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Anti-PGL-TB-1 Antibodies Predict Lack of Immune Restoration Syndrome in HIV Positive Patients with Tuberculosis

Immune restoration syndrome refers to acute worsening of disease symptoms in an HIV positive person infected with another infectious pathogen (such as tuberculosis) when effective antiretroviral therapy begins to restore immune function.

In a prospective, multicenter study, French researchers analyzed antibody responses and Mycobacterium tuberculosis clinical isolate genotypes in 24 consecutive HIV positive tuberculosis patients treated with HAART who either went on to develop a tuberculosis immune restoration syndrome (TB-IRS) or did not.

Circulating antibodies against ManLAM, ESAT-6/CFP10, and phenolic glycolipid TB (PGL-TB-1, a Mycobacterium tuberculosis-specific antigen) in HIV-TB coinfected patients were measured by ELISA at the initiation of anti-TB treatment, at initiation of HAART, and periodically thereafter.

The presence of circulating B-cells was also monitored by in vitro antibody production against ESAT-6/CFP10 and PGL-TB1. Finally, 16 out of 24 Mycobacterium tuberculosis clinical isolates from patients with TB-IRS were genotyped using spoligotyping and MIRUs-VNTR typing.

Results

11 of 24 patients (45.8%) experienced TB-IRS.

TB-IRS patients had significantly lower anti-PGL-TB1 antibody compared to those without TB-IRS prior to development of TB-IRS.

These very low levels were neither related to CD4 counts or complexed antibodies.

No differences in antibody levels were observed with the other tested antigens.

In addition, no specific TB strain genotype was associated with TB-IRS.

Conclusion

In conclusion, the study authors wrote, "The presence of specific anti-PGL-TB1 antibodies only in TB-IRS negative patients represents for the first time [emphasis added-Ed] an indicator of a potential protective response or a diagnostic biomarker for the detection of non-progression to TB-IRS in HIV-TB coinfected patients starting HAART."

Université Paris VII et Service de Microbiologie, Hôpital Saint-Louis, Assistance Publique--Hôpitaux de Paris, Paris, France.

6/06/08

Reference
N Simonney, G Dewulf, JL Herrmannn, and others. Anti-PGL-TB1 responses as an indicator of the immune restoration syndrome in HIV-TB patients. Tuberculosis (Edinb). May 19, 2008 [Epub ahead of print].

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NM Carroll and others. Prediction of delayed treatment response in pulmonary tuberculosis: Use of time to positivity values of Bactec cultures. Tuberculosis (Edinb). May 2, 2008 [Epub ahead of print].

N Simonney and others. B-cell immune responses in HIV positive and HIV negative patients with tuberculosis evaluated with an ELISA using a glycolipid antigen. Tuberculosis (Edinb) 87(2):109-22. March 2007.

FC Serra and others. Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro. Brazilian Journal of Infectious Diseases 11(5): 462-465. October 2007.

SA Clark and others. Tuberculosis antigen-specific immune responses can be detected using enzyme-linked immunospot technology in human immunodeficiency virus (HIV)-1 patients with advanced disease. Clin Exp Immunol 150(2): 238-244. November 2007.

A Bourgarit and others. Explosion of tuberculin-specific Th1-responses induces immune restoration syndrome in tuberculosis and HIV co-infected patients. AIDS 20(2): F1-7. January 9, 2006.

RA Breen and others. Does immune reconstitution syndrome promote active tuberculosis in patients receiving highly active antiretroviral therapy? AIDS 19(11): 1201-1206. July 22, 2005.




 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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