Experimental and Clinical Sciences International Journal 2014, 13:761-771

Serum protein electrophoresis under effective control of HIV-1 disease progression.

Adedeji AL1,3, Adenikinju RO2, Ajele JO3 and Olawoye TL3

1 Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria

2 Health Centre, Federal University of Technology, Akure, Nigeria

3 Department of Biochemistry, Federal University of Technology, Akure, Nigeria

 

ABSTRACT

In this report, we compared the Serum Protein Electrophoresis (SPE) patterns in a subset of HIV-1-infected subjects who did not progress to AIDS without antiretroviral treatment with those in whose control of disease progression was achieved by Highly Active Antiretroviral Therapy (HAART). SPE and immunofixation electrophoresis were performed on Helena Electrophoresis System according to manufacturer’s instructions. The percentage of SPE abnormalities, resembling chronic inflammation, was significantly higher in HIV-1-infected subject without HAART compared with those under HAART (p = 0.001). The majority of individuals under HAART showed evidence of oligoclonal bands on the γ-band against a polyclonal background compared with those without HAART but β-γ-band bridging was more evident. Immunofixation pattern was consistent with oligoclonal hypergammaglobulinaemia of IgG kappa type, which was found to be more intense in group without HAART. HIV clinical status did not show appreciable effect on the SPE pattern in subjects without HAART. However, under effective HAART, subjects with better CD4 T-cell count were associated with higher γ-globulin band. In group without HAART, acute infection was found to be associated the higher γ-globulin fraction compared with chronic infection. The opposite was the case under effective HAART. HIV infected subjects that did not progress to AIDS were associated with markedly abnormal SPE pattern. Overall results reflect the host ability to compensate defective cellular immunity in HIV-1 infection with humoral immune responses. These findings underscore the usefulness of SPE monitoring HIV disease management and identifying individuals that may not progress to full-blown AIDS in the absence of treatment.

 

SUPPLEMENTARY

Since the beginning of HIV pandemic, there have been concerted efforts aimed at understanding the pathogenesis of HIV disease. One of the landmarks has been the discovery of helper T-lymphocytes role and its subsequent use in the diagnosis, staging and management of the pandemic. Mature helper T lymphocytes express surface protein, CD4 and are called CD4+ T-lymphocytes (CD4+ T-cells). They generally possess pre-defined roles of expressing and secreting cytokines upon activation by peptides derived from pathogen. They thus “help” both cellular and humoral arms of immune system to function effectively (figure 1). Progression of HIV infection to AIDS is presaged by an increase in the rate of loss of CD4+ T-cells. Profound immunodeficiency is clinically manifested by opportunistic infections. Considerable variation exists in the time it takes for clinical disease to develop. A majority of persons without treatment normally succumb to an accelerated disease course, resulting in full-blown AIDS. The introduction of highly active antiretroviral therapy plays critical roles in suppressing viral replication and improving blood CD4+ T-cells levels. This translates to significant reduced AIDS related morbidity and mortality among HIV/AIDS patients. The chemotherapy also enhances protection against opportunistic infections.

Earlier (1), we observed significant variability in Serum Protein Electrophoresis (SPE) pattern in HIV infection; even in subjects within the same clinical status and humoral immune responses did not significantly correlate blood CD4+ T-cells count. The significance of this report is that different HIV infected subjects of the same clinical status has different ability to mount protective humoral immune responses against opportunistic infections. We also noted a subset of people living with HIV who did not progress to AIDS without treatment. In this related study (2), we use SPE, an underutilized technique in HIV disease management, to demonstrate the peculiar serum protein pattern of this subset. We discovered that HIV-infected subjects who did not progress to AIDS were associated with markedly abnormal SPE pattern. The abnormality is an elevated γ-globulin band of the electrophoregram. This phenomenon undoubtedly contributes to the ability to resist progression in the absence of treatment. In other words, despite impaired ability of CD4+ T-cells to “help” mount effective cellular responses, they still “help” to stimulate vigorous humoral responses, especially against opportunistic infections. Similarly, Van Duyne et al (3) have demonstrated that unique low molecular weight serum proteins are expressed in long term non-progressor HIV-1 patients and may contribute to the ability of these patients to combat HIV-1 infection in the absence of HAART. Stratification of this subset into sub-groups defined by CD4+ T-cells counts (< 500 or > 500 cells/μl) adds another dimension to the study. HIV clinical (CD4+ T-cells counts) status does not show appreciable effect on the SPE pattern, indicating that a mere blood CD4+ T-cells quantity cannot be employed in the assessment of immune status of this subset. We had observed similar phenomenon with serum β2-microglobulin activity in our earlier study (4).

Conclusively, two lessons are evident in this study. Persistent abnormally high γ-globulin fraction is associated with effective control of HIV disease progression. The γ-globulin pattern suggests polyclonal responses, perhaps, not only against HIV proteins but also opportunistic infectious agents. In a subset of some people living with HIV who did not progress to AIDS without treatment; the host ability to resist progression to AIDS is apparently not a function of the quantity of blood CD4+ T-cells.

 

f1Figure 1: Schematic diagram highlighting the roles of CD4+ T-cells in both cellular and humoral immune responses. The “help” rendered to B-cells were indirectly studied using serum protein electrophoresis.

 

ACKNOWLEDGEMENTS

We are grateful to the support group members, in Ilesa, Iwo and Ejigbo for participating in this study. Support of LIHOC staff members is gratefully appreciated. We also thank Professor JA Katzmann and Dr. KS Lockington (Protein Laboratory, Mayo Clinic, Rochester, USA) for their kind assistance in handling the densitometry of this work. The Principal Investigator, Professor TL Olawoye, acknowledges the financial support from Senate Research Grant (URC/MAJOR/168), Federal University of Technology, Akure, Nigeria.

References

  1. Adedeji AL, Olawoye TL and Osotimehin BO (2004): Electrophoretic pattern of serum proteins in Human Immunodeficiency Virus type 1 (HIV-1) infection. Nigerian Journal of Biochemistry and Molecular Biology 19(2):93-96.
  2. Adedeji AL, Adenikinju RO, AJele JO and Olawoye TL (2014): Electrophoretic profile of serum   proteins of HIV-1-infected Nigerians under effective control of HIV-1 disease progression Experimental and Clinical Sciences International Journal 13:761-771.
  3. Van Duyne R, Guendel I, Kehn-Hall K, Easley R, Klase Z, Liu C, Young M, Kashanchi F. (2010) The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients. AIDS Research and Therapy 7:21-37.
  4. Adedeji AL, Adeleke AB, Adekunle AS, Adebolu TT, Fakande I and Olawoye TL (2012): Effective control of HIV-1 disease progression: impact on serum concentration of β2-microglobulin. New York Science Journal 5(5):18-27.
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