Asymptomatic Dengue Infection in a Cuban Population Confirms the Protective Role of the RR Variant of the FcγRIIa Polymorphism

Abstract

Abstract. The role of human Fcγ receptors (FcγR) has been recognized considerably over the last years. These receptors vary in their affinity for IgG subclasses and the intracellular signals elicited by them. Allelic variants of FcγR genes may influence the biological phagocyte activity, accounting for an inherited pre-disposition to disease. The specific FcγRIIa (CD32) contains a polymorphic variant (H/R131) that has been associated to a reduced risk for developing dengue hemorrhagic fever (DHF). Here, we investigated the role of this polymorphism in a very well-characterized group of Cuban individuals with antecedents of DHF, dengue fever (DF), or subclinical dengue infection. The HH131 genotype was significantly associated with dengue disease, either DF (* P = 0.016; odds ratio = 4.425; 95% confidence interval = 1.10-20.52) or DHF ( P = 0.00018; odds ratio = 10.56; 95% confidence interval = 2.33-54.64) with respect to the subclinical infection.

Human FcγRII Cytoplasmic Domains Differentially Influence Antibody-Mediated Dengue Virus Infection

“…Furthermore, the K562 FcgRIIa showed a bimorphic allotype at position 131 (H/R), thus minimizing any potential binding differences because IgG subclasses bind differently to human FcgRII allotypes/subtypes. The use of polyclonal antidengue serum for complexing with DENV2 was thought to minimize any potential binding differences because of IgG1-4 ligating FcgRII allotypes (11,29). We used small inhibitory RNAs or a specific mAb directed to human FcgRIIa to inhibit DENV ADE and confirm its important role in DV infection of K562 cells (Fig.…”

C‐Reactive Protein Triggers Calcium Signalling in Human Neutrophilic Granulocytes via FcγRIIa in an Allele‐Specific Way

“…The actual R131H-polymorphism of FccRIIa has been found relevant to receptivity to infectious diseases, such as dengue fever [45] and periodontitis [46], as well as autoimmune Grave's disease [47], systemic lupus erythematosus [48], rheumatoid arthritis [49] and type 1 diabetes [49]. It seems like the R/R131 allele increases the susceptibility to both bacterial infections and autoimmune diseases, whereas the H/H131 allele does not.…”

Association of FcγRIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan

“…Comparisons were made between subclinical group and one or both groups of clinical infections to determine any association of FcγRIIa H131R genotypes and clinical outcome of dengue infection by means of an odds ratio (OR), as exemplified in similar studies. 10,11 Logistic regression model was also generated to analyze the effect of FcγRIIa H131R genotypes on disease severity in the presence of other biological covariates. All the statistical analyses were performed using the SPSS version 20 software, Armonk NY.…”

“…9 A number of host genetic factors seem to be important in contributing toward variable susceptibility to severe dengue disease. Besides ethnicity, these include genetic variants in immune system receptor genes (especially, FcγRIIa and DC-SIGN), 10,11 major histocompatibility complex system genes, 8,[12][13][14] genes of complement pathway (e.g. MBL2), 15 cytokine genes (e.g.…”

“…Three previous studies from Vietnam, Cuba, and Mexico also support the involvement of FcγRIIa polymorphism in dengue pathogenesis. 10,11,18 It is speculated that dengue virus may have been endemic in Pakistan, but due to lack of any effective surveillance and diagnostic measures, no outbreaks were reported until 1994, when introduction of DENV-1 serotype caused a major outbreak in southern Pakistan with high morbidity and mortality rates. 23 After a gap of almost 10 years, dengue outbreaks ensued again in 2005/2006 claiming many deaths, 24 with circulating serotypes of DENV-2 and the new DENV-3 (New Delhi genotype).…”