NLRX1 inhibits the early stages of CNS inflammation and prevents the onset of spontaneous autoimmunity

Nucleotide-binding, leucine-rich repeat containing X1 (NLRX1) is a mitochondria-located innate immune sensor that inhibits major pro-inflammatory pathways such as type I interferon and nuclear factor-κB signaling. We generated a novel, spontaneous, and rapidly progressing mouse model of multiple sclerosis (MS) by crossing myelin-specific T-cell receptor (TCR) transgenic mice with Nlrx1−/− mice. About half of the resulting progeny developed spontaneous experimental autoimmune encephalomyelitis (spEAE), which was associated with severe demyelination and inflammation in the central nervous system (CNS). Using lymphocyte-deficient mice and a series of adoptive transfer experiments, we demonstrate that genetic susceptibility to EAE lies within the innate immune compartment. We show that NLRX1 inhibits the subclinical stages of microglial activation and prevents the generation of neurotoxic astrocytes that induce neuronal and oligodendrocyte death in vitro. Moreover, we discovered several mutations within NLRX1 that run in MS-affected families. In summary, our findings highlight the importance of NLRX1 in controlling the early stages of CNS inflammation and preventing the onset of spontaneous autoimmunity

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Clinical Presentation of Individuals With Human T-Cell Leukemia Virus Type-1 Infection in Spain

Background: Although only 8%-10% of persons infected with human T-cell leukemia virus type 1 (HTLV-1) may develop virus-associated diseases lifelong, misdiagnosis of asymptomatic infected carriers frequently leads to late diagnoses. Methods: A nationwide HTLV-1 register was created in Spain in 1989. A total of 351 infected persons had been reported by the end of 2017. We examined all new HTLV-1 diagnoses during the last decade and compared their clinical presentation. Results: A total of 247 individuals with HTLV-1 infection had been reported in Spain since year 2008. The incidence has remained stable with 20-25 new diagnoses yearly. Women represented 62%. Only 12% were native Spaniards, most of whom were foreigners from Latin America (72.5%). Up to 57 (23%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (n = 24; 42.1%), T-cell lymphoma (n = 19; 33.3%), or Strongyloides stercoralis infestation (n = 8; 14%). Human T-cell leukemia virus type 1 diagnosis had been made either at blood banks (n = 109; 44%) or at clinics (n = 138; 56%). It is interesting to note that Spaniards and especially Africans were overrepresented among patients presenting with HTLV-1-associated illnesses, suggesting that misdiagnosis and late presentation are more frequent in these populations compared to Latin Americans. Conclusions: Given that 23% of new HTLV-1 diagnoses in Spain are symptomatic, underdiagnosis must be common. Although screening in blood banks mostly identifies asymptomatic Latin American carriers, a disproportionately high number of Spaniards and Africans are unveiled too late, that is, they already suffer from classic HTLV-1 illnesses