Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported that rabbit anti-idiotypic antibody (Ab2) against mAb, termed 1-5 (Ab1) and reactive with human type II collagen (CII) induced antibody response to CII in DBA/1J mice susceptible to collagen-induced arthritis. In the present study, we further characterized the anti-CII antibody response elicited by Ab2 with respect to epitope specificity, putative genetic background, and IgG subclass. Most of anti-CII antibodies (polyclonal Ab3) derived from Ab2-immunized mice were of the IgG1 subclass. We purified polyclonal Ab3, using a CII-coupled immunoadsorbent column and we developed monoclonal Ab3 from Ab2-immunized mice. Both purified polyclonal Ab3 and two monoclonal Ab3s specifically reacted with a selected epitope on CII, recognized by Ab1. The anti-CII antibody response stimulated by Ab2 was observed in DBA/1J (H-2q, Igh-1c) and DBA/2 (H-2q, Igh-1c) mice, but not in the BALB/c (H-2d, Igh-1a) and C57BL/6 (H-2b, Igh-1b) strains, thereby suggesting that the anti-CII antibody response elicited by Ab2 is controlled by the Igh gene.
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PMID:Characterization of the antibody response against the type II collagen induced by anti-idiotypic antibody. 169 9

The T cell reactivity against type II collagen (CII) was analyzed in the collagen-induced arthritis-susceptible mouse strain DBA/1. It was shown that the proliferative response in lymph node cells from rat CII-immunized mice was mainly directed against a foreign determinant present on all heterologous CII tested but not on autologous CII. A T cell line with this reactivity reacted with high sensitivity with CII and the determinant was mapped to the CB11 fragment of CII. A weak autoreactive response could be detected in the primary cultures using high concentrations of mouse CII and this reactivity remained after several stimulations with high concentrations of rat CII but not with low concentrations of rat CII. A similar response against mouse CII but with only limited cross-reactivity to rat CII was seen when culturing the cells with mouse CII as antigen. The optimal concentration for the autoreactive response was always more than 100-fold higher than for the response of the T cells specific for heterologous CII. An anti-CII T cell response could also be detected in spleen cells from unimmunized mice and the strongest response was obtained using autologous CII. These results suggest that T cells recognizing self CII are normally activated in the DBA/1 mouse and possibly as a consequence exhibit a clonal anergy pattern with a weak proliferative response only at high concentrations of CII.
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PMID:Analysis of type II collagen-reactive T cells in the mouse. I. Different regulation of autoreactive vs. non-autoreactive anti-type II collagen T cells in the DBA/1 mouse. 169 31

Some mouse monoclonal antibodies raised against chicken type II collagen suppressed or delayed the onset of chicken type II collagen-induced arthritis in DBA/1 mice. This was correlated with the suppression of anti-mouse type II collagen antibody responses following immunization with chicken type II collagen. The epitopes recognized by the suppressive antibodies were found to be present on cyanogen bromide (CB)-digested collagen peptides CB-11 and CB-12. This was also confirmed by the finding that administration of the CB-11 or CB-12 peptide suppressed the induction of arthritis.
Arthritis Rheum 1991 Jan
PMID:Suppression of type II collagen-induced arthritis by monoclonal antibodies. 170 98

Immunization of certain strains of mice with native type II collagen (CII) induces both development of arthritis and an antibody response to autologous CII. The autoantibody response in a high-responder strain, the DBA/1 mouse, has been described earlier, and a number of monoclonal antibodies have been characterized for arthritogenicity and autoreactive binding to cartilage in vivo and in vitro. Here we map the antigenic epitope of one of these arthritogenic monoclonal antibodies (CII-C1). It belongs to a group of antibodies recognizing the CNBr fragment alpha 1(II)-CB11 of CII. Using the enzyme-linked immunosorbent assay technique, we show that the antibody reacts only with native, triplehelical CII, but not with other collagens. The antibody is able to stain specifically the CB11 fragment by immunoblotting, suggesting some partial renaturation of the CNBr fragment into triple-helical structures after blotting. The binding site of CII-C1 on CB11 was further focused by rotary shadowing of antibody-labeled CII to a site 89 +/- 8 nm from the amino end of CII, corresponding to the middle of CB11. This location was confirmed by cleavage of CB11 with trypsin, separation of the tryptic peptides by high-performance liquid chromatography and dot-blot analysis of the antigenic peptides with the CII-C1 antibody. Sequencing of the single positive peptide located the antigenic epitope within the sequence GFAGQAGPAGATGAPGRP (residues 316-333). Assuming 0.29 nm per residue, this corresponds to a position within 92-96.5 nm from NH2 terminal end of CII. Apart from glycine residues, which are not exposed on the triple-helical structure, only two amino acid residues (F-x-y-Q) are conserved in CII from different species but are not found in the triple-helix of other collagens except type IV collagen. Therefore, this structure is likely to be of critical importance for the binding of the CII-C1 antibody. Of potential importance is that this structure is also found in certain other arthritogenic proteins such as 65-kDa mycobacterial protein, in CMV and EBV.
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PMID:Identification of a major antigenic epitope on CNBr-fragment 11 of type II collagen recognized by murine autoreactive B cells. 170 64

