Ocular Syphilis and Cytomegalovirus Retinitis Have Different Immunologic Profiles

Previous research has shown that correlations between HIV infection, older age, lower CD4 counts, and the prevalence of ocular syphilis may suggest that development of the disease may be affected by immune status.

In a smaller study, Matilde Ruiz-Cruz, MD, MSc, a researcher at the Center for Research in Infectious Diseases at the National Institute of Respiratory Diseases (INER) in Mexico City, Mexico, characterized the immunologic profile in the aqueous (AqH) humor of HIV-infected patients who have cytomegalovirus retinitis (CMVr) or ocular syphilis, and they examined whether AqH and plasma represent independent cytokine compartments.

"Our results support previous findings indicating elevated levels of AqH IP-10 and MCP-1 in individuals with CMVr, and we corroborated the notion of elevated concentrations of MCP-1 and IL-8 previously reported in AqH of individuals with uveitis, as well as the intraocular production of IL-8 by the ciliary processes," the authors wrote.

Dr. Ruiz-Cruz and her colleagues measured concentrations of 27 cytokines in the AqH and plasma of 23 patients with CMVr and of 16 patients with ocular syphilis. The researchers enrolled the participants over a two-year period, and they measured and compared the cytokine profiles of patients in both groups.

The authors took plasma and AqH samples from participants before treating them for their ocular infection (OI). The medical workup for HIV-infected patients included CD4 T-cell counts and HIV RNA load determinations. To detect ocular involvement in HIV infection, the authors examined all patients with a slit-lamp biomicroscope and an indirect ophthalmoscope.

They diagnosed ocular infections on clinical exam. White retinal lesions, vasculitis, intraretinal hemorrhages, and retinal edema without vitritis indicated CMVr. Uveitis, retinitis, vitritis, choroiditis, papillitis, and panuveitis, with positive serum Venereal Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS) tests indicated ocular syphilis.

After the researchers obtained plasma and AqH samples, they treated the patients who had CMVr with oral valganciclovir and those who had ocular syphilis with intravenous penicillin.

They took 20 mL of peripheral ethylenediaminetetraacetic acid (EDTA) anticoagulated blood from HIV-infected patients. The plasma was centrifuged and separated, and it was stored at —80ºC for testing. Aqueous humor samples (100–150μL) were collected by anterior chamber puncture with a 30-gauge needle using topical anesthesia and were also stored at –80ºC.

As reported online January 12, 2017 in the journal, Ocular Immunology and Inflammation, patients with CMVr had higher plasma cytokine levels than those with ocular syphilis. Those with CMVr had higher plasma concentrations of interleukin (IL)-7, IL-8, IL-10, interferon (IFN)-γ, IFN-α2, G-CSF, IP-10 and IL-1α; they also had greater AqH concentrations of IL-1α, IP-10 and GM-CSF than participants with ocular syphilis. In both infections, AqH and plasma levels correlated only for IP-10.

"To our knowledge, this is the first study comparing the immunologic profile in AqH and plasma of HIV-infected individuals with CMVr versus those with ocular syphilis," the authors wrote.

"Individuals with CMVr have a more advanced HIV infection than individuals with ocular syphilis, and plasma cytokine concentrations seem to be determined mostly by the stage of HIV disease and in a lesser extent by the type of ocular infection," they added.

Because the immunologic profiles in aqueous humor and plasma are independent, the authors noted, aqueous humor cytokine concentrations cannot be inferred from plasma cytokine concentrations in these patients.

Identifying the cytokines involved in the pathogenesis of ocular infections in HIV-infected patients may lead to the development of drugs targeting these cytokines, especially in cases of inflammation that persists after active ocular infections have been successfully treated, they added.

Lorraine L. Janeczko, MPH, is a medical science writer who creates news, continuing medical education and feature content in a wide range of specialties for clinicians, researchers and other readers. She has completed a Master of Public Health degree through the Department of Epidemiology of the Johns Hopkins Bloomberg School of Public Health and a Dana Postdoctoral Fellowship in Preventive Public Health Ophthalmology from the Wilmer Eye Institute, the Johns Hopkins University School of Medicine and the Bloomberg School.