Bhasym, Angika and Gurjar, Bahadur Singh and Prabhu, Savit and Puraswani, Mamta and Khandelwal, Priyanka and Saini, Himanshi and Saini, Savita and Chatterjee, Priyadarshini and Bal, Vineeta and George, Anna and Coshic, Poonam and Patidar, Gopal and Hari, Pankaj and Sinha, Aditi and Bagga, Arvind and Rath, Satyajit and Guchhait, Prasenjit (2019) Altered Peripheral Blood Leucocyte Phenotype and Responses in Healthy Individuals with Homozygous Deletion of FHR1 and FHR3 Genes. Journal of Clinical Immunology, 39 (3). pp. 336-345. ISSN 0271-9142

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Abstract

A homozygous 83-kb deletion encompassing the genes for complement factor-H-related proteins 1 and 3 (FHR 1, FHR3) is known as a risk factor for some immune inflammatory disorders. However, the functional relevance of this FHR1/3 deletion is relatively unexplored. Globally, healthy populations of all ethnic groups tested show an 8–10% prevalence of homozygosity for this deletion polymorphism. We have begun to compare the peripheral leucocyte phenotype and functionality between FHR1/3−/− and FHR1/3+/+ healthy adult individuals. We report that the two groups show significant differences in their peripheral blood innate leucocyte subset composition, although the adaptive immune subsets are similar between them. Specifically, FHR1/3−/− individuals show higher frequencies of patrolling monocytes and lower frequencies of classical monocytes than FHR1/3+/+ individuals. Similarly, FHR1/ 3−/− individuals show higher frequencies of plasmacytoid dendritic cells (pDCs) and lower frequencies of myeloid DCs (mDCs) than FHR1/3+/+ individuals. Notably, classical monocytes specifically showed cell-surface-associated factor H (FH), and cells from the FHR1/3−/− group had somewhat higher surface-associated FH levels than those from FHR1/3+/+ individuals. FHR1/3−/− monocytes also showed elevated secretion of TNF-α, IL-1β, and IL-10 in response to TLR7/8 or TLR4 ligands. Similarly, FHR1/3−/− mDCs and pDCs showed modest but evident hyperresponsiveness to TLR ligands. Our findings, that the FHR1/3−/− genotype is associated with significant alterations of both the relative prominence and the functioning of monocyte and DC subsets, may be relevant in understanding the mechanism underlying the association of the genotype with immune inflammatory disorders.

Item Type:	Article
Subjects:	Biomedical Science
Depositing User:	RCB Library
Date Deposited:	14 Mar 2023 10:12
Last Modified:	14 Mar 2023 10:12
URI:	http://rcb.sciencecentral.in/id/eprint/288

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