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- Abolhassani, H, et al.
(författare)
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Expanding Clinical Phenotype and Novel Insights into the Pathogenesis of ICOS Deficiency
- 2020
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 40:2, s. 277-288
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundInducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novelICOSmutations resulting in a common variable immunodeficiency (CVID)–like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte–associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition.MethodsA combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and ICOS/ICOSL/CTLA4 expression following stimulation of whole blood and PBMCs with multiple TLR ligands, anti-CD3, and PHA.ResultsFour novel ICOS mutations included homozygous c.323_332del, homozygous c.451C>G, and compound heterozygous c.58+1G>A/c.356T>C. The predominant clinical phenotype was that of antibody deficiency associated with inflammatory complications in 4/7 patients. Six out of seven patients were treated with immunoglobulin replacement and one patient died from salmonella sepsis. All patients who were tested showed reduced IL-10 and IL-17 cytokine responses, normal IL-1β, IL6, and TNF release following LPS stimulation and highly elevated IL-12 production in response to combined LPS/IFNγ stimulation. This was associated with skewing of CD4+T cells towards Th1 phenotype and increased expression of ICOSL on monocytes. Lastly, reduced CTLA4 expression was found in 2 patients. One patient treated with ustekinumab for pancytopenia due to granulomatous bone marrow infiltration failed to respond to this targeted therapy.ConclusionsICOS deficiency is associated with defective T cell activation, with simultaneously enhanced stimulation of monocytes. The latter is likely to result from a lack of ICOS/ICOSL interaction which might be necessary to provide negative feedback which limits monocytes activation.
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| 3. |
- Rahmatian, B., et al.
(författare)
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Insight into tribocorrosion resistance and tribofilm formation on titanium boride coatings in a phosphate buffer saline solution
- 2023
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Ingår i: JOURNAL OF MATERIALS RESEARCH AND TECHNOLOGY-JMR&T. - : Elsevier BV. - 2238-7854. ; 27, s. 6847-6862
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Tidskriftsartikel (refereegranskat)abstract
- TiB2+TiB coatings were formed on Ti-6Al-4V through a molten-salt diffusional process at temperatures of 850 degrees C and 900 degrees C for 16 h. The thickness of the TiB layer increased by about two times at the higher process temperature, while the thickness of the TiB2 layer remained constant. Tribocorrosion rate of Ti-6Al-4V and the coated samples was evaluated in a reciprocating sliding under a normal load of 15 N in a phosphate buffer saline (PBS) solution for 3600-36000 cycles against an alumina ball. The results showed that the tribocorrosion rate of the borided samples decreased up to 56 times compared with Ti-6Al-4V after 36000 cycles. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies showed the presence of oxide-rich patches on the wear surface of Ti-6Al-4V with a thickness of up to 1 mu m. TEM and atomic force microscopy (AFM) images also revealed the presence of a tribofilm with a thickness of up to 200 nm on the surface of the boride coating. In addition, X-ray photoelectron spectroscopy (XPS) analysis confirmed the tribofilm formed on the wear surface of coated samples contained B2O3/H3BO3 compound, resulting in a more stable fluctuation in coefficient of friction and open circuit potential during sliding. The SEM images of the alumina wear surface showed cracks and titanium transfer layers in contact with the borided layers and Ti-6Al-4V, respectively.
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