Autoreactivity against HSP70 and recoverin in patients with congenital and acquired ocular toxoplasmosis

Abstract

Purpose : Disruption of the blood retinal barrier (BRB) by pathogens, may trigger autoreactivity against different ocular antigens such as recoverin, but also against ubiquitous proteins like HSP70, which may lead to clinical consequences. Interestingly, HSP70 of human and Toxoplasma gondii (Tg), have high identity (76%); moreover, cross reactivity of Anti-TgHSP70 against miceHSP70 has been proved.
We performed a prospective observational study to determine the presence of auto-antibodies against HSP70 and recoverin in serum of patients with ocular toxoplasmosis (OT) and the association with clinical findings.

Methods : Cases of acquired (n=11) and congenital (n=8) localized OT, as well as congenital neuro-ophthalmic (n=14) and cerebral toxoplasmosis (CCT) without OT (n=9) were included; subclinical patients (n=11) were also tested. IgG auto-antibodies to human HSP70 and recoverin were determined by indirect ELISA.
Reactivity index (RI=absorbance at 490nm/negative controls mean+3SD) >1 was considered positive. Clinical data were obtained from the ophthalmologic examination. Kruskal-Wallis ^κ, Mann-Whitney U^∞, Spearman correlation and Fisher’s exact test^Φ were performed for significance.

Results : Frequency of antibodies to both antigens was higher in neuro-ophthalmic than in localized OT groups and in congenital than in acquired infection (figures 1A, B). The RI values against recoverin correlated to those vs HSP70 (figure 1C).
Both auto-antibodies were significantly associated to ocular complications, there was no significant association with retinal lesions or visual acuity (table 1).

Conclusions : We found systemic auto-antibodies against HSP70 and recoverin. CNS involvement and congenital infection seem to be relevant for autoreactivity against both antigens; contrary to what we expected, anti-recoverin antibodies were found in patients with CCT but without OT; in this regard we found that hippocalcin a CNS specific protein shares >50% predicted B-epitopes with recoverin, thus, hippocalcin might be a possible target in patients with CNS involvement.
Although more cases must be recruited, our preliminary data suggest that disruption of the BRB is not the only explanation for autoreactivity in this context.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Figure 1. Reactivity index vs HSP70 (A) and recoverin (B) between groups (median CI). (C) Scattered plot showing high positive correlation between RI to HSP70 and RI to recoverin (r=0.915, p<0.0001).