The specificity of the recognition of type II collagen (CII) by T cells in the DBA/l mouse was analysed using fragments of chick and rat CII obtained by cyanogen bromide (CB) cleavage. Firstly, DBA/l mice were immunized with chick CB fragments 5, 8, 9, 10, 11 and 12. Ten days later the draining lymph node cells were cultured with rat and mouse CII and the proliferative response was determined by incorporation of [3H]thymidine. All peptides were capable of triggering T cells recognizing rat CII but only CB9 immunized mice responded well to mouse CII. Secondly, lymph node cells from DBA/l mice immunized with rat and mouse CII were cultured with the CB fragments, including rat CB10 and CB11, and the proliferative response was determined. After immunization with rat CII, the response was strongly dominated by T cells recognizing CB11 with equal responses against chick and rat CB11. After immunization with mouse CII only rat CB10 gave a strong response. It is concluded that several epitopes on the CII molecule can be recognized by T cells in the DBA/l mouse and that most of these epitopes are shared by rat and chick CII but not mouse CII. These epitopes exhibit strong immunodominance. In mice immunized with intact heterologous CII, the immunodominant response is directed against one or more epitopes on the CB11 fragment present on several heterologous CII but apparently not on mouse CII. In mice immunized with autologous CII the immunodominant response is directed against one or more epitopes on the CB10 fragment, present on rat and mouse CII. They are either absent in chick CII or located in the carboxyterminal end of the CB10 fragment where a cyanogen bromide cleavage site is present in chick CII but not in rat CII. These results suggest that the proposed importance of CB11 in collagen-induced arthritis is due to activation of T cells reactive with heterologous CII only. These cells may be important for the induction of the strong auto-antibody-response after immunization with heterologous CII. Structures of importance for direct T cell involvement in the arthritic process and recognized by autoreactive T cells are suggested to be found on CB10.
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PMID:Analysis of type II collagen reactive T cells in the mouse. II. Different localization of immunodominant T cell epitopes on heterologous and autologous type II collagen. 170 17

To determine whether native bovine type XI collagen (BXI) is arthritogenic, five strains of inbred mice were immunized with BXI/CFA. Arthritis was not observed in any of these strains, though it was prevalent in DBA/1 and B10.RIII controls immunized with bovine type II collagen (BII). Antisera from BXI-immunized mice reacted with mouse type XI collagen (MsXI), weakly with the alpha-chains of BXI, and minimally with mouse type II collagen (MsII). However, antisera to BII reacted with MsII and MsXI, indicating antibodies to conformation-independent epitopes shared by alpha 1(II) and alpha 3(XI). Mice immunized with BXI containing a small amount of BII developed arthritis much like those immunized with BII; sera from these mice reacted with MsXI and MsII. Delayed-type hypersensitivity responses differed from IgG responses, i.e., BXI elicited responses to alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II); BII, to alpha 3(XI) and alpha 1(II) exclusively. To determine whether alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II) are arthritogenic, DBA/1J mice were immunized with each alpha-chain. Arthritis was seen in mice injected with alpha 3(XI) or alpha 1(II). Sera to both alpha-chains reacted similarly with MsII and peptide fragment alpha 1(II)-CB11. Epitope mapping using polyclonal and mAb to type II collagen revealed that all polyclonal and 11 of 14 mAb reacted with alpha 3(XI) and alpha 1(II), whereas three mAb reacted only with alpha 1(II). In conclusion, BXI is immunogenic but not arthritogenic in five strains of mice, whereas alpha 3(XI) and alpha 1(II) are arthritogenic and immunogenic in DBA/1 mice and share greater than or equal to 11 epitopes recognized by autoantibody.
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PMID:Immunity to type XI collagen in mice. Evidence that the alpha 3(XI) chain of type XI collagen and the alpha 1(II) chain of type II collagen share arthritogenic determinants and induce arthritis in DBA/1 mice. 171 Feb 40

