Soniya Nityanand
AB STRACT
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 susequent 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 proppensity 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
clearence of hepatitis Ags/genome from serum and CICs
