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.

Multiplex PCR for the Detection of Mycoplasma fermentans, M. hominis, and M. penetrans in Patients with Chronic Fatigue Syndrome, Fibromyalgia, Rheumatoid Arthritis, and Gulf War Syndrome. Journal of Chronic Fatigue Syndrome 5(3-4):187-197 · December 2011.

Patients with chronic fatigue syndrome (CFS), fibromyalgia (FMS), rheumatoid arthritis (RA), and Gulf War Syndrome (GWS) were assessed by multiplex polymerase chain reaction (PCR) testing for various strains of mycoplasma (M. fermentans, M. hominis, and M. penetrans) and results were age- and sex-matched with healthy control samples. Results revealed that all 3 pathogenic mycoplasma strains were more prevalent in the patient groups than in the healthy control subjects and the authors state that multiplex PCR testing has a high degree of sensitivity, provides rapid results, and is cost-effective.

Mycoplasmal lipid-associated membrane proteins and Mycoplasma arthritidis mitogen recognition by serum antibodies from patients with rheumatoid arthritis. Rheumatol Int. 2011 Jul;31(7):951-7. doi: 10.1007/s00296-010-1612-1. Epub 2010 Oct 30.

Brazilian researchers studied Mycoplasma fermentans (M. fermentans) and Mycoplasma hominis (M. hominis) cellular products found in the blood serum of female patients by Western Blot testing that they hypothesize can be involved in the etiopathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Most notable was the frequent finding for mycoplasmal lipid-associated membrane proteins (LAMPs) by IgG antibodies (past infection) for both M. fermentans and M. hominis in RA patients, but there were no similar findings in the SLE or control blood samples. The authors state that because mycoplasma can be potent stimulators of the immune system and demonstrate strong reactivity in RA patients, that LAMPs could be researched as a type of mycoplasmal antigen that can induce and amplify human autoimmunity.

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.

Triggering and Exacerbation of Autoimmune Arthritis by the Mycoplasma arthritidis Superantigen MAM. Arth & Rheum, 1993; 36:7, 994-1002.

University of Utah School of Medicine researchers were able to demonstrate in the mouse model that a mycoplasma superantigen, called Mycoplasma arthritidis superantigen MAM, is able to trigger and exacerbate autoimmune arthritis by immunizing mice with porcine type II collagen. The authors speculate on the similarities of their findings with rheumatoid arthritis (RA) and that superantigens, like MAM, may play a role in this disease.

Peculiar Properties of Mycoplasmas: the Smallest Self-Replicating Prokaryotes. FEMS Micro Letters 100, 1992, 423-432.

In this review of the properties of mycoplasmas, the simplest and smallest of prokaryotic organisms possessing pathogenic capability to invade the human host, the author describes this cell-wall-deficient organism as a parasite, living within human host cells to feed off nutrients it cannot secure for itself. Infection with this organism is known to follow a chronic course due to its ability to hide within host cells and provoke immune reactions that result in symptomology. This author also points to contemporary research findings that speculate on an association of mycoplasmas with rheumatoid arthritis (RA) and AIDs.

Immunoglobulin M rheumatoid factor in patients with mycoplasmal pneumonia. Am Rev Respir Dis. 1986 Dec;134(6):1237-40.

In a study of blood sera from 20 patients with confirmed Mycoplasma pneumoniae and 4 patients with this infection, but without active pneumonia, researchers sought to discern if there was any relationship between IgM rheumatoid factor (IgM-RF) and IgG immune complex (IgG-IC) and the clinical aspects of this infection. The authors concluded that significant elevations of IgM-RF in the convalescent period might play a role in the recovery from this pneumonia, because active infection and exacerbations in disease activity were associated with lower levels in both IgM-RF and IgG-IC.

Detection of Mycoplasma arthritidis and Mycoplasma fermentans Antibodies in Rheumatoid Arthritis Patients by An Immunoenzyme Method.  Zh Mikrobiol Epidemiol Immunobiuol, 1985, 6:48-52

Russian researchers, using a specially-modified immunoenzyme assay, were able to detect antibodies for Mycoplasma arthritidis (in 6.5% of cases) and Mycoplasma fermentans (in 41.9% of cases), the former co-existing with the latter, in the blood sera of rheumatoid arthritis (RA) patients. While M. arthritidis antibodies generally show up in testing as present infection (IgM), antibodies to M. fermentans can show up as past infection (IgG) only, or both present and past infection simultaneously.

Immunologic responses in patients with Mycoplasma pneumoniae infections. Am Rev Respir Dis. 1983 Feb;127(2):175-9.

Using the enzyme-linked immunosobent assay testing method, research was conducted to measure patient serum concentrations for present (IgM) and past (IgG) Mycoplasma pneumoniae infections. Further testing of positive samples revealed the presence of rheumatoid factor (RF) with “remarkably high frequency” and that the development and persistence of RF during the clinical course of this form of pneumonia was also examined.

Arthritis Caused by Mycoplasma salivarium in Hypogammaglobulinaemia. Br J Rheum, Mar 5, 1983; 286, 762-763.

In Short Report, published in the British Journal of Rheumatology, the case of a 39-year-old woman, presenting with early-onset hypogammaglobulinemia, along with a history of symmetrical polyarthritis, and bronchiectasis, diagnosed at age 31, and treated with gammaglobulin, after which her arthritis resolved by 6 weeks. However, at age 37, the patient experienced intermittent diarrhea with low grade fever and a painfully inflamed, swollen knee. Mycoplasma salivarium was detected in synovial fluid, Mycoplasma hominis and Ureplasma urealyticum were cultured from oral and vaginal swabs, and Campylobacter organisms found in stool. In spite of IV and oral erythromycin treatment which resolved the diarrhea and other symptoms, knee swelling persisted. A further synovial fluid analysis still proved positive for M. salivarium and, in spite of further oral erythromycin treatment for 2 months and synovectomy, knee pain persisted. When minocycline therapy was initiated, the arthritis resolved swiftly. These authors stress the importance of evaluating immune-compromised patients for mycoplasma infections, which may require specialized lab testing and prolonged culturing and speculate that this organism gained access to the joint via blood circulation translocation from the mouth. While antibiotic sensitivity testing is helpful to determine appropriate therapy, these authors also recommend early treatment with IV tetracycline therapy as a first course of action, and continuing long-term if necessary.

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.

Comparative Characteristics of Joint Changes in Rats Infected with Mycoplasma fermentans and Mycoplasma arthritidis, AV Zil’fian, IuV Vul’fovich, IV Zherzheeva, GIa Kagan, Zh Mikrobiol Epidemiol Immunobiol 1981; 3: 42-45.

By inoculating rats with two species of mycoplasma, M. fermentans and M. arthritidis, Russian researchers were able to induce morphologically-varying forms of polyarthritis. While M. arthritidis produced an acute, purulent arthritis, M. fermentans resulted in polyarthritis that followed a sub-acute course that led to early joint damage. They also found that rat plasma cells produced a factor similar to human rheumatoid factor (RF) in synovial membranes.

Mycoplasma Infections as Models of Chronic Joint Inflammation. Arth & Rheum, 1979; 22:12, 1375-1381.

An abstract is not available for this study, but it may be available for purchase from, or with subscription to, the specified journal.




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