Presence Of Infection By Mycobacterium Avium Subsp. Paratuberculosis In The Blood Of Patients With Crohn’s Disease And Control Subjects Shown By Multiple Laboratory Culture And Antibody Methods

Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohns disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to assess the degree of viable culturable MAP bacteremia in humans, definite identification of the organisms cultured and to assess if CD patients have a significantly higher rate of MAP infection compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients, two patients with CD and concurrent ulcerative colitis (UC), 14 patients with UC only and 140 non-CD controls. Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed no association between any of the groups tested. Nine subjects with positive Phage assay (8/9) or MAP culture (1/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.

The evidence for Mycobacterium avium subspecies paratuberculosis (MAP) as a cause of nonsolar uveal melanoma: a narrative review

“…The proposed association implies that evidence of MAP infection may be present in human UvM lesions and patients. Researchers have developed methods of detecting MAP in human tissue (140), blood (141), and feces (142,143). These identification methods can be applied to human UvM patients.…”

“…However, it is important to note again that sun exposure, in contrast to CM, is an unproven risk factor for UvMs presenting in the posterior region of the eye (9,167). Chemical fertilizers, ammonium nitrate, and various military exposures are other plausible agents that may underlie risk and should be considered when interpreting findings (140)(141)(142). The reader is reminded that association does not prove causation.…”

Advances in Understanding of the Immune Response to Mycobacterial Pathogens and Vaccines through Use of Cattle and Mycobacterium avium subsp. paratuberculosis as a Prototypic Mycobacterial Pathogen

“…Extensive studies have been reported since the publication of these findings that show Map is the causative agent of CD. See references [ 28 , 29 , 30 ] for more detailed information.…”

Cytokine expression in subjects with Mycobacterium avium ssp. paratuberculosis positive blood cultures and a meta-analysis of cytokine expression in Crohn’s disease

“…Recently, a multi-laboratory study employing blind testing of whole blood samples by multiple culture techniques, found widespread viable MAP bacteremia in the 61 CD patients and 140 non-CD control subjects. Nine subjects with a positive Phage assay (4/9) or MAP culture (5/9) were again positive with the Phage assay one year later (Kuenstner et al, 2020). Of the serological methods, the Hsp65 antibody method was best for identifying CD patients from non-CD controls (Kuenstner et al, 2020).…”