Sunday, January 21, 2007

Common infection might set stage for lupus

Infection is known to trigger certain autoimmune diseases, e.g., rheumatic fever and ankylosing spondylitis. The initial immune response against the pathogen is thought to also recognize "self" proteins called autoantigens and may later spread to recognize additional autoantigens. These investigators wished to test their suspicion that Epstein Barr virus (EBV) triggers systemic lupus erythematosus (SLE). They previously showed that the first SLE autoantigen is the RNA-binding protein Ro. Here, they analyzed blood samples from a repository drawn from more than 5 million people. They found 29 people who later developed lupus and who had donated a blood sample before they developed Ro-specific autoantibodies. Nine of these early sera contained autoantibodies that recognized only a single small portion of Ro. All of these early, Ro-specific antibodies cross-reacted with a completely different small fragment of the EBV nuclear protein EBNA-1, suggesting that the crossreaction could be an early event in the disease. To test this, they immunized rabbits with peptides matching Ro or EBNA-1. Strikingly, both groups of rabbits developed lupus-like symptoms, including reduced numbers of white blood cells (leukopenia), clotting factors (thrombocytopenia) and kidney function. This paper connects a common infection with lupus. It remains to be determined why lupus develops in relatively few of the many EBV infected adults.
McClain et al. Nat.Med. 11, 85 - 89 (2004) "Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry"


Reuel said...

More EBV in SLE?
This free, full text paper by Moon et al. reports a striking elevation of EB viruses in SLE patients. Using semi-quantitative PCR, they find similar rates of infection (98.5% versus 94%). However, they find EBV is elevated 15-fold in SLE patients vs. healthy controls: "(mean ± standard deviation: 463 ± 570 EBV genome copies/3 ug PBMC DNA versus 30 ± 29 EBV genome copies/3 ug PBMC DNA; P = 0.001)"

Does anybody know of similar studies that confirm or refute their suggestion that that "EBV infection is abnormally regulated in SLE"?

Anonymous said...

RE: More EBV in SLE
This older paper, also full, free text, by Tosato et al. [], report increased EBV-infected B cells in rheumatoid arthritis patients but not SLE patients. They write "the mean frequency of spontaneously transforming B cells in RA patients was 10.1/10(6) B cells, which was significantly greater than that of the normal controls, 2.8/10(6) B cells (P less than 0.005). The group of patients with SLE did not differ from the normals (P greater than 0.4)."

Since B cells are the primary target of EBV, it seems unlikely that other (non-B) cells could account for the difference.

Anonymous said...

Age, EBV, and MS
Some people think the person's age upon EBV infection is important. This paper "describes cumulative circumstantial evidence which strongly points to a post-pubertal primary Epstein-Barr virus infection as this unidentified etiological event in the induction of MS disease". So get it while you're young or remain cloistered.