A selection of international research, mirroring and subsequent to the life’s work of Dr. Thomas McPherson Brown, correlating various mycoplasma species to the etiopathogenesis of rheumatoid arthritis (RA). Mycoplasmas are the smallest living organisms that are currently known to science. Described as closely resembling L-forms, they lack a cell wall, are parasitic in nature, and those having a proclivity for human tissues can invade and inhabit host cells to reside intracellularly, sequestering nutrients from the host for their existence. Science-based evidence has demonstrated that these organisms also produce superantigens (described by Dr. Brown as endotoxins) that excite the immune system to produce a cascading inflammatory response. While they may reside in acutely-infected tissues, such as the oral cavity, lungs, or genitals, they also demonstrate an ability to translocate via the circulatory system to inhabit distant sites, leading to multi-organ system involvement, as well as the joints and connective tissues. As microbes capable of initiating and perpetuating systemic inflammatory diseases, mycoplasmas are known to be particularly harmful to the immune-compromised patient, as well as those with certain genetic predispositions.
Simultaneous Detection of Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma arthritidis in Synovial Fluid of Patients with Rheumatoid Arthritis by Multiplex PCR. Arch Iran Med. 2015 Jun;18(6):345-50. doi: 015186/AIM.004
An Iranian study was conducted, using polymerase chain reaction testing (PCR), to analyze 131 synovial fluid (SF) samples taken from the joints of rheumatoid arthritis (RA) patients to determine the prevalence of mycoplasma. Mycoplasma was found in 53.4% of RA patients overall, with Mycoplasma pneumoniae being the most prevalent strain, found in 30 samples (22.9%). Mycoplasma hominis was found in 23 samples (17.5%) and Mycoplasma arthritidis in 13 samples (9.9%). The authors recommend multiplex PCR assays for RA patients to ensure appropriate anti-mycoplasma treatment.
Presence of Mycoplasma fermentans in the bloodstream of Mexican patients with rheumatoid arthritis and IgM and IgG antibodies against whole microorganism. BMC Musculoskelet Disord. 2009 Aug 3;10:97.
Mexican researchers studied 219 blood samples from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APL) and tested for various mycoplasma strains using polymerase reaction testing (PCR), ELISA and immunoblotting assays, and results were compared with healthy controls. Patients with APL and healthy controls were negative for mycoplasma and very small percentages of SLE patients were positive for M. fermentans, M. hominis, and M. urealyticum. RA patients, however, showed significant numbers infected with M. fermentans (20/87 positive by culture and direct PCR, 49/87 positive by ELISA IgM and 4887 by IgG, and 35/87 by immunoblotting for IgM and 34/87 for IgG) as compared to controls. The authors point to M. fermentans as a strong contender for an infectious arthritogenic agent in humans and specifically for RA.
Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis. Biochem Biophys Res Commun. 2008 May 2;369(2):561-6. doi: 10.1016/j.bbrc.2008.02.079. Epub 2008 Feb 26.
Japanese researchers report that glycolipid-antigens (GGPL-I and III) belonging to Mycoplasma fermentans, an infection suspected in rheumatoid arthritis (RA), are major causative pathogenic antigens and GGPL-III antigens were detected in 38.1% of RA patients’ tissues, but not in osteoarthritis or controls. This specific antigen was found to induce the production of inflammatory cytokines, TNF-alpha and IL-6, from mononuclear cells in peripheral blood samples, and also led to the proliferation of synovial fibroblasts in RA. Although further study is needed to determine if these findings indicate causality in RA, the authors suggest that new, safe and effective treatments directed at abrogating the effects of this antigen could provide a hopeful treatment.
Distribution of Mycoplasma pneumoniae and Mycoplasma salivarium in the synovial fluid of arthritis patients. J Clin Microbiol. 2007 Mar;45(3):953-7. Epub 2006 Nov 22.
British researchers at St. George’s University of London found Mycoplasma pneumoniae in 70% of the joints of rheumatoid arthritis (RA) patients, in 100% of non-rheumatoid inflammatory arthritis patients, and in 80% of osteoarthritis patients by very sensitive nested PCR testing, as compared to findings (50%) in biopsied synovial exudates of patients with traumatic knee injuries. This infection was also associated with increased synovial fluid in arthritis flares, but not found in the synovial fluids of trauma patients. The authors report sporadic findings of Mycoplasma salivarium and that Mycoplasma fermentans had been previously identified in RA joints, but not for osteoarthritic patients, and speculate that these microorganisms may contribute to chronic inflammation within the joints.
[Frequency of different infectious agents persistence in mononuclear leukocytes of blood and synovial fluid in patients with rheumatoid arthritis]. Lik Sprava. 2005 Jul-Sep;(5-6):28-32.
A Ukranian study of mononuclear leukocytes (ML) in the blood and joint synovial fluid of 218 rheumatoid arthritis (RA) patients, as compared with controls and using various testing methods was undertaken to determine the frequency with which various infectious organisms could be found. Results determined that RA patient ML’s were infected with greater frequency with Mycoplasma arthritidis, Mycoplasma fermentans, Chlamydia trachomatis, and several viruses.
