PMNs near the vessel wallviaFcy or Fc receptors. Acute episodes of IgAV additionally require PMNs to become preactivated by IgA1 or by IC already in circulation. This intravascular priming results in increased adherence and subsequently vessel-destructive NETosis when they encounter IgA deposited at the vessel walls. Binding of IgA1 to PMNs in blood stream is usually associated with increased serum levels ABT-888 (Veliparib) of hypogalactosidated IgA1. The characteristic clinical picture of IgAV (and also of so-called IgG/IgM vasculitis) comprises palpable or retiform purpura with a clear predilection for lower legs, probably due to stasis-related reduction in blood velocity, ABT-888 (Veliparib) while in other IC vasculitides, additional factors influence the sites of vasculitides. Our knowledge of distinct forms and different pathophysiological pathways of IC vasculitides may lead to in efficacious or targeted therapies. Antibodies to complement components or intestinal budesonide for IgAV are promising agents (the latter suppresses the pathophysiologically related IgA nephropathy by reducing the generation of mucosal IgA. Keywords:IgA vasculitis, cryoglobulinemic vasculitis, rheumatoid vasculitis, hypocomplementaemic vasculitis, serum sickness, glomerulonephritis IgA1, cutaneous IgM/IgG-vasculitis, immune complex disease == 1. Definition and different forms of immune complex vasculitides == Immune complex vasculitides present inflammations of vessel walls associated with and mainly elicited by perivascular deposition of immunoglobulins, mostly in the form of immune complexes (ICs). There are different forms of immune complex vasculitides (Table 1) (1): systemic and skin-limited variants (1) of IgA vasculitis (IgAV) (Physique 1), cryoglobulinemic vasculitis (CV), rheumatoid vasculitis (RV), lupus vasculitis (LE vasculitis), hypocomplementemic vasculitis (Physique 2), and ABT-888 (Veliparib) serum sickness, as well as the provisionally defined forms of cutaneous IgM/IgG immune complex vasculitides and a recurrent macular vasculitis induced by hypergammaglobulinemia (Waldenstrm) (Physique 3) or by exertion or heat, or a, vasculitis in gammopathy other than cryoglobulinemic vasculitis (2,3). == Table 1. == Immune complex vasculitides. == Physique 1. == Round or oval and retiform (or branched) palpable purpura in IgA vasculitis. == Physique 2. ABT-888 (Veliparib) == Cutaneous hypocomplementemic IgG/IgM-vasculitis. == Physique 3. == Recurrent macular vasculitis ABLIM1 associated with hypergammaglobulinemia and induced by exertion. According to Coombs and Gell, the so-called type III hypersensitivity reaction has been considered among immunologists as a model for immune complex vasculitis. The prototype would have been that of serum sickness that occurs when a certain antigen in the circulation encounters approximately equimolar concentrations of fitting antibodies (4,5) so that large lattices of circulating immune complexes form, which subsequently become deposited at the walls of small blood vessels, where they activate the complement system and polymorphonuclear neutrophils (PMNs). This disease has has long been considered to present the primary example for immune complex vasculitis and corresponding animal models, including the Arthus reaction, and has largely dominated ABT-888 (Veliparib) the pathophysiological concept of immune complex disease in general and immune complex vasculitis in particular. However, the pathophysiology of IgA vasculitis has been revealed to differ at least in its initial stages from serum sickness, because it is usually primarily the altered galactosidation of the IgA1 molecule which mediates its deposition at certain vasculatures and not the size of the IC (6,7). Circulating complexes have also been demonstrated to present a major pathophysiological factor for vasculitis in cryoglobulinemia and in rheumatoid arthritis (RA) (1). Common denominators for immune complex vascultides are perivascular deposition of altered immunoglobulins or immune complexes, and their subsequent full activation of PMNs close to the vessel wallviaFcyR or FcR. Histologically, the resulting picture of small vessel vasculitis is generally that of leukocytoclastic vasculitis of post-capillary venules, which.