Do anti-Tricomonas vaginalis antibodies recognize HIV gp41?

Fiori, Pier Luigi; Rappelli, Paola

Author Information

Department of Biomedical Sciences, Division of Experimental and Clinical Microbiology, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

Sponsorship: This work was supported by grants of the University of Sassari (Progetto di Ricerca sul 60%) and by the MURST.

Received 27 April 2000; accepted: 5 May 2000.

Article Outline

The serological diagnosis of HIV infection is usually made on the basis of the detection of circulating antibodies specific for viral antigens gp41, gp120 and gp160. Despite using recombinant immunogenic oligopeptides, which improved the sensitivity and specificity of immunological tests, a number of both false-positive and false-negative reactions have been reported [1–4]. Although the emergence of new viral serotypes or recent infection could be responsible, at least partly, for the low sensitivity of serological assays in detecting early antibody responses, false-positive results could be explained by crossreactions with unrelated antigens. Spehar and Strand [5] recently demonstrated the crossreactivity of anti-gp41 murine monoclonal antibodies with the human cytoskeletal protein alpha-actinin, and antibodies reacting with both the immunodominant region of HIV gp41 and alpha-actinin have been found in the sera of HIV-infected individuals.

HIV infection is frequently associated with several sexually transmitted diseases [6], and circulating antibodies specific for sexually transmitted microorganisms are frequently found in the sera of patients affected by AIDS. Recently, a clinical and epidemiological association between trichomoniasis, one of the most common sexually transmitted diseases, and HIV infection was described [7,8]. Trichomoniasis is caused by the protozoon Trichomonas vaginalis, and is characterized by abnormal genital discharge in women [9]; infection is frequently asymptomatic and diagnosis is generally based on microscopic examination of vaginal samples, of a sensitivity lower than 70%. As a consequence, the worldwide prevalence of trichomoniasis is generally underestimated.

T. vaginalis induced humoral, secretory, and cellular immune responses in infected individuals [10], and a contemporary presence of antibodies specific for the protozoon and HIV occurred frequently, especially in high-risk individuals. In a serological study among women from a highly endemic area for trichomoniasis [11], we recently demonstrated that the major immunogen recognized by the sera of patients exposed to trichomonad infection was the protozoan alpha-actinin. Because the reactivity of anti-p41 monoclonal antibodies with the human form of the same protein has already been described, we wanted to verify the hypothesis of crossreaction between trichomonad alpha-actinin and HIV gp41, and if this were so, whether it could be related to the false-positive results described for HIV serological tests.

A total of 140 T. vaginalis-positive human sera (108 with specific IgG and 32 with IgM) were selected using immunoenzymatic tests. Sera were then tested for anti-HIV antibodies by using the Enzygnost kit (HIV1 and HIV2), (Behring, Marburg, Germany) and the Genelavia Mixt kit (HIV1 and HIV2), (Sanofi Pasteur, Paris, France). Both commercial kits detect antibodies for immunodominant peptide of gp41. Only three out of 108 sera with IgG anti-T. vaginalis, and one out of 32 with IgM, tested positive for HIV using both kits.

Another group of 20 sera, all HIV positive as detected by the same kits, was tested for reactivity with trichomonad alpha-actinin. None reacted with T. vaginalis alpha-actinin, as demonstrated in immunoblotting experiments using both total solubilized T. vaginalis proteins and a recombinant form of protozoan alpha-actinin. Finally, a pre-absorbtion of anti-HIV sera with trichomonad proteins did not abolish the binding of antibodies to viral antigens.

These data are in agreement with our previous results, demonstrating that both rabbit and human anti-T. vaginalis alpha-actinin antibodies do not react with the human form of the protein [12]. The specificity of the reaction was consistent with the molecular structure of alpha-actinin [12,13]. The central domain of the molecule, which contains the higher immunogenic regions [12], does not show homology with any other known alpha-actinins.

Our results demonstrate that antigenic mimicry between T. vaginalis and HIV does not occur, and that protozoan alpha-actinin does not express peptides resembling immunogenic portions of HIV gp41. In conclusion, our data demonstrate that the presence of anti-T. vaginalis alpha-actinin antibodies in human sera does not represent a possible source of false-positive results when testing anti-HIV sera reactivities.

Pier Luigi Fiori

Paola Rappelli

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