Letter to the Editor: Immune Complex: Does It Have a Role in Pathogenesis of Renal Failure in Dengue Infection?

Abstract

Dengue infection is a major public health problem. When acute renal failure complicates dengue infection, it is usually associated with severe disease as in dengue hemorrhagic fever or dengue shock syndrome. The role of immune complex in development of renal failure in dengue infection is still unclear. Here, the author used a computational medicine technology to study the property of the dengue virus-immunoglobulin complex. According to this study, the diameter of derived complex is much smaller, compared with the diameter of glomerulus. Entrapment of the immune complex is believed to occur when a previous glomerular lesion causes narrowing of the glomerulus's diameter. Therefore, the immune complex should not have a significant role in pathogenesis of renal failure in dengue infection.

• dengue
• immune complex
• renal failure

Dengue infection is a major public health problem, yearly affecting thousands of children in the Southeast Asia region.[1] Luckily, the classical form of this infection resembles viral flu: fever, headache, chill, and rash. Mostly, affected patients had a complete recovery without any complication.[2] However, there is a severe form of dengue infection called dengue hemorrhagic fever. In this case, the host immunologic response host is the important factor in the course of disease.[3] These responses are immune complex formation, complement activation, increased histamine release, and a massive release of many cytokines into the circulation, leading to shock, vasculopathy, thrombopathy, and disseminated intravascular coagulation.[3]

When acute renal failure complicates dengue infection, it is usually associated with severe disease as in dengue hemorrhagic fever or dengue shock syndrome.[4] Development of renal failure in the absence of bleeding manifestations, extensive capillary leak, or circulatory failure is rare.[4] The role of immune complex in development of renal failure in dengue infection is still unclear. More recently, Boonpucknavig et al. described a patient with dengue fever who presented with a febrile illness and acute renal failure requiring dialysis, in the absence of features of hemorrhage or shock.[5] They proposed that immune complex-induced nephropathy might be the main corresponding underlying factor for renal failure in this case.[5] Although there are some reports mentioning the occurrence of immune complex in the glomerulus of some patients with dengue infection, the nature of that complex, which might not be dengue virus-immune complex, is not identified.[5]

Here, the author used a computational medicine technology to study the property of the dengue virus-immunoglobulin complex. A computational molecular technique, PatchDock,[6] was used to model the recombination. Briefly, PatchDock is a computational molecular technique for molecular docking based on shape complementarity principles.[6] The input is two molecules of any type: proteins, DNA, peptides, or drugs.[6] In this study, the input is the previously modeled dengue virus and immunoglobulin molecules.[7] The output, or result, was further processed to be in the format of molecular structure by Swiss-Pdb Viewer (GlaxoSmithKline R&D and the Swiss Institute of Bioinformatics). The property and geometry of the derived complex was also studied by the Swiss-Pdb Viewer.

According to this study, the geometric parameters of the derived dengue virus-immunoglobulin immune complex are 49 nm × 42 nm × 46 nm. Compared with the diameter of glomerulus (∼ 0.2 mm in diameter), the diameter of derived complex is much smaller. It seems that it is difficult that the formed immune complex in dengue infection can entrap in the glomerulus since the complex's size is smaller. Entrapment of the immune complex is believed to occur when a previous glomerular lesion causes narrowing of the glomerulus's diameter. Therefore, the immune complex should not have a significant role in pathogenesis of renal failure in dengue infection.