Case Report: A child with NFKB1 haploinsufficiency explaining the linkage between immunodeficiency and short stature.

We report the case of a patient with common variable immunodeficiency (CVID) presenting with short stature and treated with recombinant human growth hormone (rhGH). Whole exome sequencing revealed a novel single-nucleotide duplication in the NFKB1 gene (c.904dup, p.Ser302fs), leading to a frameshift and thus causing NFKB1 haploinsufficiency. The variant was considered pathogenic and was later found in the patient's mother, also affected by CVID. This is the first reported case of a patient with CVID due to NFKB1 mutation presenting with short stature. We analyzed the interconnection between NFKB1 and GH - IGF-1 pathways and we hypothesized a common ground for both CVID and short stature in our patient.

Evaluation of a novel particle-based assay for detection of autoantibodies in idiopathic inflammatory myopathies.

BACKGROUND: Myositis specific antibodies (MSA) represent not only important diagnostic tools for idiopathic inflammatory myopathies (IIM), but also help to stratify patients into subsets with particular clinical features, treatment responses, and disease outcome. Consequently, standardization of MSA is of high importance. Although many laboratories rely on protein immunoprecipitation (IP) for the detection of MSA, IP standardization is challenging and therefore reliable alternatives are mandatory. Recently, we identified significant variation between IP and line immunoassay (LIA) for the detection of MSA and myositis associated antibodies. In this study we aimed to compare the results from our previous study to the results obtained with a novel fully automated particle-based technology for the detection of MSA and MAA. METHODS: A total of 54 sera from patients with idiopathic inflammatory myopathy (IIM) were tested using three methods: IP, LIA (Euroimmun, Germany) and a novel particle-based multi-analyte technology (PMAT, Inova Diagnostics, US, research use only). The analysis focused on antibodies to EJ, SRP, Jo-1, NXP-2, MDA5, TIF1-γ, and Mi-2. RESULTS: Significant variations were observed among all methods. Overall, the novel PMAT assays showed slightly better correlation with IP, but the kappa agreement was strongly dependent on the antibody tested. When the results obtained from IP were used as reference for receiver operating characteristic (ROC) curve analysis, good discrimination and a high area under the curve (AUC) value were found for PMAT (AUC = 0.83, 95% confidence interval, CI 0.70-0.95) which was significantly higher (p = .0332) than the LIA method (AUC = 0.70, 95% CI 0.56-0.84). CONCLUSION: The novel PMAT used to detect a spectrum of MSA in IIM represents a potential alternative to IP and other diagnostic assays. Additional studies based on larger cohorts are needed to fully assess the performance of the novel PMAT system for the detection of autoantibodies in myositis.

First report of anti-TIF1γ dermatomyositis in a patient with myelodysplastic syndrome.

Inflammatory myopathies as para-neoplastic phenomena were first described by Sterz in 1916. Recently, myositis specific autoantibodies were described in cancer-associated myositis. Anti-transcription intermediary factor 1 gamma (anti-TIF1γ) antibodies have been found in both young adults affected by juvenile dermatomyositis and in elderly patients with cancer-associated myositis. In this regard, we report herein the first case of anti-TIF1γ dermatomyositis secondary to a myelodysplastic syndrome.