Differential expression of carcinoembryonic antigen-related cell adhesion molecule-5 (CEACAM5) and dipeptidyl peptidase-4 (DPP4) with detection of Middle East respiratory syndrome-coronavirus in peripheral blood.

BACKGROUND: Middle East respiratory syndrome-coronavirus (MERS-CoV) utilizes CD26 (dipeptidyl peptidase-4) and CD66e or CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5) receptors for cell infection. Peripheral blood mononuclear cells (PBMCs) play a critical role in mounting adaptive immune response against the virus. This study was performed to assess the expression of CD26 and CD66e on PBMCs and their susceptibility to MERS-CoV infection. METHODS: Surface expression of CD26 and CD66e receptors on PBMCs from MERS-CoV patients (n = 20) and healthy controls (n = 20) was assessed by flow cytometry and the soluble forms were determined by enzyme-linked immunosorbent assay (ELISA). MERS-CoV UpE and Orf1a genes in PBMCs were detected by using Altona diagnostics reverse transcription polymerase chain reaction (RT-PCR) kit. RESULTS: Mean fluorescent intensity (MFI) of CD66e was significantly higher on CD4 + lymphocytes (462.4 ± 64.35 vs 325.1 ± 19.69; p < 0.05) and CD8 + lymphocytes (533.8 ± 55.32 vs 392.4 ± 37.73; p < 0.04) from patients with MERS-CoV infection compared to the normal controls. No difference in MFI for CD66e was observed on monocytes (381.8 ± 40.34 vs 266.8 ± 20.6; p = 0.3) between the patients and controls. Soluble form of CD66e among MERS-CoV patients was also higher than the normal controls (mean= 338.7 ± 58.75 vs 160.7 ± 29.49 ng/mL; p < 0.01). Surface expression of CD26 on PBMCs and its soluble form were no different between the groups. MERS-CoV was detected by RT-PCR in 16/20 (80%) patients from whole blood, among them 8 patients were tested in PBMCs, 4/8 (50%) patients were positive. CONCLUSION: Increased expression levels of CD66e (CEACAM5) may contribute to increased susceptibility of PBMCs to MERS-CoV infection and disease progression.

Assessment of Th1/Th2 cytokines among patients with Middle East respiratory syndrome coronavirus infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a member of the beta-coronavirus genus of zoonotic origin that emerged in the Arabian Peninsula and is associated with significant morbidity and mortality. This study was conducted to assess the plasma levels of cytokines to evaluate the Th1/Th2 status among 46 MERS-CoV-infected patients (19 asymptomatic and 27 symptomatic) and 52 normal healthy controls using a customized luminex kit. Comparative analysis of data between MERS-CoV-infected patients and normal healthy controls revealed that although no difference was observed between asymptomatic MERS-CoV patients and controls, the mean plasma levels of interleukin (IL)-10 (44.69 ± 40.04 pg ml-1 versus 14.84 ± 6.96 pg ml-1; P < 0.0001), IL-4 (22.46 ± 8.02 pg ml-1 versus 16.01 ± 9.97 pg ml-1; P < 0.0001), IL-5 (10.78 ± 2.86 pg ml-1 versus 8.06 ± 1.41 pg ml-1; P < 0.0001) and IL-13 (14.51 ± 3.97 pg ml-1 versus 11.53 ± 4.16 pg ml-1; P < 0.003) in MERS-CoV symptomatic patients were significantly higher than the normal controls. The mean plasma levels of interferon (IFN)-γ and IL-12 were no different among the study groups. The cytokine profile among symptomatic MERS-CoV-infected patients was skewed to a Th2 type immune response.