Xenodiagnosis using Ixodes scapularis larvae was safe and well tolerated. Further studies are needed to determine the sensitivity of xenodiagnosis in patients with Lyme disease and the significance of a positive result. Clinical Trials Registration NCT01143558.
Patients with classic hydroa vacciniforme–like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more common in Asia and South America. The disease can progress to a systemic form that may result in fatal lymphoma. We report our 11-year experience with 16 HVLPD patients from the United States and England and found that whites were less likely to develop systemic EBV disease (1/10) than nonwhites (5/6). All (10/10) of the white patients were generally in good health at last follow-up, while two-thirds (4/6) of the nonwhite patients required hematopoietic stem cell transplantation. Nonwhite patients had later age of onset of HVLPD than white patients (median age, 8 vs 5 years) and higher levels of EBV DNA (median, 1 515 000 vs 250 000 copies/ml) and more often had low numbers of NK cells (83% vs 50% of patients) and T-cell clones in the blood (83% vs 30% of patients). RNA-sequencing analysis of an HVLPD skin lesion in a white patient compared with his normal skin showed increased expression of interferon-γ and chemokines that attract T cells and NK cells. Thus, white patients with HVLPD were less likely to have systemic disease with EBV and had a much better prognosis than nonwhite patients. This trial was registered at www.clinicaltrials.gov as #NCT00369421 and #NCT00032513.
This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression.
Background
The smallpox vaccine has more serious side effects associated with it than other live attenuated vaccines in use today. While studies have examined serum cytokines in primary vaccinees at 1 and 3-5 weeks after vaccination with the smallpox vaccine, serial measurements have not been performed nor have studies been performed in revaccinees.
Methods
We analyzed cytokine responses every other day for two weeks after vaccination in both primary vaccinees and revaccinees.
Results
Primary vaccinees had maximal levels of G-CSF on days 6-7 after vaccination, peak levels of TNF-α, sTNFR1, IFN-γ, IP-10, IL-6, and TIMP-1 on days 8 to 9 after vaccination, peak levels of sTNFR-2 and MIG on days 10 to 11 after vaccination, and peak levels of GM-CSF at days 12-13 after vaccination. Primary vaccinees were significantly more likely to have higher peak levels of IFN-γ, IP-10, and MIG after vaccination than revaccinees. Primary vaccinees were significantly more likely to have fatigue, lymphadenopathy, and headache compared with revaccinees and a longer duration of these symptoms as well as missed hours from work than revaccinees.
Conclusions
The increased symptoms observed in primary vaccinees compared with revaccinees paralleled the increases in serum cytokines in these individuals.
Conflict of interest: PJG and LTH have filed a provisional patent titled Antiphospholipid Antibodies for the Diagnosis of Lyme Disease. ARM has a patent (US 8,926,989) for an unrelated Lyme disease diagnostic.
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