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Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future
Rohit Parthasarathy1, Fernando Santiago1, Peter McCluskey2
1School of Medical Sciences, Faculty of Medicine & Health, UNSW, Sydney, Australia.
Abstract:
The pathogenesis of human leukocyte antigen (HLA)-B27-associated diseases such as acute anterior uveitis (AAU) and ankylosing spondylitis (AS) remains poorly understood, though Gram-negative bacteria and subclinical bowel inflammation are strongly implicated. Accumulating evidence from animal models and clinical studies supports several hypotheses, including HLA-B27-dependent dysbiosis, altered intestinal permeability, and molecular mimicry. However, the existing literature is hampered by inadequate studies designed to establish causation or uncover the role of viruses and fungi. Moreover, the unique disease model afforded by AAU to study the gut microbiota has been neglected. This review critically evaluates the current literature and prevailing hypotheses on the link between the gut microbiota and HLA-B27-associated disease. We propose a new potential role for HLA-B27-driven altered antibody responses to gut microbiota in disease pathogenesis and outline recommendations for future well-controlled human studies, focusing on AAU.
Insights
The gut microbiome
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Human leukocyte antigen (HLA)-B27 is linked to diseases like acute anterior uveitis (AAU) and ankylosing spondylitis (AS).
- The exact mechanisms driving these HLA-B27-associated diseases are not fully understood, despite evidence implicating gut bacteria and inflammation.
- Current research often lacks the robust design needed to confirm causation or explore roles of viruses and fungi.
Purpose of the Study:
- To critically review existing literature and hypotheses on the gut microbiota's role in HLA-B27-associated diseases.
- To highlight the understudied potential of acute anterior uveitis (AAU) as a model for gut microbiota research.
- To propose novel hypotheses regarding HLA-B27's influence on immune responses to gut microbes.
Main Methods:
- Literature review and critical evaluation of current research.
- Analysis of existing hypotheses, including dysbiosis, intestinal permeability, and molecular mimicry.
- Synthesis of evidence from animal models and human clinical studies.
Main Results:
- Existing studies have limitations in establishing causality and exploring diverse microbial roles (viruses, fungi).
- The gut microbiota is strongly implicated, but specific mechanisms remain unclear.
- Acute anterior uveitis (AAU) offers a unique, yet neglected, model for studying gut microbiota's role.
Conclusions:
- Future research should focus on well-controlled human studies, particularly in AAU.
- Investigating HLA-B27-driven altered antibody responses to gut microbiota is a promising new direction.
- A comprehensive understanding requires exploring a broader range of microbial agents and host-microbe interactions.
