ObjectivesTo report the expanded neurological presentations and oncological associations of tripartite motif-containing protein 46 (TRIM46)-IgG seropositive patients.MethodsArchived sera/cerebrospinal fluid (CSF) were evaluated by tissue-based immunofluorescence assay to identify patients with identical axon initial segment (AIS)-specific staining pattern. Phage immunoprecipitation sequencing (PhIP-Seq) was used to identify the putative autoantigen.ResultsIgG in serum (17) and/or CSF (16) from 25 patients yielded unique AIS-specific staining on murine central nervous system (CNS) tissue. An autoantibody specific for TRIM46 was identified by PhIP-Seq, and autoantigen specificity was confirmed by transfected COS7 cell-based assay. Clinical information was available for 22 TRIM46-IgG seropositive patients. Fifteen were female (68%). Median age was 67 years (range 25–87). Fifteen (68%) patients presented with subacute cerebellar syndrome (six isolated; nine with CNS accompaniments: encephalopathy (three), brainstem signs (two), myelopathy (two), parkinsonism (one)). Other phenotypes included limbic encephalitis (three), encephalopathy with/without seizures (two), myelopathy (two). Eighteen (82%) had cancer: neuroendocrine carcinomas (9; pancreatic (3), small-cell lung (4), oesophagus (1), endometrium (1)), adenocarcinomas (6; lung (2), ovarian (2), endometrial (1), breast (1)), sarcoma (2) and gastrointestinal tumour (1). Neurological symptoms in three followed immune checkpoint inhibitor (ICI) administration.ConclusionsThis study supports TRIM46-IgG being a biomarker of paraneoplastic CNS disorders and expands the neurological phenotypes, oncological and ICI-related adverse event associations.

Although epidemiological trends in peanut allergy have been determined, there are limited data for changes in prevalence and clinical characteristics for other common food allergens. This study was performed to determine the trends in prevalence and clinical characteristics of physician-diagnosed pediatric food allergy (FA) at a large urban-based tertiary care center from 2003 to 2008. The electronic medical record system was searched to identify all unique patients with FA as a diagnosis for 2003 and 2008. Included patients had either a definite clinical reaction on ingestion and (1) a positive specific IgE or skin-prick test or (2) food-specific IgE of >90% specificity. Patients with allergies to cow's milk, eggs, fish, peanuts, sesame, shellfish, soy, tree nuts, and wheat were included. The percentage of FA clinic patients increased from 3 to 8% over 5 years. The severity of initial reactions to food also increased from 2003 to 2008 (p < 0.05). Mean initial food-specific IgE decreased from 52 kU/L in 2003 to 40 kU/L in 2003 (p = 0.002). The age at diagnosis decreased from 2003 to 2008 for cow's milk (2.64-1.36 years; p < 0.05) and fish (5.10-2.86 years; p < 0.05) allergies. Peanuts and shellfish were associated with anaphylaxis and severe symptoms in 2008. Clinical characteristics of food-allergic reactions in this large tertiary care center worsened in severity over 5 years and reactions were associated with a lower specific IgE at presentation for peanut and shellfish allergy. Clinical presentation of FA may change over time and this phenomenon warrants study to determine contributory factors.

Thyroid secretion rate was determined in four strains of inbred mice and two groups of F1 hybrids. In all genotypes the thyroid secretion rate was consistently but not significantly greater in males than in females. The average thyroid secretion rates, expressed as micrograms l-thyroxine/ 100 gm body weight with the standard errors for the males and females, were: A/Jax 2.13 ± 0.12 and 1.84 ± 0.10; BALB/c 2.44 ± 0.21 and 1.84 ± 0.12; C57BR/cd 3.35 ± 0.34 and 2.45 ± 0.11; C57BL/6 4.19 ± 0.64 µg. and 3.33 ± 0.34. The secretion rate for hybrids CAF1 and BBF1 males and females, respectively, were: 2.34 ± 0.185 and 1.84 ± 0.106; 3.79 ± 0.644 and 2.74 ± 0.268 µg/100 gm. C57BL strain and BBF1 hybrid had significantly higher secretion rates than all other groups. The results are consistent with the output rate values reported earlier by the same authors, and clearly indicate that thyroid activity is under genetic control.