Our laboratory has two areas of research:
- Focusing on the immunogenetic as well as immunopathogenic
events in relapsing polychondritis.
- Focusing on the role of microbial agents in susceptibility/resistance
to the onset of arthritis.
Experimental Polychondritis
Relapsing polychondritis (RP) is a human autoimmune disease
of unknown etiology first described in 1923 by Jaksch-Wartenhorst
and is characterized most commonly by the presence of
auricular chondritis (in over 90% of RP patients over
the course of disease) and polyarthritis (in approximately
50% of RP patients). To a lesser extent, RP patients also
display nasal, ocular, respiratory track, cardiovascular,
central nervous system, and kidney involvement. During
the cyclic inflammatory episodes that occur in RP there
is extensive infiltration of the cartilaginous portions
of the affected sites by mononuclear cells including lymphocytes,
macrophages, and eosinophils. Type II collagen specific
antibodies and T cells have both been detected in sera
of RP patients which has lead to the suggestion that type
II collagen may be a putative autoantigen in the induction
of RP. While there is no known genetic linkage between
RP and specific alleles of HLA-A or B, an association
between susceptibility to RP and HLA-DR4 expression, 56%
compared to 26% of RP patients and healthy controls, respectively,
expressed at least one DR4 allele has been reported. Surprisingly,
there was no difference in the frequency of DRB1*04 subtypes
between RP patients and controls.
Time course of auricular chondritis in experimental
polychondritis - Chondritic ears from DQ6a
b 8a b tg mice representing disease at one
and four weeks after the onset are shown in Panels B and
C, respectively, compared to a healthy DQ6a b
8a b ear (Panel A). Bilateral swelling and erythema
of the cartilaginous regions of the outer ear accompany
the onset of auricular chondritis. This is followed by
the atrophy of the outer ear and the "cauliflower"
appearance.
We have recently described an experimental polychondritis
that occurs only in transgenic mice expressing certain
combinations of human HLA molecules following type II
collagen immunization mirrors many manifestations of human
RP and provides a unique tool with which we are studying
the immunogenetic as well as immunopathologic events that
occur during polychondritis.
Histological analysis of chondritic ears during experimental
polychondritis. - A section of a chondritic ear, 4
weeks after onset (A) compared to a healthy ear (B) of
DQ6a b 8a b tg mice, stained with hematoxylin
and eosin and magnified X 50. During auricular chondritis
there is a significant infiltration of mononuclear cells
and the destruction of the cartilaginous tissues.
Natural Adjuvants
A role for concurrent or previous bacteria or viral infection
in the onset of human rheumatoid arthritis has been postulated
for many years. While the potential for molecular mimicry
has been highly investigated, the immunostimulatory affect
of concurrent infection are less well understood. We are
investigating the influence of concurrent infection of
various Gram negative bacteria on an animal model of human
rheumatoid arthritis, collagen induced arthritis.
