to Klebsiella, Proteus, and HLA-B27 Peptides in Japanese Patients
with Ankylosing Spondylitis and Rheumatoid Arthritis
YOSHITAKATANI, HARMALE TIWANA, SINSUKE HUKUDA, JUNICHI NISHIOKA, MARK FIELDER, CLYDE WILSON, SUKHVINDER BANSAL, and ALAN EBRINGER
Objective. To determine whether patients with ankylosing Spondylitis (AS) and patients with rheumatoid arthritis (RA) from Japan have antibodies to Klebsiella pneumoniae and Proteus mirabilis and to assess whether such antibodies are activated against peptides sharing sequences with HLA-B27.
samples from 152 Japanese patients, 52 with AS, 50 with RA, and 50 healthy
controls, were tested against 3 bacteria (K. pneumoniae, P. mirabilis,
and Escherichia coll) and 3 synthetic peptides (HLA-B27, pullulanase-D,
and scrambled pullulanase-D control peptide) by ELISA under coded conditions.
Samples were tested for elevations in IgG, IgA, and IgM antibody classes
in patients with active AS or RA, in patients with RA with probable disease,
and in patients with inactive AS. Disease activity was determined by an
elevated serum C-reactive protein (> 10 mg/1) level and elevated erythrocyte
sedimentation rate (> 20 mm/h).
Key Indexing Terms: ANKYLOSING
Ankylosing Spondylitis (AS) and rheumatoid arthritis (RA) are HLA linked inflammatory disorders. Over 90% of patients with AS possess HLA-B27 and a similar percentage of patients with RA possess HLA-DR1 or DR4'-3. In Japan, the frequency of HLA-B27 is only 0.41% in the general population4, and the prevalence of AS is reported to be 0.03-0.04%5-6. In contrast, the frequency of HLA-DR4 (mainly DW15 in Japanese) is about 40%, but the prevalence of RA is 0.3-0.5% in Japanese6-7, lower than the
From Department of Orthopaedic Surgery, Shiga University of Medical Science, Otxu. Japan; Life Science Centre. King i College. London, UK. K Tani, MO; S. Hukuda. MO: J. Nishioka, MD. Shiga University of Medical Science: H. Ttwana. PhD; M. Fielder. PhD; C. Wilson. PhD; S. Bansal, PhD; A. Ebringer. MD. King's College. Address reprint requests to Dr Y. Tani, Department of Orthopaedic Surgery. Shiga University of Medical Science. Tsukinowa-cho, Seta. Otsu. Shiga 520-21, Japan.
Caucasian rate8-9. These data suggest that the pathogenesis of AS and RA are mediated by factors, such as the immuno-genetic status of the patient and the involvement of environmental agents, similar to those observed in other countries.
An increase in anti-Klebsiella antibodies in patients with AS during the active phase has been reported in different geographical locations10'". Moreover, crossreactivity between Klebsiella and HLA-B27 has been reported by several groups12"14. In addition to the relationship between AS and Klebsiella, elevated levels of antibodies to Proteus have been identified in patients with active RA in Europe and America15'18. An amino acid homology between an outer membrane hemolysin protein of P. mirabilis and the susceptibility sequence in HLA-DRI and DR4 subtypes (DW14, DW15) has been reported19.
These reports suggest the possibility of bacteria being the causative agents of AS and RA. To explore these possibilities, we measured IgG, IgA, and IgM class specific antibodies to K. pneumoniae, P. mirabilis, and synthetic peptides containing HLA-B27 sequences by ELISA in Japanese patients with AS and RA.