title: Supplemental treatment of rheumatoid arthritis with natural milk antibodies against enteromicrobes and their toxins: results of an open-labelled pilot study.
abstract: BACKGROUND
  Environmental factors, particularly commensal bacteria in the gastrointestinal tract, may be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to evaluate whether natural milk antibodies against a wide spectrum of pathogenic enteromicobes and their toxins modify the disease activity in RA.
  
  
  METHODS
  Twenty patients with RA, whose disease activity was uncontrolled by authentic medications due to drug resistance, complications and/or risk factors were treated for 3 months with an oral administration of a whey protein concentrate (WPC) containing high levels of natural milk antibodies. Eighteen background-matched RA patients, not supplemented with milk antibody adjunct, were used as controls.
  
  
  RESULTS
  Statistically significant reduction of arthritis symptoms and improvement of intestinal disorders were observed only in the test group: effective in 8 (44%), possibly effective in 2 (12%) and not effective in 8 (44%) of 18 patients treated (2 patients withdrew) based on an ad hoc "evaluation point", the sum of variables that are improved more than 20% among the 8 core variables used for the American College of Rheumatology (ACR) response criteria. This disease modifying effect of the WPC disappeared upon cessation of treatment, but was reappeared upon reintroduction of it. Importantly, 7 of 8 non-responders carry DR15 haplotype (DRB1-1501 and 1502), whereas only 1 of 7 responders was DR15 positive (risk ratio: 6.1). Furthermore, the pre-clinical serum anti-LPS and anti-type II collagen antibody levels in the responders were higher or tended to be higher than those in the non-responders, suggesting that there are 2 sub-types of RA based on an interaction between gastrointestinal pathogens and MHC class II haplotypes.
  
  
  CONCLUSIONS
  The natural milk antibody preparation containing high levels antibodies against pathogenic enteromicrobes and their toxins seems to be effective in a certain RA subset, and deserves more attention as a potential adjunct in the treatment of RA.
  
  
  BACKGROUND
  UMIN000003128.
authors.affiliation: Katayama Orthopedic Rheumatology Clinic, Toyooka 13-4-5-17, Asahikawa, Japan. kou@kata-rheum.or.jp
authors.forename: Kou
authors.initials: K
authors.lastname: Katayama
authors.forename: Takeo
authors.initials: T
authors.lastname: Matsuno
authors.forename: Takaki
authors.initials: T
authors.lastname: Waritani
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Terato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shionoya
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D004755:Enterobacteriaceae / Q000254:growth & development / Q000472:pathogenicity*; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins / Q000008:administration & dosage*; D010865:Pilot Projects
chemical_list: D000906:Antibodies; D001427:Bacterial Toxins; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D008894:Milk Proteins