Why Do Diseases Start One Sided? Clues from Hla-b27 Acute Anterior Uveitis

Uveitis is an inflammatory disease with significant disease burden, as it causes ≤10% of legal blindness in the USA. Patients are usually affected in their prime working years. Even in those with good treatment response, quality of life is substantially compromised. The most common form of uveitis is acute anterior uveitis, and approximately half of these cases are associated with human leukocyte antigen B27 (HLA-B27). The typical clinical presentation is sudden onset of a red sore eye with white cells and protein leaking into the anterior chamber. There is inter-individual variance in clinical signs, with the most severe cell response appearing like a snowstorm in the anterior chamber, causing cells to pile up in a snowbank appearance called a hypopyon. One of the truly curious, yet pathognomonic, features is the tendency for the inflammatory response to have a unilateral presentation. Either the right or left eye can manifest obvious inflammation, yet the other eye is completely unaffected. Also, subsequent attacks may occur on the same or contralateral side. Clearly, the immune system is capable of distinguishing a molecular variance between the two eyes, but what this difference is remains a mystery. This article will review HLA-B27 uveitis plus its associated systemic diseases; additionally, various mechanisms that play a role in determining left–right disease asymmetry will be discussed. Establishing how the immune system makes this left–right decision will have relevance to understanding causes of asymmetry in other inflammatory, degenerative, and malignant disorders.