Intraocular viral and immune pathogenesis of immune recovery uveitis in patients with healed cytomegalovirus retinitis.
OBJECTIVE
To investigate immune and viral contributions to the pathogenesis of immune recovery uveitis (IRU), which presents as vitritis, macular edema, or formation of epiretinal membranes, and develops in patients with acquired immunodeficiency syndrome (AIDS) who experienced cytomegalovirus (CMV) retinitis before antiretroviral treatment (ART) induced immune reconstitution.


METHODS
Aqueous and vitreous fluids from patients with IRU, active CMV retinitis, and control human immunodeficiency virus (HIV)-negative, noninflamed eyes were compared for presence of cytokines IL-6, IL12, interferon gamma using enzyme-linked immunosorbent assay techniques, and CMV DNA (by polymerase chain reaction).


RESULTS
IRU eyes (11 patients, 18 samples) had the highest levels of IL-12 (median 48 pg/mL), moderate levels of IL-6 (median 146 pg/mL), and low but significant interferon gamma (median 15 pg/mL), compared to controls (P < 0.01). All uveitis eyes tested (9/9) were CMV DNA negative. In contrast, active CMV retinitis eyes were CMV DNA positive, had higher levels of IL-6 (median 349 pg/mL) (25 patients, 41 samples) than both control (P = 0.0001) and uveitis eyes (P = 0.048), similar levels of interferon gamma (median 27 pg/mL) to uveitis eyes, but less IL-12 (median 0 pg/mL) than uveitis eyes.


CONCLUSIONS
Inflammatory IRU can be differentiated from active CMV retinitis by the presence of IL-12, less IL-6, and absence of detectable CMV replication.
Division of Infectious Diseases, Department of Pathology, University of California-San Diego, UCSD Medical Center, MC 8416, 200 W. Arbor Drive, San Diego, CA 92103-8416, USA. rschrier@ucsd.edu
Rachel D
RD
Schrier
Mi-Kyoung
MK
Song
Irene L
IL
Smith
Marietta P
MP
Karavellas
Dirk-Uwe
DU
Bartsch
Francesca J
FJ
Torriani
Claudio R
CR
Garcia
William R
WR
Freeman
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000821:virology; D001082:Aqueous Humor / Q000378:metabolism / Q000821:virology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D003587:Cytomegalovirus / Q000502:physiology*; D017726:Cytomegalovirus Retinitis / Q000276:immunology* / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D018023:HIV Seronegativity / Q000276:immunology; D006801:Humans; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D014605:Uveitis / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication; D014822:Vitreous Body / Q000378:metabolism / Q000821:virology
D016207:Cytokines; D004279:DNA, Viral