ORIGINAL ARTICLE Mycobacterium tuberculosis lipoarabinomannan antibodies are associated to rheumatoid arthritis in Sardinian patients G. L. Erre & D. Cossu & S. Masala & G. Mameli & M. L. Cadoni & S. Serdino & M. G. Longu & G. Passiu & L. A. Sechi Received: 14 February 2014 /Revised: 12 May 2014 /Accepted: 12 May 2014 /Published online: 25 May 2014 # Clinical Rheumatology 2014 Abstract Little is known regarding the environmental factors at play in igniting rheumatoid arthritis (RA) autoimmunity, although an association between Mycobacteria and RA has been documented. This pilot study focused on examining a possible involvement of Mycobacterium tuberculosis (MTB) and Mycobacterium avium ss. paratuberculosis (MAP) in RA. We measured out the serum levels of IgG antibody against different mycobacterial antigens in Sardinian patients and controls, by an enzyme-linked immunosorbent assay. The population study was composed of 61 RA patients under different therapies and 52 healthy controls, whereas the anti- gens tested were MTB lipoarabinomannan (ManLAM), MAP heath shock protein 70, and MAP protein tyrosine phospha- tase. The frequencies of anti-ManLAM antibodies were higher in the RA group (23 %) compared to the healthy controls (5.7 %) (AUC=0.7; p <0.0001), whereas serum re- activity to MAP antigens was not observed. ManLAM antigen was also detected in the plasma of three RA patients (which were anti-ManLAM antibody positive) by Western blot anal- ysis using anti-Man-LAM monoclonal antibodies. The data produced corroborate the hypothesis of a potential association between MTB ManLAM and RA disease, but so far, further studies are necessary to understand its role in RA pathogenesis. Keywords ELISA . Lipoarabinomannan . Mycobacteria . Rheumatoid arthritis Introduction Rheumatoid arthritis (RA) is a disease characterized by per- sistent synovial inflammation, joint destruction, and autoanti- bodies production. Only 50 % of the risk for RA is attributable to genetic factors; the remaining 50 % is due to environmental factors such as microbial infection, which may be associated with RA development [1]. In fact, nucleic acids and antigens from different bacterial species were found in RA joint samples [2]. Noteworthy, several studies highlighted the presence of Mycobacterium tuberculosis (MTB) antigens or mycobacterial components in RA synovial fluid [2, 3]. Complete Freund’ s adjuvant (CFA), which contains heat- killed mycobacteria, is commonly administrated in many ex- perimental animal models of autoimmune disease such as adjuvant-induced arthritis (AIA). Moreover, a number of my- cobacterial substances that can account for CFA immunoadjuvant effects have been identified [4]. For exam- ple, muramyl dipeptide or glycolipids as trehalose dimycolate or lipoarabinomannan (LAM) are all capable of replacing mycobacteria in CFA for immunity induction [4]. LAM has been recently reported to be a useful marker to detect Tuberculosis infection [5]. Moreover, LAM has been included in the panel of tests that need to be used in the point- of-care diagnosis [6, 7]. It was also ascertained that mycobacterial heat shock pro- tein 65 (HSP65) can play a role in AIA development mainly because it is able to induce the production of arthritogenic pro- inflammatory cytokines [8]. HSP family members are highly conserved in human and bacteria; therefore, cross recognition is likely to occur, leading to autoimmunity. This pilot study mainly focuses on studying the asso- ciation between Mycobacteria and RA in the context of a Sardinian population. On one hand, we wanted to get deeper in understanding the role played by MTB; on the G. L. Erre and D. Cossu contributed equally to the work G. L. Erre : S. Serdino : M. G. Longu : G. Passiu Dipartimento di Medicina Clinica e Sperimentale, Università di Sassari, Sassari, Italy D. Cossu : S. Masala : G. Mameli : M. L. Cadoni : L. A. Sechi (*) Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy e-mail: sechila@uniss.it Clin Rheumatol (2014) 33:1725–1729 DOI 10.1007/s10067-014-2678-z