Abstract
HLA-B27 is the allele most frequently associated with human anterior uveitis. The majority of HLA-B27-positive [acute anterior uveitis (AAU)] patients develop clinically distinct symptoms with acute symptomatic onset of flare and a recurrent disease course characterized by a massive cellular ocular infiltrate during uveitis relapse. By contrast, uveitis in HLA-B27-negative [idiopathic anterior uveitis (IAU)] patients tends to develop a clinically less fulminant, more chronic, and typically asymptomatic disease course. To analyze systemic immune responses in the different uveitis entities, we analyzed peripheral blood cells by flow cytometry. In addition, as a pro-inflammatory biomarker serum, S100A8/A9 levels were quantified by ELISA from patients with AAU (n = 27) and IAU (n = 21), and in healthy controls (n = 30). Data were obtained either during active uveitis flare or after 3 months of inactivity. IAU patients showed a transiently increased frequency of CD56- and CD163-positive monocytes and of both granulocytic myeloid-derived suppressor cells and Th17 cells during active uveitis. By contrast, AAU patients showed an elevated frequency of monocytes, activated T cells, and elevated S100A8/A9 serum levels during clinically quiescent disease. The differentially regulated response of both innate and adaptive immune cells in the blood may be related to the clinically distinct characteristics of the two different uveitis entities.
Highlights
Uveitis describes an inflammatory phenotype within the eye globe that is classified into various anatomical subgroups [1]
Both the HLA-B27associated acute anterior uveitis (AAU) and HLA-B27-negative idiopathic anterior uveitis (IAU) patient groups included some ANA-positive individuals (22 or 9.5%, respectively), while rheumatoid factor (RF) positivity was only detected in the AAU group (11%)
Compared with the IAU patients, the S100A8/A9 level was significantly higher in the AAU cohort during uveitis inactivity. Monocytes and their diverse populations have received increased attention in autoimmune disease research [32,33,34]. An understanding of their plasticity and phenotype in relation to disease course may promote the development of novel treatment strategies for patients with different autoimmune diseases
Summary
Uveitis describes an inflammatory phenotype within the eye globe that is classified into various anatomical subgroups [1]. Anterior uveitis (AU) is defined as inflammation confined to the anterior eye segment, involving the iris and ciliary body. Non-infectious, acute anterior uveitis (AAU) associated with presence of the HLA-B27 allele is a well-defined entity and is one of the most common types of uveitis [2,3,4,5]. AAU is characterized by sudden onset, with typical clinical features including pain, eye redness, photophobia, and blurred vision. Characteristic signs of severe uveitis episodes include cellular infiltration and fibrin formation in the anterior chamber. Monocyte in HLA-B27-Positive and -Negative AU (AC) and spill-over of infiltrating cells into the anterior vitreous. Treatment of inflammation is mandatory for achieving inactivity, to prevent vision-threatening complications and severe burden of illness. In addition to topical or systemic corticosteroids, treatment modalities nowadays include disease-modifying anti-rheumatic drugs, such as synthetic, conventional, and/or biological drugs for steroid sparing
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