Relationship between rheumatoid arthritis and Mycoplasma pneumoniae: a case-control study. Rheumatology (Oxford). 2005 Jul;44(7):912-4. Epub 2005 Apr 6.
Based upon animal models of arthritis caused by mycoplasma infections, a case-controlled study of 78 rheumatoid arthritis (RA) patients and 156 controls was undertaken to evaluate a hypothetical association between Mycoplasma pneumoniae and RA. After accounting for quantifiable participant variables, these authors conclude that M. pneumoniae could be a co-factor in RA pathogenesis and call for further study of this association.
Detection of Mycoplasmal Infections in Blood of Patients with Rheumatoid Arthritis. Rheum, 1999, 38:6, 504-509.
Blood leucocytes of rheumatoid arthritis (RA) patients (14 male and 14 female) in the United States were studied for the presence of four strains of mycoplasma (M. fermentans, M. hominis, M. pneumoniae and M. penetrans), using forensic polymerase chain reaction (PCR) testing. Results were consistent for males and females, with 8/28 positive for M. fermentans, 5/28 positive for M. pneumoniae, 6/28 for M. hominis, and 1/28 for M. penetrans. In 36% of the patients, more than one type of mycoplasma was found in the blood leucocytes and of those who were co-infected, all had M. fermentans in combination with another species.
Mycoplasma Infection and Rheumatoid Arthritis: Analysis of Their Relationship Using Immuno-blotting and an Ultrasensitivie Poly-merase Chain Reaction Detection Method. Arthritis Rheum. 1997 Jul;40(7):1219-28.
An American study was undertaken to determine if there was an association between rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and various mycoplasma species in blood sera and synovial fluid samples. Although persistence of mycoplasma DNA in the synovial fluid or tissue of patients with RA or JRA wasn’t detected, serologic evidence of previous mycoplasma exposure was common.
Systematic detection of mycoplasmas by culture and polymerase chain reaction (PCR) procedures in 209 synovial fluid samples. Br J Rheumatol. 1997 Mar;36(3):310-4.
French researchers studied 209 samples of synovial fluid using 3 different testing methods. Half the samples were drawn from those with inflammatory rheumatic diseases; rheumatoid arthritis (RA – 27 patients), spondyloarthopathy (SpA – 28 patients), connective tissue disease (CTD – 5 patients), and unclassified arthritis (UA – 45 patients). The remaining half of samples came from patients with other forms of arthritis. Of the 8 samples that tested positive for mycoplamas, all had an inflammatory rheumatic disease and the authors conclude that this raises the question of mycoplasma playing a role in the etiopathogenesis of rheumatic diseases, particularly RA.
Mycoplasma fermentans, but not M penetrans, Detected by PCR Assays in Synovium from Patients with Rheumatoid Arthritis and Other Rheumatic Diseases. J Clin Pathol. 1996 Oct; 49(10): 824–828.
In a large scale study conducted by British researchers, Mycoplasma fermentans was found in the joints of patients with inflammatory rheumatic diseases, including rheumatoid arthritis (RA), spondyloarthropy (SpA), psoriatic arthritis (PsA), and unclassified arthritis (UA). The authors remain uncertain as to whether M. fermentans is involved in the etiopathogenesis of these rheumatic diseases or just an incidental finding.
Mycoplasma fermentans in Joints of Patients with Rheumatoid Arthritis and Other Joint Disorders. Lancet, May 18, 1996; 347, 1418.
An abstract is not available for this study, but it may be available for purchase from, or with subscription to, the specified journal.
Mycoplasma pneumoniae and Mycoplasma genitalium in synovial Fluid Isolate, JG Tully, DL Rose, JB Baseman, SF Dallo, AL Lazzell, CP Davis, J Clin Microbiol, 1995; 33:7, 1851-1855.
Case study of a patient with pneumonia, who developed post-infectious polyarthritis, was found to test positive for two types of mycoplasma in synovial fluid – in initial testing, Mycoplasma pneumoniae was identified, and, in later re-testing, Mycoplasma genitalium was also identified. The authors speculate on evidence suggestive that these infections may be a cause of post-infectious autoimmunity and the need for improved laboratory techniques to accurately identify different species.
Mycoplasma genitalium in the Joints of Two Patients. Euro J Clin Rheum, 1994; 13, 1066-1069.
In a small-scale British study of synovial fluid drawn from 13 rheumatic patients, a 58-year old male with rheumatoid arthritis that had evolved from juvenile polyarthritis was found to have Mycoplasma genitalium in his knee. In a second patient, a 25-year-old male with Reiter’s Syndrome, synovial fluid was polymerase chain reaction (PCR)-positive for Mycoplasma genitalium in addition to a finding of reactive mononuclear cells to ureaplasmal antigens that was determined by proliferation assay.
Indication of Mycoplasmas in the Synovial Fluid of Rheumatoid Arthritis Patients. Zh Mikrobiol Epidemiol Immunobiol 1983; 9: 63-66.
A Russian study of rheumatoid arthritis (RA) synovial fluid specimens found that 30% were positive for mycoplasmas and their antigens using two testing methods. By further cell culture of mycoplasma specimens, these researchers were able to identify two species, M. arthritidis and M. fermentans.