We studied ten individuals from eight families showing features consistent with the immuno-osseus dysplasia spondyloenchondrodysplasia (SPENCD). Of particular note was the diverse spectrum of autoimmune phenotypes observed in these patients, including systemic lupus erythematosus (SLE), Sjögren's syndrome, haemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease, and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13 and linkage analysis yielded a combined multipoint lod score of 3.6. Sequencing of the ACP5 gene, encoding tartrate resistant acid phosphatase (TRAP), identified biallelic mutations in each of the patients studied, and in vivo testing confirmed a loss of expressed protein. All eight patients assayed demonstrated elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognised link between TRAP activity and interferon metabolism, and highlight the importance of type I interferon in the genesis of autoimmunity.

PurposeSpondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.MethodsWe compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations.ResultsWe observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy.ConclusionsOur data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.

Background Mosquitoes biolarvicides remain the most important method for mosquito control. The previous studies have shown Aspergillus sp. -expressed larvicidal properties against mosquito species. The present study evaluated larvicidal and histopathological effect of an endophytic fungus Aspergillus tamarii isolated from theCactus stem ( Opuntia ficus-indica Mill) . Method The molecular identification of isolated A. tamarii was done by PCR amplification (5.8s rDNA) using a universal primer (ITS-1 and ITS-2). The secondary metabolites of A. tamarii was tested for larvicidal activity against Aedes aegypti and Culex quinquefasciatus . Larvicidal bioassay of different concentrations (- 100, 300, 500, 800 and 1000 μg/mL) isolated extracts were done according to the modified protocol. Each test included a set of control groups (i.e. DMSO and distilled water). The lethal concentrations (LC 50 and LC 90 ) were calculated by probit analysis. Experimental monitoring duration was 48 h. Results The ethyl acetate extract from A. tamarii fungus resulted - excellent mosquitocidal effect against Ae. aegypti and Cx. quinquefasciatus mosquitoes, with least LC 50 and LC 90 values. -After 48 h, the Ae. aegypti expressed better results (LC 50 = 29.10, 18.69, 16.76, 36.78 μg/mL and the LC 90 = 45.59, 27.66, 27.50, 54.00 μg/mL) followed by Cx. quinquefaciatus (LC 50 = 3.23, 24.99, 11.24, 10.95 μg/mL and the LC 90 = 8.37, 8.29, 21.36, 20.28 μg/mL). The biochemical level of A. tamarii mycelium extract on both larvae was measured and the results shown a dose dependent activity on the level of AchE, α- and β-carboxylesterase assay. Gas Chromatography and Mass Spectroscopy (GC-MS) profile of A. tamarii extract reflected three compounds i.e. preg-4-en-3-one, 17. α-hydroxy-17. β-cyano- (7.39%), trans-3-undecene-1,5-diyne (45.77%) and pentane, 1,1,1,5-tetrachloro- (32.16%) which which might had attributed to larvae mortality. Conclusion The findings of - present study shows that the use of endophytic A. tamarii fungal metabolites for control of dengue and filariasis vectors is promising and needs a semifield and small scale filed trials.

We treated a 5-year-old boy, in our hospital in south India, who had a history of recurrent respiratory infections, tuberculosis, and severe varicella infection. He was short in build and a radiological examination revealed evidence of spondylometaphyseal dysplasia. Investigation of the immune system was suggestive of compromised cellular immunity. Immunofluorescence and immunoblot assay for antibodies detected underlying multiple disorders such as systemic lupus erythematosus (SLE), autoimmune thrombocytopenia, and juvenile rheumatoid arthritis (JRA). Roifman et al. described a similar syndrome in 2000 and 2003, which was characterized by spondylometaphyseal dyplasia, combined immunodeficiency, and autoimmunity and called it Roifman-Costa syndrome (OMIM 607944). Hence a diagnosis of Roifman-Costa syndrome was made. Ours shall be the first report of such a condition from the Indian subcontinent and hence the communication.

Human coronary artery smooth muscle cells (HCASMCs) play an important role in the pathogenesis of coronary atherosclerosis and coronary artery diseases (CAD). Serotonin is a mediator known to produce vascular smooth muscle cell (VSMC) mitogenesis and contribute to coronary atherosclerosis. We hypothesize that the human coronary artery smooth muscle cell possesses certain functional constituents of the serotonergic system such as: tryptophan hydroxylase and serotonin transporter. Our aim was to examine the presence of functional tryptophan hydroxylase-1 (TPH1) and serotonin transporter (SERT) in HCASMCs. The mRNA transcripts by qPCR and protein expression by Western blot of TPH1 and SERT were examined. The specificity and accuracy of the primers were verified using DNA gel electrophoresis and sequencing of qPCR products. The functionality of SERT was examined using a fluorescence dye-based serotonin transporter assay. The enzymatic activity of TPH was evaluated using UPLC. The HCASMCs expressed both mRNA transcripts and protein of SERT and TPH. The qPCR showed a single melt curve peak for both transcripts and in sequence analysis the amplicons were aligned with the respective genes. SERT and TPH enzymatic activity was present in the HCASMCs. Taken together, both TPH and SERT are functionally expressed in HCASMCs. These findings are novel and represent an initial step in examining the clinical relevance of the serotonergic system in HCASMCs and its role in the pathogenesis of coronary atherosclerosis and CAD.