Younger Age and Albuminuria are Associated with Proliferative Diabetic Retinopathy and Diabetic Macular Edema in the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study.

Purpose: The purpose of the South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) Study is to identify non-genetic and genetic risk factors associated with diabetic retinopathy (DR). This report examines the non-genetic risk factors for DR in South Indian patients.Methods: Participants with South Indian ancestry and type 2 diabetes (T2D) were included from two sources: the Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study (SN-DREAMS) and prospective recruitment at Sankara Nethralaya affiliates. Fundus photography and optical coherence tomography (OCT) were obtained on participants. Fundus images were graded for DR severity and OCTs were graded for center-involved diabetic macular edema (ciDME). Multivariate analyses were performed using stepwise logistic regression to assess effects of the demographic and clinical factors on proliferative DR (PDR) and DME.Results: Among the 2941 participants with DR grading, participants with PDR were more likely to be younger [odds ratio (OR)=0.95], men (OR = 1.83), have a longer duration of diabetes (OR = 1.10), have a higher hemoglobin A1c (OR = 1.12), have albuminuria (OR = 5.83), have hypertension (OR = 1.69), have a higher HDL (OR = 1.02) and a lower total cholesterol (OR = 0.99) (all p < 0.05). Among the 483 participants with gradable OCT scans, participants who had ciDME were more likely to be younger (OR = 0.97), men (OR = 2.80), have a longer duration of diabetes (OR = 1.06), have lower triglycerides (OR = 0.99), and have albuminuria (OR = 3.12) (all p < 0.05).Conclusions: Younger age, male sex, longer duration of diabetes, higher HbA1c, and presence of albuminuria were identified as risk factors for PDR and DME in a South Indian population with T2D.

Neonatal and maternal immunological responses to conserved epitopes within the DBL-gamma3 chondroitin sulfate A-binding domain of Plasmodium falciparum erythrocyte membrane protein 1.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the adherence of P. falciparum-infected erythrocytes to placental syncytiotrophoblasts via interactions with chondroitin sulfate A (CSA), a characteristic of pregnancy-associated malaria. Pregnancy-associated malaria predicts increased susceptibility of newborns to malaria, and it is postulated that transplacental passage of parasite antigen induces immune regulatory activity in the neonate. We wished to examine the immune responsiveness to a CSA-binding domain of PfEMP1, the DBL-gamma3 domain, in cord and maternal venous blood obtained from pregnancies with various histories of P. falciparum infection. We assessed in vitro T-cell cytokine and plasma immunoglobulin G (IgG) and IgM responses to four peptides corresponding to highly conserved regions of a DBL-gamma3 domain common to central African parasite isolates. The presence of placental P. falciparum infection at delivery was associated with elevated frequencies of DBL-gamma3 peptide-specific CD3+ interleukin-10-positive T cells in cord blood, while treatment and clearance of infection prior to delivery was associated with elevated frequencies of CD3+ gamma interferon-positive T cells. DBL-gamma3 peptide-specific IgM antibodies were detected in 12 of 60 (20%) cord plasma samples from those born to mothers with P. falciparum infection during pregnancy. Consistent with polyclonal anti-PfEMP1 antibody responses that are associated with protection against pregnancy-associated malaria, the presence of maternal IgG antibodies with specificity for one of the DBL-gamma3 peptides showed a parity-dependent profile. These data demonstrate that peptides corresponding to conserved regions of the DBL-gamma3 domain of PfEMP1 are immunogenic in P. falciparum-infected mothers and their offspring.