Cartilage proteoglycan‐induced arthritis in BALB/c mice. Antibodies that recognize human and mouse cartilage proteoglycan and can cause depletion of cartilage proteoglycan with little or no synovitis

Abstract

Human fetal cartilage proteoglycan (PG) induces the development of an erosive polyarthritis and spondylitis in BALBIc mice. We have examined the properties of 3 monoclonal antibodies (MAb) to human fetal cartilage PG isolated from immunized mice that cross-react with mouse cartilage PG. Compared with sera from arthritic mice, which contain antibodies reactive with keratan sulfate, MAb 202 (IgG1) reacted only with a protein-related epitope that is distributed on both hyaluronic acid-binding and chondroitin sulfateattachment regions. MAb 813 (IgGl) Proteoglycan (PG) and collagen, which are major structural components of the extracellular matrix of articular cartilage, have been implicated in autoimmune mechanisms leading to the development and/or persistence of inflammatory diseases in humans, such as rheumatoid arthritis, ankylosing spondylitis, and relapsing polychondritis (1-7). The injection of type I1 collagen from cartilage produces polyarthritis in genetically predisposed strains of rats (8,9) and mice (10). Similarly, expression of immunity to cartilage PG in rabbits (1 1,12) and dogs (1 1) accompanies the development of inflammatory arthritis.Cellular immunity to cartilage PG has been observed in patients with ankylosing spondylitis (7,13) and rheumatoid arthritis (6,7). Female BALB/c mice develop a peripheral and axial polyarthritis when immunized intraperitoneally with human fetal PG in Freund's complete adjuvant (14). Clinical studies including radiographic and scintigraphic analyses have shown joint hypercapitation, progressive erosions, de-

Immune response by host after allogeneic chondrocyte transplant to the cartilage

“…CARTILAGE MATRIX Numerous components of cartilage matrix, such as collagen type II, IX, and XI (Bujia et al, 1994a;Paroczai and Nemeth-Csoka, 1988;Takagi and Jasin, 1992), core protein of proteoglycans (Dayer et al, 1990;Glant et al, 1998;Goodstone et al, 1996), or link proteins (Doran et al, 1995) have antigenic properties and could be involved in transplant rejection. Thus, anti-type II collagen antibodies present in sera of patients with rheumatoid arthritis reacted with chondrocyte membrane antigens (Takagi and Jasin, 1992).…”

Proteoglycan‐induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice

“…This arthritis and spondylitis appear t o be strain specific (but not haplotype specific) and sex related (9). The development of this arthritis is associated with the natural presence of cellular immunity t o mouse PG ( (9), and some are capable of eliciting a loss of PG from articular cartilage in vivo (25). In the present study, we demonstrated that arthritis with spondylitis can be adoptively transferred t o healthy but irradiated mice by a combination of T and B lymphocytes from mice with arthritis.…”

Effect of pregnancy on proteoglycan-induced progressive polyarthritis in BALB/c mice: remission of disease activity

“…The PG-induced arthritis, described recently, shows many deliveries was approximately the same as the ratio of caesarian similarities to human RA [1][2][3]6,16], and this is the only sections (20%) due to joint alterations of the pelvis in juvenile inflammatory autoimmune animal model which has close to RA [19]. However, most of the pregnancies of arthritic mice 100% incidence in genetically susceptible BALB/c mice.…”

“…fetal or newborn human, fetal pig and chondrocytes [6] and able to deplete PGs in articular cartilage canine articular cartilage) PGs [1,2,5]. Remissions and exacer- [3], significantly reduces the onset time of passively transferred bations of local inflammatory processes alternate, leading to the arthritis [6]. Transfer of arthritis, however, never occurs after complete deterioration of articular cartilage and intervertebral injection of serum alone from arthritic animals [6] or after discs as well as to deformities and ankylosis of axial and injecting animals with autoreactive MoAbs to mouse cartilage peripheral joints within a 6-9 month period of the disease [1].…”

“…Spleen, liver, kidney, Assessment of disease activity lung, small intestine, hind paws and lumbosacral spine were The appendages of all mice (immunized arthritic and nonremoved, fixed, decalcified and embedded in paraffin. Multiple immunized non-arthritic) were examined three times a week to sections were stained with haematoxylin and eosin or with record clinical arthritic changes which were documented as toluidine blue at pH 1 5, 3 5 and 5*5 as described [3]. Non-parametric statistics were used, including Wilcoxon's°2 3 4 5 6 7 8 signed ranks test and Friedman's analysis of variance as Acute arthritis score described in our previous paper [13].…”