title: Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis.
abstract: Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-γ, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-γ, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-γ also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-γ up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path-physiology of RA.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. rpahwa@ucdavis.edu.com.
authors.forename: Roma
authors.initials: R
authors.lastname: Pahwa
authors.affiliation: Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. nibhriti@hotmail.com.|Lab Medicine & Biochemistry, Nayati Multi super speciality Hospital, Mathura, 281003, U.P, India. nibhriti@hotmail.com.
authors.forename: Nibhriti
authors.initials: N
authors.lastname: Das
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D018958:CD55 Antigens / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018958:CD55 Antigens; D016207:Cytokines
keywords: Circulating PBMCs; Complement regulatory protein; Cytokines; DAF; DAS28; Rheumatoid arthritis