CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda

Damalie Nakanjako; Juliet Otiti-Sengeri; Isaac Ssewanyana; Rose Nabatanzi; Lois Bayigga; Samuel Kirimunda; Moses Joloba; Yukari C. Manabe; Andrew Kambugu; Robert Colebunders; Harriet Mayanja-Kizza

doi:10.1016/j.imlet.2014.04.011

CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda

Damalie Nakanjako, Juliet Otiti-Sengeri, Isaac Ssewanyana, Rose Nabatanzi, Lois Bayigga, Samuel Kirimunda, Moses Joloba, Yukari C. Manabe, Andrew Kambugu, Robert Colebunders, Harriet Mayanja-Kizza

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Background: Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults. Methods: In a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adults-without-cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+^Bright and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups. Results: Of 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44-53) years] than HIV-negative [70 (IQR 59-75) years]; p= 0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p= 0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p= 0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p= 0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p<. 0.0001. Conclusion: CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.

Original language	English (US)
Pages (from-to)	44-49
Number of pages	6
Journal	Immunology Letters
Volume	161
Issue number	1
DOIs	https://doi.org/10.1016/j.imlet.2014.04.011
State	Published - Sep 2014
Externally published	Yes

Keywords

Aging
Blinding Cataracts
HIV/AIDS
Immune activation
Regulatory T-cells
Sub-Saharan Africa

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.imlet.2014.04.011

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Nakanjako, D., Otiti-Sengeri, J., Ssewanyana, I., Nabatanzi, R., Bayigga, L., Kirimunda, S., Joloba, M., Manabe, Y. C., Kambugu, A., Colebunders, R., & Mayanja-Kizza, H. (2014). CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda. Immunology Letters, 161(1), 44-49. https://doi.org/10.1016/j.imlet.2014.04.011

Nakanjako, D, Otiti-Sengeri, J, Ssewanyana, I, Nabatanzi, R, Bayigga, L, Kirimunda, S, Joloba, M, Manabe, YC, Kambugu, A, Colebunders, R & Mayanja-Kizza, H 2014, 'CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda', Immunology Letters, vol. 161, no. 1, pp. 44-49. https://doi.org/10.1016/j.imlet.2014.04.011

@article{a83c1c57d0c7478b91634ef5bafb58fa,

title = "CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda",

abstract = "Background: Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults. Methods: In a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adults-without-cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+Bright and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups. Results: Of 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44-53) years] than HIV-negative [70 (IQR 59-75) years]; p= 0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p= 0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p= 0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p= 0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p<. 0.0001. Conclusion: CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.",

keywords = "Aging, Blinding Cataracts, HIV/AIDS, Immune activation, Regulatory T-cells, Sub-Saharan Africa",

author = "Damalie Nakanjako and Juliet Otiti-Sengeri and Isaac Ssewanyana and Rose Nabatanzi and Lois Bayigga and Samuel Kirimunda and Moses Joloba and Manabe, {Yukari C.} and Andrew Kambugu and Robert Colebunders and Harriet Mayanja-Kizza",

note = "Funding Information: The authors acknowledge the study participants from Rakai Health Science Project and the Infectious Diseases Institute (IDI) rural HIV treatment cohorts. In addition, the authors acknowledge the Gladstone Institute of Vaccinology and Immunology (GIVI) at UCSF and the Vaccine and Gene Therapy Institute (VGTI), Florida where Damalie Nakanjako received training in multicolour flow cytometry during her post-doctoral training. This study was funded by the Belgian Government grant through the Belgium Technical Cooperation's “Own Initiatives 2007” Vlamse Interuniversitaire Raad (VLIR) Interuniversity Cooperation award to Institute of Tropical Medicine (ITM), University of Antwerp/Makerere University titled “Capacity Building in Clinical Research in Infectious Diseases” ( VLIR Reference ZEIN2007PR335 ) and a Wellcome Trust Uganda post-doctoral Fellowship in Infection and Immunity held by Damalie Nakanjako, funded by a Wellcome Trust Strategic Award , grant number 084344 .",

year = "2014",

month = sep,

doi = "10.1016/j.imlet.2014.04.011",

language = "English (US)",

volume = "161",

pages = "44--49",

journal = "Immunology Letters",

issn = "0165-2478",

publisher = "Elsevier",

number = "1",

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TY - JOUR

T1 - CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda

AU - Nakanjako, Damalie

AU - Otiti-Sengeri, Juliet

AU - Ssewanyana, Isaac

AU - Nabatanzi, Rose

AU - Bayigga, Lois

AU - Kirimunda, Samuel

AU - Joloba, Moses

AU - Manabe, Yukari C.

AU - Kambugu, Andrew

AU - Colebunders, Robert

AU - Mayanja-Kizza, Harriet

N1 - Funding Information: The authors acknowledge the study participants from Rakai Health Science Project and the Infectious Diseases Institute (IDI) rural HIV treatment cohorts. In addition, the authors acknowledge the Gladstone Institute of Vaccinology and Immunology (GIVI) at UCSF and the Vaccine and Gene Therapy Institute (VGTI), Florida where Damalie Nakanjako received training in multicolour flow cytometry during her post-doctoral training. This study was funded by the Belgian Government grant through the Belgium Technical Cooperation's “Own Initiatives 2007” Vlamse Interuniversitaire Raad (VLIR) Interuniversity Cooperation award to Institute of Tropical Medicine (ITM), University of Antwerp/Makerere University titled “Capacity Building in Clinical Research in Infectious Diseases” ( VLIR Reference ZEIN2007PR335 ) and a Wellcome Trust Uganda post-doctoral Fellowship in Infection and Immunity held by Damalie Nakanjako, funded by a Wellcome Trust Strategic Award , grant number 084344 .

PY - 2014/9

Y1 - 2014/9

N2 - Background: Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults. Methods: In a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adults-without-cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+Bright and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups. Results: Of 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44-53) years] than HIV-negative [70 (IQR 59-75) years]; p= 0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p= 0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p= 0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p= 0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p<. 0.0001. Conclusion: CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.

AB - Background: Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults. Methods: In a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adults-without-cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+Bright and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups. Results: Of 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44-53) years] than HIV-negative [70 (IQR 59-75) years]; p= 0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p= 0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p= 0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p= 0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p<. 0.0001. Conclusion: CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.

KW - Aging

KW - Blinding Cataracts

KW - HIV/AIDS

KW - Immune activation

KW - Regulatory T-cells

KW - Sub-Saharan Africa

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CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda

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