Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Homozygous and Compound Hetrozygous Mutation in 3 Turkish Family with Jervell and Lange-Nielsen Syndrome

Long QT syndrome is one of the most common congenital cardiac ion channeldisorder that the morbidity and mortality rate can be decreased by anearly diagnosis and proper treatment. Cardiac repolarization abnormalitythat is characterized by prolonged OT interval and propensity for ventriculartachycardia of the torsades de pointes type are characteristics of thedisease. This syndrome represents high risk for presyncope, syncope, cardiacarrest and sudden death. Jervell and Lange-Nielsen syndrome (JLNS)is recessive form of long QT syndromes with additional inding of profoundsensorineural hearing loss. JLNS has been shown to occur due to homozygousand compound heterozygous mutations in KCNQ1 or KCNE1. Pathogenicmutations in the KCNQ1 gene were detected in all our JLNS cases. Indexcases of 3 families were 2 month yr, 3.5 yr old female and 3-yr old malewho visited the hospital due to intrauterine bradicardia, recurrent seizures/syncope, cardiac murmur, respectively and had all congenital sensorineuraldeafness. Their electrocardiograms revealed a markedly prolonged QTinterval. The sequence analysis of the probands revealed the presence ofcompound heterozygous mutation ([(c.477+1G&gt;A) + (c.520C&gt;T, p.R174C)]and homozygous missence mutations (c.728 G&gt;A, p. R243H), (1097G&gt;A,p.R366Q), respectively. Heterozygous mutation in KCNQ1 was identiied onthe maternal, paternal and sibling sides. Homozygous mutation was identi-ied in 3-yr old male’s sister and cousin also. Interestingly even if her QT islong she had intact hearing. β-blocker therapy was initiated to all affectedones. Asymptomatic heterozygous family members were taken to a clinicalfollow up. Clinical and moleular indings will be discussed to further enlightenthe genotype-phenotype association