Rheumatoid Arthritis, Mycobacterial Antigens and Agalactosyl IgG

Rook, G.A.W.

doi:10.1111/j.1365-3083.1988.tb01480.x

Cited by 32 publications

(10 citation statements)

References 26 publications

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“…Mycobacterial infection is the most clearly established cause of a raised %Gal(O), and the isolation of extremely slow-growing mycobacterium-like organisms from human Crohn's disease material [27] has been discussed elsewhere in relation to rheumatoid arthritis [25]. These connections, while very speculative, agree well with what we know about raised %Gal(O) in man [29]. It is raised not only in rheumatoid arthritis, but also in Crohn's disease [28], in tuberculosis [2], and in leprosy during episodes of erythema nodosum leprosum (ENL) [16].…”

Section: The Possible Role Of Il6 In the Induction Of Agalactosyl Iggsupporting

confidence: 67%

The role of oil and agalactosyl IgG in the induction of arthritis in rodent models

Rook¹,

Thompson

Buckley

et al. 1991

Eur J Immunol

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The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 micrograms of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50-75 days, although levels at 150-200 days were not affected. The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p less than 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal(O) is raised, is more likely to evoke disease. Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.

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Section: The Possible Role Of Il6 In the Induction Of Agalactosyl Iggsupporting

confidence: 67%

The role of oil and agalactosyl IgG in the induction of arthritis in rodent models

Rook¹,

Thompson

Buckley

et al. 1991

Eur J Immunol

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“…Based on the strong sequence homologies in HSP families from pro-and eukaryotes (Jindal et al, 1989;Lamb et al, 1989) it seems possible that HSP, particularly the 65-kD HSP, are the common denominator of all the causes discussed in the past for RA (Holoshitz era/., 1986;Rook, 1988). In addition, the postulated antigenic mimicry as a basis for the induction of RA (van Eden, Holoshitz & Cohen, 1987;Gaston et al, 1989) would be more acceptable.…”

Section: Discussionmentioning

confidence: 99%

Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial heat-shock protein

Yang

Gasser

Feige

1990

Clinical and Experimental Immunology

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SUMMARYAdjuvant arthritis in Lewis rats is a model of T cell-mediated autoimmune arthritis resembling human rheumatoid arthritis, A nonapeptide from the 65-kD heat-shock protein of Mycobacterium bovis BCG, amino acid sequence 180-188, has been described to carry the dominant immunogenic epitope(s) for both arthritis-protective and arthritogenie T cell clones. Here we demonstrate that immunizations with the synthetic nonapeptide completely protected rats against adjuvant arthritis induced by M. tuberculosis. Interestingly, deletion of the N-teminal threonine of the nonapeptide resulted in loss ofthe protective activity, Pretreatments with the nonapeptide resulted in an immune response to the nonapeptide and to M. tuberculosis. After immunizations with the synthetic nonapeptide, only low titres of nonapeptide-specific antibodies were produced, whereas a significant cellular immune response to the nonapeptide was observed. In addition, the protection was transferable to naive rats by spleen T cells. These findings document the requirement of a T cellspecific immune response to the dominant epitope ofthe 65-kD mycobacterial heat-shock protein for the protection against adjuvant arthritis and suggest the feasibility of immune intervention in autoimmune arthritis through the use of synthetic peptides.

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“…Other parameters that are routinely used today to evaluate disease activity in AA include: measurement of acute phase proteins [6,10,12,13], measurement of histological changes of the joints by noninvasive methods such as x-ray analysis [14], and recently, by MRI [15,16]. Important reviews to read on this subject include those by Van Arman [17], Mohr and Wild [18], Billingham and Devies [19], Owen [20], Billingham [21], Lewis et al [22], Rook [23] and Billingham [24].…”

Section: Historical Backgroundmentioning

confidence: 99%