Isolation of M. leprae and M. lepromatosis protein antigens and the impact on global leprosy


By guest bloggers William Levis and Frank Martiniuk of NYU School of Medicine, Departments of Medicine and Dermatology

 

In the 1980’s, we made significant advances in the serodiagnosis of leprosy using carbohydrate antigens (Levis et al, 1986).  Since then, with the rapid advances on isolation and advances in protein technology, an international consortium of Dutch (Geluk et al, 2011), Brazilian and US scientists led by Duthie (Rada et al, 2011) and Spencer (Spencer et al, 2012) have added to this early work, making leprosy the most exciting immunologic disease for the study of antibodies and T-cell subsets including the old TH1-TH2 paradigm (Modlin, 1994) and the newer subsets of TH17, TH9 and TH22 now under intense study in human inflammatory and neoplastic skin diseases (Martiniuk et al, 2012; Lowes et al, 2013).

The recent Duthie and Spencer serologic test for leprosyis a major advance in leprosy diagnosis and management, as it can monitor therapy and detect subclinical cases that allow for early detection and treatment,  resulting in reduction of residual deformity.  The current difficult and technically challenging Fite histochemical method cannot detect subclinical cases.  Unpublished data also indicate the Duthie/Spencer test can detect but not distinguish what appears to be an emerging microbe, M. lepromatosis (Lowes et al, 2013; personal communication (John Spencer)).  The newly discovered mycobacterial species, M. lepromatosis, originally identified in Mexico, has also been reported in two Chinese immigrants from Asia (where two-thirds of all global leprosy exists ) with Lucio’s (Levis et al, 2012).

Lucio's has been described as far back as 1948, and until recently, most, but not all, cases have traditionally been from Mexico.  With a phenomenon as uncommon as Lucio's it is difficult to perform accurate global surveillance.  However,  it may be an emerging virulent mutant of the original M. leprae --- or is this only a recently discovered species (or strain) that escaped detection until Han and associates identified the first cases at M. D. Anderson Cancer Center in Houston, Texas? (Han et al, 2009).

Further investigation of these peculiar cases is required before it can be concluded that M. lepromatosis is a more virulent emerging species of M. leprae; this should include sequencing the whole genome.   Duthie, Spencer and the Dutch/Brazilian investigators including Orangelife, Inc. are continuing to work on combination of carbohydrate and protein antigens for diagnosis, contact survelliance, vaccine development, and distinguishing M. leprae and M. lepromatosis.

 

REFERENCES

 

Geluk A, Duthie MS, Spencer JS. (2011) Postgenomic Mycobacterium leprae antigens for cellular and serological diagnosis of M. leprae exposure, infection and leprosy disease. Lepr Rev 82:402-21

 

Han XY Sizer KC, Tan H-H. (2012) Identification of the leprosy agent Mycobacterium lepromatosis in Singapore. J Drugs Dermatol 11:168-172.

 

Han XY, Sizer KC, Thompson EJ, Kabanja J, Li J, Hu P, Gómez-Valero L, Silva FJ. (2009) Comparative sequence analysis of Mycobacterium leprae and the new leprosy-causing Mycobacterium lepromatosis. J Bacteriol 191:6067-74

 

Levis WR, Meeker HC, Schuller-Levis G, Sersen E, Schwerer B. (1986) IgM and IgG antibodies to phenolic glycolipid I from Mycobacterium leprae in leprosy: insight into patient monitoring, erythema nodosum leprosum, and bacillary persistence. J Invest Dermatol 86:529-34

 

Levis WR, Zhang S, Martiniuk F. (2012) Mycobacterium lepromatosis: emerging strain or species? J Drugs Dermatol 11:158

 

Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. (2013)  The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol  Jan 3 S1471-4906 [Epub ahead of print]

Martiniuk F, Giovinazzo J, Tan AU, Shahidullah R, Haslett P, Kaplan G and Levis WR. (2012) Lessons of leprosy: The emergence of TH17 cytokines during type II reactions (ENL) is teaching us about T-cell plasticity. J Drugs Derm 11:507-511

 

Modlin RL. (1994) Th1-Th2 paradigm: insights from leprosy. J Invest Dermatol 102:828-32

 

Rada E, Duthie MS, Reed SG, Aranzazu N, Convit J. (2011) Serologic follow-up of IgG responses against recombinant mycobacterial proteins ML0405, ML2331 and LID-1 in a leprosy hyperendemic area in Venezuela. Mem Inst Oswaldo Cruz 107 Suppl 1:90-4

 

Spencer JS, Duthie MS, Geluk A, Balagon MF, Kim HJ, Wheat WH, Chatterjee D, Jackson M, Li W, Kurihara JN, Maghanoy A, Mallari I, Saunderson P, Brennan PJ, Dockrell HM. (2012) Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy. Mem Inst Oswaldo Cruz 107 Suppl 1:79-89.

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