Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via Crossreactivity or Molecular Mimicry

Table 1

Characteristics of bacterial immune responses in patients with rheumatoid arthritis and ankylosing spondylitis (see [33, 34, 41, 42]).

	Rheumatoid arthritis (RA)	Ankylosing spondylitis (AS)
Disease-triggering bacteria	Proteus mirabilis	Klebsiella pneumoniae
Bacterial antigens	Hemolysin; Urease	Nitrogenase; Pullulanase
Self-antigens*	HLA-DR4/1; collagen XI	HLA-B27; collagens I, III and IV
Antibody isotypes	IgG	IgA and IgG
Source of bacterial infections	Upper urinary tract	Large bowel
Bacterial isolations	P. mirabilis isolated more significantly from urine of active RA patients	K. pneumonia microbes are more abundant in the large bowel of active AS patients
Evidence for cytotoxic activities	Proteus antibodies are cytotoxic to cells coated with crossreactive self antigens	Klebsiella antibodies are cytotoxic to cells coated with crossreactive self antigens
Countries**	England; Ireland; Scotland; USA; Canada; France; Norway; Bermuda; Japan; Taiwan; India; Netherlands; Spain; Russia and Finland	England; Scotland; USA; Canada; Slovakia; China; Netherlands; Turkey; Japan; Finland; Sweden; Mexico; Germany; Taiwan; India; Russia; Spain
Microbial controls^Δ	Klebsiella, Escherichia, Yersinia, Salmonella, Chlamydia, Shigella, Pseudomonas, Campylobacters, and viruses	Proteus, Escherichia, Yersinia, Salmonella, Streptococci, Borrelia, Pseudomonas, Candida, and Campylobacters
Disease controls^ΔΔ	AS, systemic lupus erythematosus, sarcoidosis, acute anterior uveitis, spondyloarthropathy	RA, psoriatic arthritis, osteoarthritis, reactive arthritis, systemic lupus erythematosus

* Self-antigens crossreactive with the corresponding bacterial antigens
**Countries with recruited cohort patients showing elevated levels of antibodies against Proteus (in RA), Klebsiella (in AS) as well as against the corresponding crossreactive self-antigens
^ΔMicrobial agents used as controls but showing no enhanced humoral immune responses in patients with RA or AS
^ΔΔDisease controls showing normal immune responses to Proteus (in RA) and Klebsiella (in AS).