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


CONCLUSIONS
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.
Makerere University College of Health Sciences, Uganda; Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: dnakanjako@gmail.com.
Damalie
D
Nakanjako
Makerere University College of Health Sciences, Uganda.
Juliet
J
Otiti-Sengeri
Infectious Disease Research Collaboration, Kampala, Uganda.
Isaac
I
Ssewanyana
Makerere University College of Health Sciences, Uganda.
Rose
R
Nabatanzi
Makerere University College of Health Sciences, Uganda.
Lois
L
Bayigga
Makerere University College of Health Sciences, Uganda.
Samuel
S
Kirimunda
Makerere University College of Health Sciences, Uganda.
Moses
M
Joloba
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Yukari C
YC
Manabe
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Andrew
A
Kambugu
University of Antwerp, Belgium; Institute of Tropical Medicine, Antwerp, Belgium.
Robert
R
Colebunders
Makerere University College of Health Sciences, Uganda.
Harriet
H
Mayanja-Kizza
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002386:Cataract / Q000209:etiology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014454:Uganda
D000954:Antigens, Surface
Aging; Blinding Cataracts; HIV/AIDS; Immune activation; Regulatory T-cells; Sub-Saharan Africa