RESUMO
The emergence of vaccine-derived polioviruses (VDPVs) in patients with Primary Immunodeficiency (PID) is a threat to the polio-eradication program. In a first of its kind pilot study for successful screening and identification of VDPV excretion among patients with PID in India, enteroviruses were assessed in stool specimens of 154 PID patients across India in a period of two years. A total of 21.42% of patients were tested positive for enteroviruses, 2.59% tested positive for polioviruses (PV), whereas 18.83% of patients were positive for non-polio enteroviruses (NPEV). A male child of 3 years and 6 months of age diagnosed with Hyper IgM syndrome was detected positive for type1 VDPV (iVDPV1) with 1.6% nucleotide divergence from the parent Sabin strain. E21 (19.4%), E14 (9%), E11 (9%), E16 (7.5%), and CVA2 (7.5%) were the five most frequently observed NPEV types in PID patients. Patients with combined immunodeficiency were at a higher risk for enterovirus infection as compared to antibody deficiency. The high susceptibility of PID patients to enterovirus infection emphasizes the need for enhanced surveillance of these patients until the use of OPV is stopped. The expansion of PID surveillance and integration with a national program will facilitate early detection and follow-up of iVDPV excretion to mitigate the risk for iVDPV spread.
RESUMO
OBJECTIVE: Metabolomics, the study of global alterations in small metabolites, is a useful tool to look for novel biomarkers. Recently, we reported a reprogramming of the serum metabolomic profile by nuclear magnetic resonance (NMR) spectroscopy following treatment in lupus nephritis (LN). This study aimed to compare the urine excretory levels of citrate and acetate in patients with biopsy-proven LN before and six months after cyclophosphamide induction therapy and to evaluate their correlation with the Systemic Lupus Erythematosus Disease Activity Index 2K (SLEDAI 2K) and renal SLEDAI. METHODS: Urine obtained from LN patients (N = 18, 16 female) at diagnosis and six months following induction therapy with cyclophosphamide and healthy controls (HC; N = 18, median age = 35 years, all female) were stored at -80°C. Metabolomic profiling was done using high resolution 800 MHz 1D 1H NMR spectroscopy. The urinary ratio of metabolites was calculated as (metabolite×1000)/creatinine. Disease activity was measured using the SLEDAI. Metabolomic profiles were compared between groups and correlated with clinical parameters. RESULTS: Compared to HC, LN patients had significantly lower median urinary citrate/creatinine levels (LN = 18.26, range 12.80-27.62; HC = 107.7, range 65.39-138.4; p < 0.0001) which significantly increased after six months of cyclophosphamide treatment (51.05, range 11.51-170.2; p = 0.03). LN patients also differed from HC by having a higher mean urinary acetate/creatinine ratio (LN = 17.44, range 11.6-32.7; HC = 9.61, range 7.97-13.71; p = 0.054) with a non-significant fall in values after six months of treatment. The Area under curve for differentiating LN from HC for urinary citrate was 0.9136, and urinary acetate was 0.6883. The urinary acetate levels correlated with SLEDAI (r = 0.337, p = 0.048). Urinary citrate levels correlated positively with C3 (r = 0.362, p = 0.03) and negatively with urine protein/creatinine (r = -0.346, p = 0.039). CONCLUSIONS: Urinary citrate, which reflects dampened aerobic glycolysis and oxidative phosphorylation, improved significantly and is a potential non-invasive biomarker for diagnosis and monitoring treatment response in LN.
