Mycobacterial DNA in recurrent sarcoidosis in the transplanted lung - a PCR-based study on four cases

Abstract

Sarcoidosis is a systemic granulomatous inflammation, which may be caused by mycobacteria other than M. tuberculosis complex (MOTT) in one-third of cases. A few cases of recurrent sarcoidosis in the transplanted lung have been reported. However, mycobacteria have been excluded by acid-fast stains only. We investigated four cases of recurrent sarcoidosis in lung transplant patients. Using PCR for the insertion sequence 6110 of Mycobacterium tuberculosis complex and a second PCR for the mycobacterial chaperonin (65-kDa antigen coding sequence), we looked for mycobacterial DNA. In three cases sequence analysis was also performed. One patient was negative for mycobacterial DNA in explanted, but positive for M. tuberculosis DNA in transplanted lung, qualifying this case as M. tuberculosis infection in the transplant. Three patients were negative for M. tuberculosis DNA, but were positive for MOTT-DNA in both explanted and transplanted lungs. In these three patients sequence identity of the amplified sequences before and after transplantation was proven, which rules out mycobacteriosis. Recurrent sarcoidosis does occur, but can only be proven by the exclusion of mycobacterial DNA. In cases of recurrent MOTT-DNA-positive sarcoidosis the diagnosis cannot be confirmed except by proof of sequence identity. Probably MOTT-DNA-positive sarcoidosis is more likely to recur in a transplanted lung.

Molecular Analysis of Sarcoidosis Tissues forMycobacteriumSpecies DNA

“…However, correlating the sensitivity of DNA extracted from bacterial culture to DNA extracted from formalin-fixed, paraffin-embedded tissue is not possible. Other laboratories that reported an assay sensitivity of 1–2 genome copies for IS6110 in sarcoidosis tissue extract were also unable to detect any IS6110 (11,27–29), which was consistent with our results. Studies assessing for IS6110 reflect a substantial portion of the literature that does not support the presence of mycobacterial DNA in the sarcoidosis tissue specimens (11,27,28,30).…”

Granulomatous Pneumonia, Lymphadenopathy, and Hepatopathy in an Adult Horse with Repeated Injection of BCG

“…The findings in the present patient are essentially the same as those described in 7 horses and termed idiopathic granulomatous pneumonia 18 . Those authors point out that the pulmonary lesions seen in their equine patients are very similar to those described in human sarcoidosis, and in recent studies of human sarcoidosis mycobacterial DNA has indeed been detected in lung tissue and blood 19,20–22 . This provides some evidence to suggest that mycobacteria may play a role in equine granulomatous (lung) disease.…”

The potential of the immunological markers of sarcoidosis in exhaled breath and peripheral blood as future diagnostic and monitoring techniques

“…If the remaining parenchymal cells cannot re-establish the normal architecture, T H 2 type cytokines (e.g. IL-4, IL-5, IL-10, IL-13) and macrophage-derived factors including fibronectin, platelet-derived growth factor, insulin-like Immunological markers of sarcoidosis 57 (Saboor et al 1992;Grosser et al 1999;Li et al 1999;Klemen et al 2000;Drake et al 2002;Eishi et al 2002;Gazouli et al 2002;Gupta et al 2007), which could suggest cell-wall deficient mycobacterial infection (Kon and du Bois 1997;Brown et al 2003), however, others have not found PCR evidence of mycobacterial DNA or RNA (Lisby et al 1993;Cannone et al 1997;Vokurka et al 1997) Elevated circulating IgG directed against mycobacterial catalase-peroxidase (KatG) peptides in sarcoidosis patients and other circulating antibodies against mycobacterial antigens (Song et al 2005), and other evidence of BAL and peripheral blood mononuclear cell responses to Mycobacterium tuberculosis heat shock proteins, mycolyl transferase antigen 85A, superoxide dismutase A, ESAT-6 and KatG peptides Drake et al 2007;Dubaniewicz et al 2007;Hajizadeh et al 2007;Allen et al 2008;Oswald-Richter et al 2009;Dubaniewicz 2010). A large worldwide study confirmed T H 1 responses to Mycobacterium tuberculosis KatG despite differences in patient phenotype, genetic and prognostic characteristics and showed that mKatG reactive CD4?…”