Glycosylation of IgG during potentially arthritogenic lentiviral infections.
Agalactosyl IgG [Gal(0)] was first discovered in patients with rheumatoid arthritis (RA). However, the proportion of this glycoform is also raised in tuberculosis and leprosy. This has helped reinforce the suggestion that RA may be triggered by a mycobacterium-like slow bacterial infection. On the other hand, arthritis can occur in mycobacterial diseases, so raised Gal(0) could be associated with a tendency to arthritis, rather than with a particular type of infection. Therefore, we wished to find out whether the percentage of Gal(0) [%Gal(0)] is increased in sheep and goats following infection with maedi visna virus or caprine arthritis encephalitis virus (CAEV), both of which can lead to inflammatory synovitis. We found that the normal level of Gal(0) in these species is much lower than in humans. Goats infected with CAEV or Mycobacterium paratuberculosis (used as a control mycobacterial infection) had a significant increase in %Gal(0), though it was still below the level seen in normal humans. Studies by Western blot confirmed the presence of terminal N-acetylglucosamine on heavy chains, and percentages of Gal(0) comparable to those seen in human RA could be generated by exposing goat IgG to streptococcal beta-galactosidase. The rise in %Gal(0) was greatest in members of infected herds that were just starting to manifest arthritis, and tended to be lower in those in which severe carpitis had developed at the time of bleeding, implying the possibility that raise %Gal(0) may be an early or predisposing event for the development of arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
McCulloch
J
J
UCL Medical School, London, UK.
Zhang
Y W
YW
Dawson
M
M
Harkiss
G D
GD
Peterhans
E
E
Vogt
H R
HR
Lydyard
P M
PM
Rook
G A
GA
D000117:Acetylglucosamine / Q000032:analysis; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001168:Arthritis / Q000276:immunology*; D016088:Arthritis-Encephalitis Virus, Caprine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D006031:Glycosylation; D006041:Goats; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D016180:Lentivirus Infections / Q000276:immunology* / Q000473:pathology; D010283:Paratuberculosis / Q000276:immunology; D012756:Sheep; D014790:Visna-maedi virus
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; C064155:agalactosyl IGG; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins; D000117:Acetylglucosamine