Immune mechanisms in vasculopathies

Most of the inflammatory vasculopathies, termed as vasculitides are considered to be mediated at least in part by immunopathogenic mechanisms. With the recent demonstration of immune cells in atherosclerotic plaques, immune mechanisms are considered to play an important role in atherosclerotic vasculopathies too. The main components involved in the immune-mediated vascular injury are immune complexes, antibodies to vascular wall antigens and T cells. These components may be involved singly or in consort to each other in a particular disease state. The aims of the present study were to investigate the role of (a) T cells in 2 groups of vasculitides - Wegener's granulomatosis (WG) and Takayasu's arteritis (TA); (b) anti-cardiolipin (ACLA) and anti-endothelial cell antibodies (AECA) in TA; (c) ACLA, AECA and circulating immune complexes (CICs) in myocardial infarction and in early onset atherosclerosis of peripheral vasculature; (d) CICs in vasculitis associated with hepatitis B and C infections and the role of anti-viral therapy in such cases.

In both WG and TA, there were expanded populations of different AV/BV TCR bearing peripheral blood T cells. In WG a number of these had dramatic magnitudes. The expanded populations were HLA DR+, CD25+, CD28+ and either CD45RA+ or RO+. In WG, a more detailed study of the expanded populations showed them to persist in an activated state and in same magnitude for the total observation time of 28-38 months, irrespective of the disease going into clinical remission. Functionally the expanded populations were activated. These populations expressed and secreted the studied cytokines IL-2, IL-4, IFNy and GM-CSF. The activated status and secretion of cytokines by the expanded populations shows their involvement in the pathogenesis of WG. Most of the expanded populations were clonal and a further study would help in the elucidation of the inciting antigen.

A higher prevalence of ACLA and AECA was observed in TA patients with a correlation with disease activity. A higher prevalence of ACLA and AECA was also observed in MI and peripheral atherosclerosis patients. A significant observation was that the levels of IgG and IgA ACLA at 50 years of age were predictive of the subsequent occurrence of MI between 50-70 years of age and mortality related to it, independent of other conventional risk factors. Fifty % of peripheral atherosclerosis patients had CICs with a propensity for those with C4 null alleles to have CICs.

All the 7 patients with vasculitis associated with hepatitis B and C infections had high levels of CICs/cryoglobulins containing hepatitis Ags/Abs/genome. With anti-viral therapy all the 7 patients showed a rapid clinical improvement in the vasculitis and a concomitant sharp decline in CICs/cryoglobulins. 6 patients went into long lasting remissions with clearance of hepatitis Ags/genome from serum and CICs.