Monoclonal mouse antibodies specific for the major epitopes on mouse type II collagen (CII) were biotinylated and injected into neonatal and adult mice. Anti-CII antibodies, specific for four different epitopes on the CII molecule, could be shown to bind specifically to joint surfaces in the paws of 2-day-old syngeneic DBA/1 mice after an intraperitoneal injection of 100 micrograms of biotinylated antibody. The anti-CII antibodies did not bind to cartilage from DBA/1 mice in vitro, unless the sections were pretreated with hyaluronidase or the specimens decalcified prior to freezing, showing that the epitopes are accessible in vivo but not in vitro. By analyzing the in vivo binding capacity for a number of monoclonal anti-CII antibodies which represented different IgG subclasses, it could be demonstrated that binding to the same epitopes occurred independent of IgG subclass. However, one epitope (denoted "B1") was only weakly detected, possibly due to the fact that the antibody used (CIIB1) crossreacts with type I collagen and C1q. Monoclonal anti-CII antibodies, injected into neonates or adult mice, bound specifically to most, but not all, tissues containing CII; including hyaline joint cartilage, fibrous sternal and costal cartilage, tracheal cartilage and fibrous cartilage in the spine but not to CII-containing structures in the eye. The finding that CII, while present in cartilage, is accessible for antibody binding in vivo may have important implications for the availability of CII for the immune system and for the understanding of the development of pathological autoimmunity leading to collagen-induced arthritis in mice.
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PMID:Multiple epitopes on cartilage type II collagen are accessible for antibody binding in vivo. 172 Jun 77

The development of type II collagen-induced arthritis (CIA) in DBA/1 mice is readily accelerated by treatments with interleukin-1 beta (IL-1 beta). In an attempt to further characterize this IL-1 beta-mediated enhancement of CIA, we first examined the effects of IL-1 beta treatments in other "CIA-susceptible" strains and "CIA-resistant" mice. It was observed that treatments with IL-1 beta also enhanced the onset of arthritis in two B10 recombinant CIA-susceptible strains, B10.T (6R) and B10.DA, and in the SJL mice which develop CIA with a relatively low and variable incidence. On the other hand, IL-1 beta failed to augment the expression of arthritic disease in several CIA-resistant strains. We also investigated the potentiating effects of IL-1 beta in mice that were depleted of L3T4+ T cells. It was found that the ability of IL-1 beta to accelerate the development of CIA was significantly reduced in DBA/1 mice pretreated with the monoclonal anti-L3T4 antibody. In further studies, we demonstrated that the induction of CIA upon transfer with collagen-primed spleen cells was also augmented by IL-1 beta, and this enhancing effect by IL-1 beta on the adoptive transfer of CIA was associated with a significant increase in the levels of serum anti-collagen antibodies. Moreover, IL-1 beta treatments did not potentiate the induction of CIA in mice that were transferred with either collagen-immune splenic cells that were depleted of L3T4+ T cells or only T cells obtained from collagen-immunized animals. However, IL-1 beta enhanced the development of arthritis in animals that had been transferred with two subpopulations of collagen-immune cells: (i) enriched T cells and (ii) splenic cells that were depleted of L3T4+ T cells. Thus, IL-1 beta potentiated the inflammatory responses in animals that were genetically predisposed to developing arthritis. In contrast, IL-1 beta was incapable of accelerating the development of arthritis in various mouse strains that were genetically resistant to CIA. The administration of IL-1 beta also failed to potentiate the development of CIA in L3T4-deficient mice or in animals transferred with collagen-primed spleen cells that were depleted of L3T4+ T cells. These results indicate that IL-1 beta readily accelerates the induction of arthritis when the disease is present, but that IL-1 beta is incapable of promoting the expression of the arthritis in the absence of underlying disease.
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PMID:Interleukin-1 enhances the development of type II collagen-induced arthritis only in susceptible and not in resistant mice. 172 80

The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
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PMID:Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. 175 95

It was found that the percentage of IgG-associated agalactosyl N-linked oligosaccharides (G0) falls during normal human pregnancy and rises to values higher than before conception following delivery (n = 10, 39-55 days after delivery). Serial bleeds from a normal pregnant woman showed a fall in the percentage G0 during gestation and a rapid rise post-partum. A similar study on a pregnant arthritic woman with a pathologically elevated percentage G0 also showed a fall in percentage G0 during pregnancy and a rapid rise post-partum. The changes in IgG glycosylation in the pregnant arthritic woman occurred simultaneously with the pregnancy-induced remission and post-partum recurrence of disease. A further seven pregnant women with rheumatoid arthritis were studied and analysis of their G0 values pre- and post-partum confirmed the result. In a further series of experiments using an animal model of rheumatoid arthritis, DBA/1 mice with collagen-induced arthritis were found to have elevated G0 levels compared with control mice. The percentage G0 was found to fall simultaneously with pregnancy-induced remission to the same value as non-arthritic pregnant mice. Post-partum recurrence of arthritis in these mice was also accompanied by a simultaneous and rapid rise in percentage G0. Pseudopregnancy did not result in a change in the percentage G0, confirming the effect of true pregnancy. Since the proportion of agalactosyl IgG is abnormally high in the serum of patients with rheumatoid arthritis these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying remission of arthritis in humans during pregnancy.
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PMID:Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy. 179 27


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