Analysis of neutralizing antibodies to Enterovirus 70 and Coxsackievirus A24 variant, levels of immunoglobulins and total protein in tears of patients with acute hemorrhagic conjunctivitis

Tear samples were collected from 37 residents of the Dominican Republic <5 d post onset (p.o.) of symptoms (mean 1.73±1.17 d p.o.) of acute hemorrhagic conjunctivitis (AHC). Sixty-two percent (23/37) of the patients had bilateral infections. Anti-enterovirus 70 (EV70) tear neutralizing activity (TNA) (10(2->3.5) U/ml) and anti-Coxsackievirus A24 variant (CA24v) TNA (10(<1-3) U/ml), but no anti-poliovirus (PV) TNA was detected. The anti-EV70 TNA in pooled tear samples sedimented in sucrose density gradient fractions that corresponded to 19-7S serum anti-PV immunoglobulin (1g). Anti-CA24v TNA sedimented as 7S1g. 1gG levels (mean, 3.13±4.2mg/ml) were higher than 1gA levels (mean, 0.92±0.98 mg/ml) in 21 of 27 tear samples. 1gG levels in tears from six patients with bilateral AHC were associated with total tear protein (p=0.003), but not with the levels of TNA or interferon (IFN). The total protein in AHC tears (5.13±1.72 mg/ml) was two-fold less than the total protein in normal tears (11.2±3.25 mg/ml). 1gA levels increased from 0.31±.3 to 1.34±1.28 mg/ml in tears collected up to 3 d p.o. of AHC. 1gM was not detected (<0.01 mg/ml). EV70 was isolated from the tears of one patient. Taken together, our results suggest that EV70 and CA24v are endemic in the Dominican Republic and that the 1992 epidemic of AHC was due to EV70. The detection of 19S (IgM) and high levels of 7S (IgG) TNA to EV70<1 d p.o. of AHC indicate a rapid ocular immune response to EV70 and suggests that virus-specific TNAs inhibit AHC virus infection.