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A subgroup of lupus patients with nephritis, innate T cell activation and low vitamin D is identified by the enhancement of circulating MHC class I-related chain A
- Source :
- Clin Exp Immunol
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- Summary The major histocompatibility complex (MHC) class I-related chain A (MICA) is induced upon stress, and labels malfunctioning cells for their recognition by cytotoxic lymphocytes. Alterations in this recognition and also abnormal natural killer (NK) functions have been found in systemic lupus erythematosus (SLE). MICA can be shed from cells, subsequently acting as a soluble decoy receptor (sMICA). Our purpose was to study circulating sMICA levels in relationship with the activation of innate pathways in PBMC in a cohort of lupus patients. NK cells were characterized by flow cytometry. Gene expression of Toll-like receptors (TLR), interferon (IFN)-I sensitive genes and MICA were separately analyzed in monocytes, T cells and B cells. Serum sMICA was measured with enzyme-linked immunosorbent assay (ELISA). In our cohort, NK cell counts dropped in relationship with disease activity. sMICA showed an inverse trend with NK cell counts, as well as a significant association with activity indices, but not with complement decrease. Levels of sMICA associated to proteinuria and active nephritis. A multivariate regression model revealed anti-nuclear antibody (ANA) titres, the up-regulation of TLR-4 in T cells and lower vitamin D as predictors of sMICA enhancement. Interestingly, vitamin D showed an inverse association with proteinuria and a strong correlation with T cell MICA mRNA levels. According to our data, circulating sMICA identifies a subgroup of lupus patients with low vitamin D, innate activation of T cells and nephritis. We propose that lymphocyte shedding could account for the enhancement of sMICA and reflect an immune evasion mechanism driving disease activation in lupus.
- Subjects :
- Adult
Male
0301 basic medicine
Adolescent
T cell
Lymphocyte
Immunology
Lupus nephritis
Lymphocyte Activation
Major histocompatibility complex
Young Adult
03 medical and health sciences
0302 clinical medicine
Immune system
medicine
Humans
Lupus Erythematosus, Systemic
Immunology and Allergy
Cytotoxic T cell
Vitamin D
Aged
Systemic lupus erythematosus
biology
business.industry
Histocompatibility Antigens Class I
Original Articles
Middle Aged
medicine.disease
Lupus Nephritis
Immunity, Innate
Up-Regulation
Killer Cells, Natural
Cross-Sectional Studies
030104 developmental biology
medicine.anatomical_structure
biology.protein
Female
Antibody
business
Biomarkers
030215 immunology
Subjects
Details
- ISSN :
- 13652249 and 00099104
- Volume :
- 196
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Immunology
- Accession number :
- edsair.doi.dedup.....9b8d6043d826c0268c2a3f95accd3687