An Inflammatory Story: Antibodies in Tuberculosis Comorbidities.

Milla R. McLean,Amy W. Chung,Stephen J. Kent,Lenette L. Lu

doi:10.3389/fimmu.2019.02846

Abstract

Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with pro-inflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

Highlights

Mycobacterium tuberculosis (Mtb) is a leading cause of mortality and morbidity across the globe with an estimated 10 million new infections annually and a quarter of the world’s population infected [1]
With a quarter of the world latently infected with Mtb and the rise of noncommunicable diseases such as type 2 diabetes mellitus (T2DM) and Chronic Kidney Disease (CKD) in both developed and developing countries, we must pay attention to this double burden of disease
The paradoxical evidence around T cell responses and type 1 cytokines suggests that high IFNγ, TNF-α, and IL-2 CD4+ T cells induced in response to vaccination or before the establishment of TB disease is beneficial to TB control, but when these responses are too late or they expand after Mtb has established, they are detrimental

Summary

Introduction

Mycobacterium tuberculosis (Mtb) is a leading cause of mortality and morbidity across the globe with an estimated 10 million new infections annually and a quarter of the world’s population infected [1]. While monoclonal antibodies differ compared to polyclonal humoral immune responses in infection due to both antigen specificity and antibody glycosylation, these monoclonal studies suggest that IgA may mediate control of bacterial burden through both FcαR dependent and independent mechanisms. Upon the addition of purified polyclonal IgG after Mtb infection, intracellular bacterial burden is decreased in the context of antibodies from latent compared to active TB individuals [26].

Results

Conclusion