Detection of antibodies against homologous Mycobacterium avium subspecies paratuberculosis and beta-cell antigen zinc transporter 8 epitopes in Sardinian type 1 diabetic patients with proliferative diabetic retinopathy

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Abstract

Purpose

Diabetic retinopathy (DR) is the leading cause of new cases of blindness in developed countries. ZnT8, a beta-cell membrane protein involved in Zn++ transportation, may act as a major autoantigen in Type 1 Diabetes (T1D). Dysregulation in Zn++ homeostasis has been implicated in the pathogenesis of ischemia in DR. Mycobacterium avium subspecies paratuberculosis (MAP) causes an asymptomatic human infection transmitted from dairy herds through food contamination. MAP3865c, a MAP cell membrane protein, has been shown to display a relevant sequence homology with ZnT8. Moreover, antibodies recognizing MAP3865c epitopes have been found to cross-react with ZnT8 in T1D patients. The purpose of this study was to detect serum antibodies against 6 highly immunogenic MAP3865c epitopes in T1D patients with proliferative diabetic retinopathy (PDR) and in healthy controls (HCs).

Methods

Blood samples were obtained from 23 T1D patients with PDR and 39 HCs. Antibodies against 2 trans-membrane (MAP3865c125–133 MAP3865c133–141) and 4 C terminal (MAP3865c246–252, MAP3865c256–262, MAP3865c261–267 and MAP3865c281–287) peptides were detected by indirect ELISA. Fisher’s exact test and ROC curves were used to assess results.

Results

Antibodies against MAP3865c peptides were found in 6 out of 23 (26%) T1D patients with PDR and 2 out of 39 (5%) HCs, a statistically significant difference (p=0.04).

Conclusion

Results suggest that serum antibodies against MAP3865c peptides may play a role in the pathogenesis of PDR in T1D patients.Further larger studies are necessary to confirm these preliminary data.

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